Origin/Distribution
Aji Charapita chile peppers are native to the northern Peruvian jungles in a city named Iquitos and have been cultivated on a local scale since ancient times. Thriving in warm climates, Charapita peppers are grown predominately wild and have only recently been cultivated for commercial use.
description/taste
Aji Charapita chile peppers are very small, averaging 5-8 millimeters in diameter, and have a round to ovate shape with a slender, straight green stem protruding from the pod. The petite peppers have thin, glossy, and smooth skin, transforming from green to yellow when mature. Underneath the skin, the flesh is yellow, firm, and crisp, encasing a cluster of tiny, cream-colored seeds. Aji Charapita chile peppers have a bright, fruity taste with unique citrus flavors that are followed by a moderate to hot level of spice that gradually builds in intensity.
CURRENT FACTS
Aji Charapita chile peppers, botanically classified as Capsicum chinense, are tiny pods that grow on wide and bushy plants reaching over one meter in height and are members of the Solanaceae or nightshade family. Also known as Wild Peruvian Chili, Tettinas de Monk, Charapilla, and Aji Charapa, Aji Charapita chile peppers are considered to be one of the most expensive peppers in the world. Native to the jungles of northern Peru, Aji Charapita peppers have a strong heat, ranging 30,000-50,000 SHU on the Scoville scale, and have recently increased in popularity for their fruity flavor. Despite their global recognition, the tiny peppers are not widely sourced outside of Peru, making them a rare and expensive variety, and are also considered to be one of the more costly spices when dried and ground, similarly to vanilla and saffron.
agroecology
Ají charapita is a variety of chili pepper (it belongs to the Capsicum genus) found especially in the north of the Peruvian forest and is one of the five varieties that are grown in the country.
It originates from the cities of Iquitos and Pucallpa and now grows especially in the Departamentos of Ucayali, Loreto and Madre de Dios.
The plant grows preferably in areas with a hot climate, high humidity and soils with a high quantity of organic matter. In ideal conditions, it can reach a height of one meter and develop a rich foliage with oval shaped, light green leaves. Seeds are sown in winter, while the fruits are harvested in summer.
The plant begins to bear fruits after 60-120 days since the transplant and can continue to produce them for up to two months, depending on the area and climate. It is productive for six years, although the amount of fruits drops over the years.
The ají charapita pepper has a very peculiar aspect: it is small and rounded (it looks like a small yellow pea) and it is usually yellow, although it can also be green or yellow, depending on the ecotype.
This Capsicum stands out for the high content of capsaicin, which makes it decidedly hot: it is considered one of the hottest chilies in Peru.
It has a fundamental role in Amazonian cooking, particularly in the province of Coronell Portillo, as it is the basic ingredient of many traditional dishes.
Despite its importance in the local cuisine, it is not very well known and used in the rest of Peru, also because it is difficult to find.
It originates from the cities of Iquitos and Pucallpa and now grows especially in the Departamentos of Ucayali, Loreto and Madre de Dios.
The plant grows preferably in areas with a hot climate, high humidity and soils with a high quantity of organic matter. In ideal conditions, it can reach a height of one meter and develop a rich foliage with oval shaped, light green leaves. Seeds are sown in winter, while the fruits are harvested in summer.
The plant begins to bear fruits after 60-120 days since the transplant and can continue to produce them for up to two months, depending on the area and climate. It is productive for six years, although the amount of fruits drops over the years.
The ají charapita pepper has a very peculiar aspect: it is small and rounded (it looks like a small yellow pea) and it is usually yellow, although it can also be green or yellow, depending on the ecotype.
This Capsicum stands out for the high content of capsaicin, which makes it decidedly hot: it is considered one of the hottest chilies in Peru.
It has a fundamental role in Amazonian cooking, particularly in the province of Coronell Portillo, as it is the basic ingredient of many traditional dishes.
Despite its importance in the local cuisine, it is not very well known and used in the rest of Peru, also because it is difficult to find.
edible plants and uses
The fruit of this species is smaller but more pungent than C. annuum and the uses are similar. It is employed as a spice flavouring in many foods.
botany
Small, branched, mostly erect, annual or shortlived perennial sub-shrub, 30–100 cm tall with a short or deep tap root and sparsely pubescent to glabrascent stem. Leaves simple, alternate, ovate to broadly lanceolate, 2.5–7 cm long, 1.5–3 cm wide, margins entire, apex acute to acuminate, base subcuneate, oblique (Plates 1 – 4 ), petioles narrowly winged above, 0.8–2 cm long. Flowers more commonly 2–4 per axil, pedicels 1–2.5 cm long, stout in fruit, erect; calyx cupular, truncate, 3–4 mm long, the lobes minute; corolla greenish white or greenish yellow, waxy, divided ca. 1/2 to base, the lobes triangular, ca. 1.5 cm in diameter; stamens 5, inserted toward base of corolla tube; fi laments ca. 1–2 mm long; anthers bluish, oblong. Berry, pungent, ellipsoid-conical to lanceoloid or fusiform, 10–20 mm long, 3–7 mm in diameter, much smaller and narrower than C. annuum , pericarp fl eshy and fi rm, hollow, green when young to mostly red or orange when mature and 5 by 1 cm and erect (pointing upwards) (Plates 1 – 4 ). Seeds yellowish, fl attened-lenticular, 3–5 mm long.
Nutritive/Medicinal Properties
The proximate nutrient value per 100 g edible portion of C. frutescens (Chilli padi) fruit was reported by Tee et al. ( 1997 ) as follows:
Proximate nutrient composition of hot chilli pepper per 100 g edible portion was reported by USDA ( 2012 ) as:
Fatty acids and hydrocarbons were the main chemical components of the volatile oil from Capsicum frutescens var. conoides from Guizhou, Guangxi, Sichuan and Hubei; other components included :
The oils also contained :
The volatile organic compounds found in the cayenne fruit of C. frutescens included :
Eighty- five volatile organic components were identified and quantified in a native Chinese chilli pepper ( Capsicum frutescens ) variety (Liu et al. 2009 ) .
Forty compounds were found at the green stage, fifty-three at the breaking stage and sixty- five at the red colour stage.
The amount of alkenes and aldehydes increased from 2.762 and 0.120% in green stage to 11.137 and 14.485% in the coloured stage.
The content of alcohols decreased from 30.169 to 23.698%.
The aromatic compound disappeared during maturity.
Ketones were enhanced from 0.983 to 2.693% while esters declined during maturity.
One-hundred-seventytwo volatile compounds were identified in three Colombian cultivars of Capsicum frutescens representing 30.26, 22.36 and 68.26 mg/kg for Cesari amarillo, Cesari morado and Pajarito cultivars, respectively (Quijano and Pino 2010 ) .
while in the Pajarito cultivar the majors were :
More than 300 volatile constituents were detected in the ripe fruits of 16 Capsicum accessions from the annuum-chinense-frutescens complex (Rodríguez-Burruezo et al. 2010 ) .
Esters and terpenoids were the main groups, although other minor compounds, such as nitrogen and sulfur compounds, phenol derivatives, norcarotenoids, lipoxygenase derivatives, carbonyls, alcohols, and other hydrocarbons, were also identified.
The sniffing test revealed that the diversity of aromas found among the studied cultivars was due to qualitative and quantitative differences of, at least, 23 odour-contributing volatiles (OCVs).
C. chinense , and C. frutescens accessions, with fruity/exotic aromas, were characterized by a high contribution of several esters and ionones and a low or nil contribution of green/vegetable OCVs.
Different combinations of fruity/exotic and green/vegetable OCVs would explain the range of aroma impressions found among C. annuum accessions. A total of 83 compounds, mostly esters and alcohols, were identified in the malagueta chilli pepper ( Capsicum frutescens ) (Junior et al. 2012 ) .
The following capsaicinoids having a common structure composed of a vanillyl amide moiety and C9–C11 branched fatty acids were extracted from Capsicum spp fruits:
The “heat” of chili peppers is directly related to the concentration of capsaicinoids, and it is evaluated by means of the organoleptical “Scoville Scale”. Pure capsaicin tops this scale with a rating of 16,000,000.
Eight capsaicinoids, pungent secondary metabolites were found in various parts of the pepper fruit (pericarp, placenta, seeds, and in the top, middle, and base parts of whole peppers) in 17 species of Capsicum peppers and in 23 peppercontaining foods (Kozukue et al. 2005 ) .
The compounds were:
The concentration found ranged from 0.5 to 3,600 m g of capsaicin equivalent/g of product.
Total phenol content was correlated with ascorbic acid (R 2 = 0.97) and free sugars (R 2 = 0.80) in the Capsicum germplasm tested that included :
Concentrations of total phenols (1.4, 1.3, and 1.3 mg/g fruit) and ascorbic acid (1.6, 1.2, and 1.3 mg/g fruit) were significantly greater in PI-633757, PI-387833, and PI-633754, respectively, compared to other accessions analyzed.
Total capsaicinoids concentrations were greatest (1.3 mg/g fruit) in PI-438622 and lowest (0.002 mg/g fruit) in Grif-9320.
Capsaicin and dihydrocapsaicin were the dominant capsaicinoids detected in methanol extract of fresh fruits of:
Capsaicin concentrations were typically greater than dihydrocapsaicin.
Concentrations of total capsaicinoids varied from not detectable to 11.2 mg/fruit.
Statistical analysis revealed that accession :
Ten cultivars out of 35 cultivars tested: 18 cultivars of C. annuum , 7 of C. baccatum , 5 of C. chinense , 4 of C. frutescens , and 1 of C. pubescens contained capsiconinoids (Tanaka et al. 2009 ) .
Capsiconinoid Baccatum (CCB) ( C. baccatum var. praetermissum ) showed the highest capsiconinoid content (3,314 m g/g DW) and Charapita ( C. chinense ) had the second highest content. The other eight cultivars had much lower capsiconinoid content than these two cultivars (<300 m g/g DW).
Capsiconinoids had been reported to have agonist activity for transient receptor potential vanilloid type 1 (TRPV1).
Forty-nine samples representing distinct morphotypes of four cultivated species ( C. annuum var. annuum, C. annuum var. glabriusculum, C. baccatum , C. chinense , and C. frutescens ) were found to contain detectable levels (11–369 m g/g) of a capsinoid, E-capsiate (Singh et al. 2009 ) .
Nine of the E-capsiate-containing samples also had dihydrocapsiate (18–86 m g/g).
Two new glucosides:
The glucosides were also detected in various pungent cultivars of C. annuum , Capsicum frutescens , and Capsicum chinense .
However, they were not detected in non-pungent cultivars of C. annuum . Additionally, a positive correlation was observed between the quantity of the capsaicinoids, capsaicin, and dihydrocapsaicin and their glucosides. C. frutescens leaf was found to contain 95.4 mg/ kg of a -tocopherol (Ching and Mohamed 2001 ) .
Capsaicinoids such as :
Capsaicinoids may have bene fits on cardiovascular and gastrointestinal system and may also have potential value in clinic for pain relief, cancer prevention and weight loss.
They had been shown to be potential agonists of capsaicin receptor or transient receptor potential vanilloid subfamily member 1 (TRPV1). They could exert effects through the receptor-dependent and receptor-independent pathways.
- water 81.5,
- energy 47 kcal,
- protein 3.9 g,
- fat 0.7 g,
- ash 6.04 g,
- carbohydrate 6.2 g,
- dietary fibre 7.0 g,
- ash 1.2 10.34 g,
- Ca 39 mg,
- P 118 mg,
- Fe 1.2 mg,
- K 544 mg,
- Na 35 mg,
- Mg 42 mg,
- Cu 0.13 mg,
- Zn 0.5 mg,
- carotenes 1,336 m g,
- retinol equivalent 228 m g,
- vitamin B1 0.30 mg,
- vitamin B2 0.20 mg,
- niacin 2.0 mg and
- vitamin C 54.8 mg.
Proximate nutrient composition of hot chilli pepper per 100 g edible portion was reported by USDA ( 2012 ) as:
- water 88.02 g,
- energy 40 kcal (166 kJ),
- protein 1.87 g,
- total lipid 0.44 g,
- ash 0.87 g,
- carbohydrate 8.81 g,
- total dietary fibre 1.5 g,
- total sugars 5.30 g,
- Ca 14 mg,
- Fe 1.03 mg,
- Mg 23 mg,
- P 43 mg, K 322 mg,
- Na 9 mg,
- Zn 0.26 mg,
- Cu 0.129 mg,
- Mn 0.187 mg,
- Se 0.5 m g,
- vitamin C 143.7 mg,
- thiamin 0.072 mg,
- niacin 1.244 mg,
- ribo flavin 0.086 mg,
- pantothenic acid 0.201 mg,
- vitamin B-6 0.506 mg,
- total folate 23 m g,
- total choline 10.9 mg,
- vitamin A 48 m g RAE,
- vitamin A 952 IU,
- b -carotene 534 m g,
- a -carotene 36 m g,
- b -cryptoxanthin 40 m g,
- lutein + zeaxanthin 709 m g,
- vitamin E ( a -tocopherol) 0.69 mg,
- vitamin K (phylloquinone) 14.0 m g,
- 14:0 (myristic acid) 0.002 g,
- 16:0 (palmitic acid) 0.033 g,
- 18:0 (stearic acid) 0.007 g,
- total monounsaturated fatty acids 0.024 g,
- 18:1 undifferentiated (oleic acid) 0.024 g,
- total polyunsaturated fatty acids 0.239 g,
- 18:2 undifferentiated (linoleic acid) 0.228 g,
- 18:3 undifferentiated (linolenic acid) 0.011 g,
- tryptophan 0.026 g,
- threonine 0.074 g,
- isoleucine 0.065 g,
- leucine 0.105 g,
- lysine 0.089 g,
- methionine 0.024 g,
- cystine 0.038 g,
- phenylalanine 0.062 g,
- tyrosine 0.042 g,
- valine 0.084 g,
- arginine 0.096 g,
- histidine 0.041 g,
- alanine 0.082 g,
- aspartic acid 0.286 g,
- glutamic acid 0.264 g,
- glycine 0.074 g,
- proline 0.087 g and
- serine 0.080 g.
Fatty acids and hydrocarbons were the main chemical components of the volatile oil from Capsicum frutescens var. conoides from Guizhou, Guangxi, Sichuan and Hubei; other components included :
- esters,
- ketones,
- acylamines and
- aldehydes
The oils also contained :
- 48–74.52% capsaicin,
- 2.83–2.87% vitamin E.
The volatile organic compounds found in the cayenne fruit of C. frutescens included :
- sesquiterpenes ( d -elemene, a -humelene, g -himachalene, b -bisabolene)
- different monoterpenes /monoterpenoids and
- members of different classes of metabolites
Eighty- five volatile organic components were identified and quantified in a native Chinese chilli pepper ( Capsicum frutescens ) variety (Liu et al. 2009 ) .
Forty compounds were found at the green stage, fifty-three at the breaking stage and sixty- five at the red colour stage.
The amount of alkenes and aldehydes increased from 2.762 and 0.120% in green stage to 11.137 and 14.485% in the coloured stage.
The content of alcohols decreased from 30.169 to 23.698%.
The aromatic compound disappeared during maturity.
Ketones were enhanced from 0.983 to 2.693% while esters declined during maturity.
One-hundred-seventytwo volatile compounds were identified in three Colombian cultivars of Capsicum frutescens representing 30.26, 22.36 and 68.26 mg/kg for Cesari amarillo, Cesari morado and Pajarito cultivars, respectively (Quijano and Pino 2010 ) .
- Isohexyl isohexanoate,
- Isohexyl isovalerate and
- isohexyl 2-methylbutyrate
while in the Pajarito cultivar the majors were :
- isohexyl isovalerate and
- hexyl isovalerate.
More than 300 volatile constituents were detected in the ripe fruits of 16 Capsicum accessions from the annuum-chinense-frutescens complex (Rodríguez-Burruezo et al. 2010 ) .
Esters and terpenoids were the main groups, although other minor compounds, such as nitrogen and sulfur compounds, phenol derivatives, norcarotenoids, lipoxygenase derivatives, carbonyls, alcohols, and other hydrocarbons, were also identified.
The sniffing test revealed that the diversity of aromas found among the studied cultivars was due to qualitative and quantitative differences of, at least, 23 odour-contributing volatiles (OCVs).
C. chinense , and C. frutescens accessions, with fruity/exotic aromas, were characterized by a high contribution of several esters and ionones and a low or nil contribution of green/vegetable OCVs.
Different combinations of fruity/exotic and green/vegetable OCVs would explain the range of aroma impressions found among C. annuum accessions. A total of 83 compounds, mostly esters and alcohols, were identified in the malagueta chilli pepper ( Capsicum frutescens ) (Junior et al. 2012 ) .
The following capsaicinoids having a common structure composed of a vanillyl amide moiety and C9–C11 branched fatty acids were extracted from Capsicum spp fruits:
- 440 m g/g capsaicin,
- 81 m g/g dihydrocapsaicin, and
- 11 m g/g nordihydrocapsaicin
The “heat” of chili peppers is directly related to the concentration of capsaicinoids, and it is evaluated by means of the organoleptical “Scoville Scale”. Pure capsaicin tops this scale with a rating of 16,000,000.
Eight capsaicinoids, pungent secondary metabolites were found in various parts of the pepper fruit (pericarp, placenta, seeds, and in the top, middle, and base parts of whole peppers) in 17 species of Capsicum peppers and in 23 peppercontaining foods (Kozukue et al. 2005 ) .
The compounds were:
- capsaicin,
- dihydrocapsaicin,
- homocapsaicin-I,
- homocapsaicin-II,
- homodihydrocapsaicin-I,
- homodihydrocapsaicin-II,
- nonivamide, and
- nordihydrocapsaicin.
The concentration found ranged from 0.5 to 3,600 m g of capsaicin equivalent/g of product.
Total phenol content was correlated with ascorbic acid (R 2 = 0.97) and free sugars (R 2 = 0.80) in the Capsicum germplasm tested that included :
- four accessions of Capsicum chinense ;
- five accessions of C. baccatum ;
- six accessions of C. annuum ; and
- two of C. frutescens
Concentrations of total phenols (1.4, 1.3, and 1.3 mg/g fruit) and ascorbic acid (1.6, 1.2, and 1.3 mg/g fruit) were significantly greater in PI-633757, PI-387833, and PI-633754, respectively, compared to other accessions analyzed.
Total capsaicinoids concentrations were greatest (1.3 mg/g fruit) in PI-438622 and lowest (0.002 mg/g fruit) in Grif-9320.
Capsaicin and dihydrocapsaicin were the dominant capsaicinoids detected in methanol extract of fresh fruits of:
- Capsicum chinense ,
- C. frutescens ,
- C. baccatum ,
- C. annuum , and
- C. pubescens
Capsaicin concentrations were typically greater than dihydrocapsaicin.
Concentrations of total capsaicinoids varied from not detectable to 11.2 mg/fruit.
Statistical analysis revealed that accession :
- PI-441624 ( C. chinense ) had the highest capsaicin content (2.9 mg/g fresh fruit) and accession
- PI-497984 ( C. frutescens ) had the highest dihydrocapsaicin content (2.3 mg/g fresh fruit). Accessions
- PI-439522 ( C. frutescens ) and
- PI-497984 contained the highest concentrations of total capsaicinoids.
Ten cultivars out of 35 cultivars tested: 18 cultivars of C. annuum , 7 of C. baccatum , 5 of C. chinense , 4 of C. frutescens , and 1 of C. pubescens contained capsiconinoids (Tanaka et al. 2009 ) .
Capsiconinoid Baccatum (CCB) ( C. baccatum var. praetermissum ) showed the highest capsiconinoid content (3,314 m g/g DW) and Charapita ( C. chinense ) had the second highest content. The other eight cultivars had much lower capsiconinoid content than these two cultivars (<300 m g/g DW).
Capsiconinoids had been reported to have agonist activity for transient receptor potential vanilloid type 1 (TRPV1).
Forty-nine samples representing distinct morphotypes of four cultivated species ( C. annuum var. annuum, C. annuum var. glabriusculum, C. baccatum , C. chinense , and C. frutescens ) were found to contain detectable levels (11–369 m g/g) of a capsinoid, E-capsiate (Singh et al. 2009 ) .
Nine of the E-capsiate-containing samples also had dihydrocapsiate (18–86 m g/g).
Two new glucosides:
- capsaicin- b -D-glucopyranoside (1) and
- dihydrocapsaicin- b -D-glucopyranoside (2),
The glucosides were also detected in various pungent cultivars of C. annuum , Capsicum frutescens , and Capsicum chinense .
However, they were not detected in non-pungent cultivars of C. annuum . Additionally, a positive correlation was observed between the quantity of the capsaicinoids, capsaicin, and dihydrocapsaicin and their glucosides. C. frutescens leaf was found to contain 95.4 mg/ kg of a -tocopherol (Ching and Mohamed 2001 ) .
Capsaicinoids such as :
- dihydrocapsaicin,
- nordihydrocapsaicin,
- homodihydrocapsaicin, and
- homocapsaicin, etc.
- analgesic,
- anticancer,
- antiinflammatory,
- antioxi-dant,
- anti-obesity (Luo et al. 2011 ) ,
- antidiabetic, and
- hypolipidemic/antihypercholesterolemic activities.
Capsaicinoids may have bene fits on cardiovascular and gastrointestinal system and may also have potential value in clinic for pain relief, cancer prevention and weight loss.
They had been shown to be potential agonists of capsaicin receptor or transient receptor potential vanilloid subfamily member 1 (TRPV1). They could exert effects through the receptor-dependent and receptor-independent pathways.
antioxidant activity
Capsicum annuum, Capsicum frutescens, and Capsicum chinense peppers were found to contain high levels of
L-ascorbic acid and carotenoids at maturity, contributing 124–338% of theRDA (Recommended Daily Allowance) for
vitamin C and 0.33–336 RE/100 g of provitamin A activity, respectively (Howard et al. 2000 ) .
Levels of phenolic acids, capxanthin, and zeaxanthin generally increased during maturation, whereas the level of lutein declined.
Flavonoid concentrations varied greatly among the pepper types analyzed and were negatively correlated to
antioxidant activity under the conditions of the β-carotene-linoleic assay. Significant increases in antioxidant activity were observed in pepper juice models in response to increasing dilution factors and the presence of EDTA, indicating a pro-oxidant effect due to metal ions in the system.
In-vitro models demonstrated that increasing levels of flavonoids in combination with constant levels of caffeic and ascorbic acid gave a resultant antioxidant activity that was either additive of the two compounds or competitive in their ability to scavenge peroxyl radicals.
Studies showed that dietary hot short pepper ( Capsicum frutescens L. var. abbreviatum ) could prevent cyclophosphamide-induced oxidative stress in brain; although the pericarp ( flesh) being a better protectant than the seeds (Oboh and Ogunruku 2010 ) .
The higher inhibition of oxidative stress in brain (decrease in malondialdehyde level) and serum enzymes serum glutamate oxaloacetate transaminase (SGOT),
glutamate pyruvate transaminase (SGPT),
alkaline phos-phatase and metabolites (total bilirubin) by the flesh could be attributable to its significantly
higher total phenol content, reducing power and free-radical scavenging ability.
Dietary curcumin and capsaicin separately significantly inhibited the in-vivo iron-induced low-density lipoprotein (LDL) oxidation, as well as copper-induced oxidation of LDL in-vitro (Manjunatha and Srinivasan 2006 ) .
The protective effect of the combination of curcumin and capsaicin on LDL oxidation was greater than that
of individual compounds. This protective influence of spice principles was also indicated by the relative anodic electrophoretic mobility of oxidized LDL on agarose gel.
They also reported that rats injected with iron showed hepatic toxicity as measured by an increase in lipid peroxides
and elevated serum enzymes, alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase.
The activities of these enzymes, and the liver lipid peroxide level were reduced by dietary curcumin, capsaicin and their combination, indicating amelioration of the severity of iron-induced hepatotoxicity.
L-ascorbic acid and carotenoids at maturity, contributing 124–338% of theRDA (Recommended Daily Allowance) for
vitamin C and 0.33–336 RE/100 g of provitamin A activity, respectively (Howard et al. 2000 ) .
Levels of phenolic acids, capxanthin, and zeaxanthin generally increased during maturation, whereas the level of lutein declined.
Flavonoid concentrations varied greatly among the pepper types analyzed and were negatively correlated to
antioxidant activity under the conditions of the β-carotene-linoleic assay. Significant increases in antioxidant activity were observed in pepper juice models in response to increasing dilution factors and the presence of EDTA, indicating a pro-oxidant effect due to metal ions in the system.
In-vitro models demonstrated that increasing levels of flavonoids in combination with constant levels of caffeic and ascorbic acid gave a resultant antioxidant activity that was either additive of the two compounds or competitive in their ability to scavenge peroxyl radicals.
Studies showed that dietary hot short pepper ( Capsicum frutescens L. var. abbreviatum ) could prevent cyclophosphamide-induced oxidative stress in brain; although the pericarp ( flesh) being a better protectant than the seeds (Oboh and Ogunruku 2010 ) .
The higher inhibition of oxidative stress in brain (decrease in malondialdehyde level) and serum enzymes serum glutamate oxaloacetate transaminase (SGOT),
glutamate pyruvate transaminase (SGPT),
alkaline phos-phatase and metabolites (total bilirubin) by the flesh could be attributable to its significantly
higher total phenol content, reducing power and free-radical scavenging ability.
Dietary curcumin and capsaicin separately significantly inhibited the in-vivo iron-induced low-density lipoprotein (LDL) oxidation, as well as copper-induced oxidation of LDL in-vitro (Manjunatha and Srinivasan 2006 ) .
The protective effect of the combination of curcumin and capsaicin on LDL oxidation was greater than that
of individual compounds. This protective influence of spice principles was also indicated by the relative anodic electrophoretic mobility of oxidized LDL on agarose gel.
They also reported that rats injected with iron showed hepatic toxicity as measured by an increase in lipid peroxides
and elevated serum enzymes, alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase.
The activities of these enzymes, and the liver lipid peroxide level were reduced by dietary curcumin, capsaicin and their combination, indicating amelioration of the severity of iron-induced hepatotoxicity.
Antimicrobial Activity
A. fumigatus, A. parasiticus and A. niger with species-dependent LD 90 values between 3 and 20 m M. In vitro assays, CAY-1 was effective against Pneumocystis carinii (IC 50 : 9.5 m M) and Candida albicans (IC 90 : 6.2 m M).
It had no effect on the viability of the non-germinating conidia of the two filamentous fungi, P. carinii and C.
albicans , nor on the conidial type of Fusarium oxysporum .
It was ineffective against the bacteria Enterobacter agglomerans, Bacillus subtilis, Escherichia coli and Staphylococcus aureus .
CAY-1 was active against 16 different fungal strains, including Candida spp. and Aspergillus fumigatus [minimum inhibitory concentrations (MIC) ranging from 4 to 16 m g/mL], and was especially active against Cryptococcus neofor-
mans (90% inhibition at 1 m g mL) (Renault et al. 2003 ) .
Synergistic activity was also observed between CAY-1 and amphotericin B against Candida albicans and A. fumigatus . CAY-1 appeared to act by disrupting the membrane integrity of fungal cells.
CAY-1 exhibited predominantly additive-synergistic interaction with amphotericin B or itraconazole against the
nongerminated and germinating conidia of three Aspergillus species and Candida albicans ( De
Lucca et al. 2006a ) .
The results suggested CAY-1 enhanced amphotericin B and itraconazole efficacy. They also found that CAY-1 exhibited
antifungal activity against non-germinating conidia and hyphae of clinical isolates of the dermatophytes Trichophyton mentagrophytes, T. rubrum, T. tonsurans and Microsporum canis (Stergiopoulou et al. 2008 ) .
The minimal inhibitory concentrations (complete visual growth inhibition) of CAY-1 against non-germinating conidia
ranged from 10 to 20 m g/mL for all dermatophyte isolates It exhibited found >90% inhibition of hyphal metabolic activity of these same isolates at 10–20 m g/mL. In another paper, De Lucca et al. (2006b ) .
Reported on the purification of two antifungal steroidal saponins with same steroidal moiety but differ in the number of glucose moieties from cayenne pepper ( Capsicum frutescens ).
The first saponin had four glucose moieties (molecular mass 1,081 Da) and the second contained three glucose moieties (molecular mass 919 Da). The larger saponin was slightly fungicidal against the nongerminated and germinating conidia of Aspergillus fl avus, A. niger, A. parasiticus, A. fumigatus, Fusarium oxysporum, F. moniliforme ,
and F. graminearum , whereas, the second smaller saponin was inactive against these fungi.
The methanolic leaf extract of Capsicum frutescens var. longum showed dose dependent antibacterial and anthelmintic activity (Vinayaka et al. 2010 ) .
Among the bacteria studied, Staphylococcus aureus was found to be more susceptible to the methanolic extract followed by Klebsiella pneumoniae and Pseudomonas aeruginosa . The anthelmintic effect of all concentra-
tions was lesser when compared to the standard.
It had no effect on the viability of the non-germinating conidia of the two filamentous fungi, P. carinii and C.
albicans , nor on the conidial type of Fusarium oxysporum .
It was ineffective against the bacteria Enterobacter agglomerans, Bacillus subtilis, Escherichia coli and Staphylococcus aureus .
CAY-1 was active against 16 different fungal strains, including Candida spp. and Aspergillus fumigatus [minimum inhibitory concentrations (MIC) ranging from 4 to 16 m g/mL], and was especially active against Cryptococcus neofor-
mans (90% inhibition at 1 m g mL) (Renault et al. 2003 ) .
Synergistic activity was also observed between CAY-1 and amphotericin B against Candida albicans and A. fumigatus . CAY-1 appeared to act by disrupting the membrane integrity of fungal cells.
CAY-1 exhibited predominantly additive-synergistic interaction with amphotericin B or itraconazole against the
nongerminated and germinating conidia of three Aspergillus species and Candida albicans ( De
Lucca et al. 2006a ) .
The results suggested CAY-1 enhanced amphotericin B and itraconazole efficacy. They also found that CAY-1 exhibited
antifungal activity against non-germinating conidia and hyphae of clinical isolates of the dermatophytes Trichophyton mentagrophytes, T. rubrum, T. tonsurans and Microsporum canis (Stergiopoulou et al. 2008 ) .
The minimal inhibitory concentrations (complete visual growth inhibition) of CAY-1 against non-germinating conidia
ranged from 10 to 20 m g/mL for all dermatophyte isolates It exhibited found >90% inhibition of hyphal metabolic activity of these same isolates at 10–20 m g/mL. In another paper, De Lucca et al. (2006b ) .
Reported on the purification of two antifungal steroidal saponins with same steroidal moiety but differ in the number of glucose moieties from cayenne pepper ( Capsicum frutescens ).
The first saponin had four glucose moieties (molecular mass 1,081 Da) and the second contained three glucose moieties (molecular mass 919 Da). The larger saponin was slightly fungicidal against the nongerminated and germinating conidia of Aspergillus fl avus, A. niger, A. parasiticus, A. fumigatus, Fusarium oxysporum, F. moniliforme ,
and F. graminearum , whereas, the second smaller saponin was inactive against these fungi.
The methanolic leaf extract of Capsicum frutescens var. longum showed dose dependent antibacterial and anthelmintic activity (Vinayaka et al. 2010 ) .
Among the bacteria studied, Staphylococcus aureus was found to be more susceptible to the methanolic extract followed by Klebsiella pneumoniae and Pseudomonas aeruginosa . The anthelmintic effect of all concentra-
tions was lesser when compared to the standard.
antidiabetic activity
Studies found that capsaicin caused a decrease in blood glucose levels of 4.91 (n = 6) mmol/dl versus 6.40 mmol/dl(n = 6) for the control at the 2.5 h time interval when the oral glucose tolerance test (OGTT) was performed on dogs treated with capsaicin and compared with the control (Tolan et al. 2001 ) .
Also there was an increase in plasma insulin levels of 5.78 m IU/mL (n = 6) for the capsaicin treated dogs versus 3.70 m IU/mL (n = 10) for the control. Insulin receptor studies on monocytes showed that there was a decrease in the percentage receptor binding for the capsaicin treated dogs when compared with the control. insulin receptor calculations showed a decrease in number, 2.63 × 10(8) × 10(7), compared with 8.77 × 10(8) × 10(8) for the control.
The data showed insulin to be responsible for the hypoglycaemic episodes seen in the dogs and that it also caused an increase in insulin secretion which led to a reduction of insulin binding on the insulin receptors. The hypoglycaemic principle, capsaicin in C. frutescens was isolated and purified.
Purified capsaicin caused a decrease in blood glucose levels at 2.5 h in an OGTT in dogs with a concomitant elevation in plasma insulin levels (Tolan et al. 2004 ) .
Studies in healthy Thai women found that within 30 min after consumption of 5 g of fresh Capsicum frutescens , plasma glucose level during the absorption period was significantly inhibited.
The metabolic rate was also immediately increased after ingestion and this thermogenic effect was sustained up to 30 min (Chaiyata et al. 2003 ) .
In a separate crossover study of 12 healthy volunteers, consumption of 5 g Capsicum frutescens , decreased plasma glucose levels as revealed by OGTT and maintained the insulin levels (Chaiyasit et al. 2009 ) .
The results suggested the potential clinical implications of C. frutescens in the management of type 2 diabetes.
Studies in streptozotocin induced type 2 diabetic male Sprague Dawley rats showed that after 4 weeks of feeding red chilli ( C. frutescens ) low (RCL, 0.5%) and red chilli high (RCH, 2.0%) the fasting blood glucose concentrations in both RC fed groups were not significantly different (Islam and Choi 2008 ) .
The serum insulin concentration was significantly increased in the RCH group compared with the diabetic control and RCL groups. Blood HbA1c, liver weight, liver glycogen and serum lipids were not in fluenced by the feeding of RC-containing diets.
The data suggested that 2% dietary RC was insulinotropic rather than hypoglycemic at least in the experimental condition. Rau et al. ( 2006 ) reported that several herbal extracts including C. frutescens were found to be most active in a concentration dependent manner in the activation of peroxisome proliferatoractivated receptors (PPAR) that play a pivotal role in lipid and glucose homeostasis.
Synthetic activators of PPARalpha ( fibrates) and PPARgamma (glitazones) are widely used for treatment of dislipidemia and diabetes, respectively.
Also there was an increase in plasma insulin levels of 5.78 m IU/mL (n = 6) for the capsaicin treated dogs versus 3.70 m IU/mL (n = 10) for the control. Insulin receptor studies on monocytes showed that there was a decrease in the percentage receptor binding for the capsaicin treated dogs when compared with the control. insulin receptor calculations showed a decrease in number, 2.63 × 10(8) × 10(7), compared with 8.77 × 10(8) × 10(8) for the control.
The data showed insulin to be responsible for the hypoglycaemic episodes seen in the dogs and that it also caused an increase in insulin secretion which led to a reduction of insulin binding on the insulin receptors. The hypoglycaemic principle, capsaicin in C. frutescens was isolated and purified.
Purified capsaicin caused a decrease in blood glucose levels at 2.5 h in an OGTT in dogs with a concomitant elevation in plasma insulin levels (Tolan et al. 2004 ) .
Studies in healthy Thai women found that within 30 min after consumption of 5 g of fresh Capsicum frutescens , plasma glucose level during the absorption period was significantly inhibited.
The metabolic rate was also immediately increased after ingestion and this thermogenic effect was sustained up to 30 min (Chaiyata et al. 2003 ) .
In a separate crossover study of 12 healthy volunteers, consumption of 5 g Capsicum frutescens , decreased plasma glucose levels as revealed by OGTT and maintained the insulin levels (Chaiyasit et al. 2009 ) .
The results suggested the potential clinical implications of C. frutescens in the management of type 2 diabetes.
Studies in streptozotocin induced type 2 diabetic male Sprague Dawley rats showed that after 4 weeks of feeding red chilli ( C. frutescens ) low (RCL, 0.5%) and red chilli high (RCH, 2.0%) the fasting blood glucose concentrations in both RC fed groups were not significantly different (Islam and Choi 2008 ) .
The serum insulin concentration was significantly increased in the RCH group compared with the diabetic control and RCL groups. Blood HbA1c, liver weight, liver glycogen and serum lipids were not in fluenced by the feeding of RC-containing diets.
The data suggested that 2% dietary RC was insulinotropic rather than hypoglycemic at least in the experimental condition. Rau et al. ( 2006 ) reported that several herbal extracts including C. frutescens were found to be most active in a concentration dependent manner in the activation of peroxisome proliferatoractivated receptors (PPAR) that play a pivotal role in lipid and glucose homeostasis.
Synthetic activators of PPARalpha ( fibrates) and PPARgamma (glitazones) are widely used for treatment of dislipidemia and diabetes, respectively.
immunological and anticancer activities
Studies had reported phenolic substances derived from spices such as curcumin, a yellow colouring agent, contained in turmeric ( Curcuma longa ), [6]-gingerol, a pungent ingredient present in ginger ( Zingiber of fi cinale ) and capsaicin, a principal pungent principle of hot chili pepper ( Capsicum annuum ) to possess potent antimutagenic and anticarcinogenic activities (Surh 2002 ) .
The chemopreventive effects exerted by these phytochemicals are often associated with their antioxidative and antiinflammatory activities mediated by intracellular signaling cascades, particularly those involving NF-kappaB and mitogen-activated protein kinases.
Lee et al. ( 2004 ) found that capsaicin induced apoptotic MBT-2 murine bladder tumour cell death in a time- and dose-dependent manner. In addition to the caspase-3 activation, capsaicin also induced cytochrome C release and decrease in Bcl-2 protein expression with no changes in the level of Bax.
Further, capsaicin at the concentration of inducing apoptosis also markedly reduced the level of reactive oxygen species and lipid peroxidation, implying that capsaicin may enhance the antitumour effect of bacillus Calmette-Guerin (BCG), the most effective intravesical bladder cancer treatment.
Mori et al. ( 2006 ) reported capsaicin to have a profound antiproliferative effect on prostate cancer cells, inducing the apoptosis of both androgen receptor (AR)-positive (LNCaP) and androgen receptor-negative (PC-3, DU-145) prostate cancer cell lines associated with an increase of p53, p21, and Bax. Capsaicin down-regulated the expression of not only prostate-specific antigen (PSA) but also AR. Capsaicin, when given orally, signi fi cantly slowed the growth of PC-3 prostate cancer xenografts as measured by size and weight compared to vehicle treated mice.
Malagarie-Cazenave et al. ( 2011 ) reported that capsaicin increased production of cytokine interleukin (IL)-6 in prostate PC-3 cancer cells mediated partly by tumour necrosis factor (TNF)- a secretion and signalling pathway involving Akt, ERK and PKC- a activation. Huang et al. ( 2009 ) found that capsaicin induced apoptosis in human hepatoma HepG2 cells.
The results indicated that the capsaicininduced apoptosis in HepG2 cells may result from the elevation of intracellular Ca2+ production, ROS, disruption of alpha psi(m), regulation of Bcl-2 family protein expression and caspase-3 activity.
Capsaicin exhibited anti-proliferative activity against four human small cell lung cancer SCLC cell lines in-vitro and potently suppressed the growth of H69 human SCLC tumours in-vivo as ascertained by chick chorioallantoic membrane (CAM) assays and nude mice models (Brown et al. 2010 ) .
The antiproliferative activity of capsaicin was mediated through the transcription factor E2F4 pathway. In another study, treatment with capsaicin (10 mg/kg body weight) to the lung carcinoma mice restored back the activities of phase I biotransformation enzymes (NADPHcytochrome P450 reductase, NADH-cytochrome b5 reductase and epoxide hydrolase), phase II enzymes (glutathione-S-transferase, UDPglucuronyl transferase and DT-diaphorase), and the levels of tumour markers to near normalcy (Anandakumar et al. 2009 ) .
The study revealed that capsaicin could effectively detoxify the carcinogens during benzo(a)pyrene-induced lung cancer. Wu et al. ( 2006 ) showed that capsaicin induced GO-G1 cell cycle arrest and apoptosis in a timedependent manner in human esophagus epidermoid carcinoma CE 81 T/VGH cells through activation of caspase-3 and intracellular Ca(2+) release pathway, and may have potential for the treatment of esophagus epidermoid carcinoma cells. Ip et al. ( 2012 ) found that capsaicin-induced cytotoxic effects (cell death) through G0/G1 phase arrest and induction of apoptosis of human nasopharyngeal carcinoma NPC-TW 039 cells in a dose-dependent fashion.
Capsaicin treatment induced endoplasmic reticulum (ER) stress by promoting the production of reactive oxygen species (ROS), increasing levels of inositol-requiring 1 enzyme (IRE1), growth arrest and DNAdamage-inducible 153 (GADD153) and glucose-regulated protein 78 (GRP78). Capsaicin elicited an increase in cytosolic Ca(2+), loss of the mitochondrial transmembrane potential ( DY ( m)), releases of cytochrome c and apoptosis-inducing factor (AIF), and activation of caspase-9 and -3.
These results suggested that ER stress- and mitochondria-mediated cell death is involved in capsaicin-induced apoptosis in NPC-TW 039 cells.
Studies showed that capsaicin induced cytotoxic effects cells in a time- and dose-dependent manner and increased reactive oxygen species (ROS) and Ca(2+) but decreased the level of mitochondrial membrane potential ( DY (m)) in human colon cancer colo 205 cells (Lu et al. 2010 ) .
Levels of Fas, cytochrome c, and caspases were increased, leading to cell apoptosis. Capsaicin decreased the levels of anti-apoptotic proteins such as Bcl-2 and increased the levels of pro-apoptotic proteins such as Bax. Capsaicininduced apoptosis in colo 205 cells was also done through the activations of caspase-8, -9 and -3. In-vivo studies in immunode fi cient nu/nu mice bearing colo 205 tumour xenografts showed that capsaicin effectively inhibited tumour growth.
Huh et al. ( 2011 ) reported that the combined treatment of capsaicin and cisplatin elicited higher apoptotic cell death of cisplatin-resistant Korean human gastric cancer cell line SNU-668 than that of treatment with either capsaicin or cisplatin alone.
The combined treatment induced G1/S arrest and inhibited I k B phosphorylation in a dose-dependent manner. Capsaicin potently inhibited growth of ER-positive (MCF-7, T47D, BT-474) and ER-negative (SKBR-3, MDA-MB231) breast cancer cell lines, which was associated with G(0)/G(1) cell-cycle arrest, increased levels of apoptosis and reduced protein expression of human epidermal growth factor receptor (EGFR), HER-2, activated extracellular-regulated kinase (ERK) and cyclin D1 (Thoennissen et al. 2010 ) .
Capsaicin blocked breast cancer cell migration in-vitro and decreased by 50% the size of MDA-MB231 breast cancer tumours growing orthotopically in immunode fi cient mice without noticeable drug side effects. In-vivo activation of ERK was clearly decreased, as well as expression of HER-2 and cyclin D1, whereas caspase activity and PARP cleavage products were increased in tumours of capsaicin-treated mice.
Besides, capsaicin potently inhibited the development of pre-neoplastic breast lesions by up to 80% without evidence of toxicity. Their data indicated capsaicin to be a novel modulator of the EGFR/HER-2 pathway in both ER-positive and -negative breast cancer cells with a potential role in the treatment and prevention of human breast cancer.
Kim et al. ( 2010 ) demonstrated that subtoxic doses of capsaicin effectively sensitized multiple malignant glioma (brain and spinal chord tumour) cell lines to tumour necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis.
Treatment of various gliomas with capsaicin signi fi cantly stimulated DR5, a death receptor of TRAIL, and suppressed the caspase inhibitor survivin. The results indicated that the activity of capsaicin toward DR5 and survivin contributed to the ampli fi cation of caspase cascades, thereby restoring TRAIL sensitivity in malignant glioma cells. Capsaicin and resveratrol, alone or in combination, inhibited cell growth and promoted apoptosis by the elevation of NO• in A375 human melanoma cells (Kim 2012 ) .
The data suggested that capsaicin and resveratrol activated the mitochondrial and death receptor pathways, working together to induce apoptosis in A375 cells, and indicated that NO• could be considered a potential target for improvement of the effectiveness of melanoma treatment.
Basu and Srivastava ( 2005 ) demonstrated that dendritic cells, a key cell type in vertebrate immune responses, possessed vanilloid receptor 1 (VR1), receptor for capsaicin, (8-methyl-N-vanillyl-6-nonenamide) the principal pungent ingredient of red chili pepper ( Capsicum frutescens ). Engagement of this receptor with capsaicin elicits powerful immune consequences.
Capsaicin had been reported to cause neurogenic in fl ammation and to have analgesic and antiinflammatory activities.
Beltran et al. ( 2007 ) further demonstrated that intratumoral administration of capsaicin into a preexisting tumour resulted in retarded progression of the injected tumour regardless of the stage of the tumour.
Further, capsaicin significantly inhibited growth of other, uninjected tumours in the same animal. Capsaicin-elicited immunity was shown to be T cell-mediated and tumour-specific. The results reflected the immunological potency of a neurological ligand in modulating immune response against an established tumour.
The chemopreventive effects exerted by these phytochemicals are often associated with their antioxidative and antiinflammatory activities mediated by intracellular signaling cascades, particularly those involving NF-kappaB and mitogen-activated protein kinases.
Lee et al. ( 2004 ) found that capsaicin induced apoptotic MBT-2 murine bladder tumour cell death in a time- and dose-dependent manner. In addition to the caspase-3 activation, capsaicin also induced cytochrome C release and decrease in Bcl-2 protein expression with no changes in the level of Bax.
Further, capsaicin at the concentration of inducing apoptosis also markedly reduced the level of reactive oxygen species and lipid peroxidation, implying that capsaicin may enhance the antitumour effect of bacillus Calmette-Guerin (BCG), the most effective intravesical bladder cancer treatment.
Mori et al. ( 2006 ) reported capsaicin to have a profound antiproliferative effect on prostate cancer cells, inducing the apoptosis of both androgen receptor (AR)-positive (LNCaP) and androgen receptor-negative (PC-3, DU-145) prostate cancer cell lines associated with an increase of p53, p21, and Bax. Capsaicin down-regulated the expression of not only prostate-specific antigen (PSA) but also AR. Capsaicin, when given orally, signi fi cantly slowed the growth of PC-3 prostate cancer xenografts as measured by size and weight compared to vehicle treated mice.
Malagarie-Cazenave et al. ( 2011 ) reported that capsaicin increased production of cytokine interleukin (IL)-6 in prostate PC-3 cancer cells mediated partly by tumour necrosis factor (TNF)- a secretion and signalling pathway involving Akt, ERK and PKC- a activation. Huang et al. ( 2009 ) found that capsaicin induced apoptosis in human hepatoma HepG2 cells.
The results indicated that the capsaicininduced apoptosis in HepG2 cells may result from the elevation of intracellular Ca2+ production, ROS, disruption of alpha psi(m), regulation of Bcl-2 family protein expression and caspase-3 activity.
Capsaicin exhibited anti-proliferative activity against four human small cell lung cancer SCLC cell lines in-vitro and potently suppressed the growth of H69 human SCLC tumours in-vivo as ascertained by chick chorioallantoic membrane (CAM) assays and nude mice models (Brown et al. 2010 ) .
The antiproliferative activity of capsaicin was mediated through the transcription factor E2F4 pathway. In another study, treatment with capsaicin (10 mg/kg body weight) to the lung carcinoma mice restored back the activities of phase I biotransformation enzymes (NADPHcytochrome P450 reductase, NADH-cytochrome b5 reductase and epoxide hydrolase), phase II enzymes (glutathione-S-transferase, UDPglucuronyl transferase and DT-diaphorase), and the levels of tumour markers to near normalcy (Anandakumar et al. 2009 ) .
The study revealed that capsaicin could effectively detoxify the carcinogens during benzo(a)pyrene-induced lung cancer. Wu et al. ( 2006 ) showed that capsaicin induced GO-G1 cell cycle arrest and apoptosis in a timedependent manner in human esophagus epidermoid carcinoma CE 81 T/VGH cells through activation of caspase-3 and intracellular Ca(2+) release pathway, and may have potential for the treatment of esophagus epidermoid carcinoma cells. Ip et al. ( 2012 ) found that capsaicin-induced cytotoxic effects (cell death) through G0/G1 phase arrest and induction of apoptosis of human nasopharyngeal carcinoma NPC-TW 039 cells in a dose-dependent fashion.
Capsaicin treatment induced endoplasmic reticulum (ER) stress by promoting the production of reactive oxygen species (ROS), increasing levels of inositol-requiring 1 enzyme (IRE1), growth arrest and DNAdamage-inducible 153 (GADD153) and glucose-regulated protein 78 (GRP78). Capsaicin elicited an increase in cytosolic Ca(2+), loss of the mitochondrial transmembrane potential ( DY ( m)), releases of cytochrome c and apoptosis-inducing factor (AIF), and activation of caspase-9 and -3.
These results suggested that ER stress- and mitochondria-mediated cell death is involved in capsaicin-induced apoptosis in NPC-TW 039 cells.
Studies showed that capsaicin induced cytotoxic effects cells in a time- and dose-dependent manner and increased reactive oxygen species (ROS) and Ca(2+) but decreased the level of mitochondrial membrane potential ( DY (m)) in human colon cancer colo 205 cells (Lu et al. 2010 ) .
Levels of Fas, cytochrome c, and caspases were increased, leading to cell apoptosis. Capsaicin decreased the levels of anti-apoptotic proteins such as Bcl-2 and increased the levels of pro-apoptotic proteins such as Bax. Capsaicininduced apoptosis in colo 205 cells was also done through the activations of caspase-8, -9 and -3. In-vivo studies in immunode fi cient nu/nu mice bearing colo 205 tumour xenografts showed that capsaicin effectively inhibited tumour growth.
Huh et al. ( 2011 ) reported that the combined treatment of capsaicin and cisplatin elicited higher apoptotic cell death of cisplatin-resistant Korean human gastric cancer cell line SNU-668 than that of treatment with either capsaicin or cisplatin alone.
The combined treatment induced G1/S arrest and inhibited I k B phosphorylation in a dose-dependent manner. Capsaicin potently inhibited growth of ER-positive (MCF-7, T47D, BT-474) and ER-negative (SKBR-3, MDA-MB231) breast cancer cell lines, which was associated with G(0)/G(1) cell-cycle arrest, increased levels of apoptosis and reduced protein expression of human epidermal growth factor receptor (EGFR), HER-2, activated extracellular-regulated kinase (ERK) and cyclin D1 (Thoennissen et al. 2010 ) .
Capsaicin blocked breast cancer cell migration in-vitro and decreased by 50% the size of MDA-MB231 breast cancer tumours growing orthotopically in immunode fi cient mice without noticeable drug side effects. In-vivo activation of ERK was clearly decreased, as well as expression of HER-2 and cyclin D1, whereas caspase activity and PARP cleavage products were increased in tumours of capsaicin-treated mice.
Besides, capsaicin potently inhibited the development of pre-neoplastic breast lesions by up to 80% without evidence of toxicity. Their data indicated capsaicin to be a novel modulator of the EGFR/HER-2 pathway in both ER-positive and -negative breast cancer cells with a potential role in the treatment and prevention of human breast cancer.
Kim et al. ( 2010 ) demonstrated that subtoxic doses of capsaicin effectively sensitized multiple malignant glioma (brain and spinal chord tumour) cell lines to tumour necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis.
Treatment of various gliomas with capsaicin signi fi cantly stimulated DR5, a death receptor of TRAIL, and suppressed the caspase inhibitor survivin. The results indicated that the activity of capsaicin toward DR5 and survivin contributed to the ampli fi cation of caspase cascades, thereby restoring TRAIL sensitivity in malignant glioma cells. Capsaicin and resveratrol, alone or in combination, inhibited cell growth and promoted apoptosis by the elevation of NO• in A375 human melanoma cells (Kim 2012 ) .
The data suggested that capsaicin and resveratrol activated the mitochondrial and death receptor pathways, working together to induce apoptosis in A375 cells, and indicated that NO• could be considered a potential target for improvement of the effectiveness of melanoma treatment.
Basu and Srivastava ( 2005 ) demonstrated that dendritic cells, a key cell type in vertebrate immune responses, possessed vanilloid receptor 1 (VR1), receptor for capsaicin, (8-methyl-N-vanillyl-6-nonenamide) the principal pungent ingredient of red chili pepper ( Capsicum frutescens ). Engagement of this receptor with capsaicin elicits powerful immune consequences.
Capsaicin had been reported to cause neurogenic in fl ammation and to have analgesic and antiinflammatory activities.
Beltran et al. ( 2007 ) further demonstrated that intratumoral administration of capsaicin into a preexisting tumour resulted in retarded progression of the injected tumour regardless of the stage of the tumour.
Further, capsaicin significantly inhibited growth of other, uninjected tumours in the same animal. Capsaicin-elicited immunity was shown to be T cell-mediated and tumour-specific. The results reflected the immunological potency of a neurological ligand in modulating immune response against an established tumour.
Hypolipidemic/Antihypercholesterolemic
Activities
đInclusion of capsaicin (0.015%) in the cholesterolenriched diet of rats produced signi fi cant hypocholesterolemic effect (Kempaiah et al. 2005 ) .
Results suggested capsaicin was protective to low-density lipoprotein oxidation both in-vivo and in-vitro under normal situation, while in hypercholesterolemic situation where the extent of low-density lipoprotein oxidation was already lowered, capsaicin did not offer any further reduction.
Dietary curcumin (0.2%), capsaicin (0.015%) or their combination signi fi cantly countered the hypercholesterolemia brought about by high cholesterol feeding (Manjunatha and Srinivasan 2007b ) .
Hepatic cholesterol was lowered in normal rats by both but hepatic triglyceride levels were lowered in both normal and hypercholesterolemic rats by capsaicin.
Curcumin and capsaicin lowered hepatic and blood lipid peroxides in hypercholesterolemic rats, while the effect in blood was additive with their combination.
Hepatic ascorbic acid was enhanced by dietary spice principles in normal rats; glutathione was enhanced by their combination only in hypercholesterolemic rats.
Activities of serum glutathione reductase, glutathione transferase and catalase and hepatic glutathione reductase in normal rats and serum glutathione peroxidase in hypercholesterolemic rats were enhanced by both curcumin and capsaicin. While dietary curcumin and capsaicin normalized the changes in the levels of antioxidant molecules and activities of antioxidant enzymes to a significant extent, this effect was not generally additive when given in combination.
Dietary high-fat (30%)-induced hypertriglyceridemia in rats was countered by dietary curcumin, capsaicin, or their combination by 12–20% (Manjunatha and Srinivasan 2007a ) .
Curcumin, capsaicin, and their combination decreased serum total cholesterol and lipid peroxide levels in these animals.
Serum alphatocopherol, hepatic glutathione, glutathione peroxidase and glutathione transferase contents were increased by dietary curcumin, capsaicin, and their combination in high-fat-fed rats.
Hepatic glutathione reductase and glutathione peroxidase were significantly elevated by dietary spice principles in high-fat-fed animals.
The additive effect of the two bioactive compounds was generally not evident with respect to hypolipidemic or antioxidant potential.
However, the effectiveness of the combination was higher in a few instances.
The lithogenic diet that contained capsaicin, curcumin, or their combination reduced the incidence of cholesterol gallstones by 50, 66, and 56%, respectively, compared with lithogenic control mice (Shubha et al. 2011 ) .
This was accompanied by reduced biliary cholesterol and a marginal increase in phospholipid in these spice-fed rats.
Increased cholesterol saturation index and cholesterol: phospholipid ratio in the bile caused by the lithogenic diet was countered by the dietary spice compounds.
Combination of both species countered the decreased activities of hepatic glutathione reductase and glutathione-S-transferase caused by the lithogenic diet.
The increased lipid peroxidation and the decreased concentration of ascorbic acid in the liver caused by the lithogenic diet was also countered by the dietary spice compounds, individually or in combination.
Though the capsaicin and curcumin combination did not have an additive in fluence in reducing the incidence of cholesterol gallstones in mice, their combination nevertheless was more beneficial in enhancing the activity of hepatic antioxidant enzyme ─ glutathione reductase in the lithogenic situation.
Results suggested capsaicin was protective to low-density lipoprotein oxidation both in-vivo and in-vitro under normal situation, while in hypercholesterolemic situation where the extent of low-density lipoprotein oxidation was already lowered, capsaicin did not offer any further reduction.
Dietary curcumin (0.2%), capsaicin (0.015%) or their combination signi fi cantly countered the hypercholesterolemia brought about by high cholesterol feeding (Manjunatha and Srinivasan 2007b ) .
Hepatic cholesterol was lowered in normal rats by both but hepatic triglyceride levels were lowered in both normal and hypercholesterolemic rats by capsaicin.
Curcumin and capsaicin lowered hepatic and blood lipid peroxides in hypercholesterolemic rats, while the effect in blood was additive with their combination.
Hepatic ascorbic acid was enhanced by dietary spice principles in normal rats; glutathione was enhanced by their combination only in hypercholesterolemic rats.
Activities of serum glutathione reductase, glutathione transferase and catalase and hepatic glutathione reductase in normal rats and serum glutathione peroxidase in hypercholesterolemic rats were enhanced by both curcumin and capsaicin. While dietary curcumin and capsaicin normalized the changes in the levels of antioxidant molecules and activities of antioxidant enzymes to a significant extent, this effect was not generally additive when given in combination.
Dietary high-fat (30%)-induced hypertriglyceridemia in rats was countered by dietary curcumin, capsaicin, or their combination by 12–20% (Manjunatha and Srinivasan 2007a ) .
Curcumin, capsaicin, and their combination decreased serum total cholesterol and lipid peroxide levels in these animals.
Serum alphatocopherol, hepatic glutathione, glutathione peroxidase and glutathione transferase contents were increased by dietary curcumin, capsaicin, and their combination in high-fat-fed rats.
Hepatic glutathione reductase and glutathione peroxidase were significantly elevated by dietary spice principles in high-fat-fed animals.
The additive effect of the two bioactive compounds was generally not evident with respect to hypolipidemic or antioxidant potential.
However, the effectiveness of the combination was higher in a few instances.
The lithogenic diet that contained capsaicin, curcumin, or their combination reduced the incidence of cholesterol gallstones by 50, 66, and 56%, respectively, compared with lithogenic control mice (Shubha et al. 2011 ) .
This was accompanied by reduced biliary cholesterol and a marginal increase in phospholipid in these spice-fed rats.
Increased cholesterol saturation index and cholesterol: phospholipid ratio in the bile caused by the lithogenic diet was countered by the dietary spice compounds.
Combination of both species countered the decreased activities of hepatic glutathione reductase and glutathione-S-transferase caused by the lithogenic diet.
The increased lipid peroxidation and the decreased concentration of ascorbic acid in the liver caused by the lithogenic diet was also countered by the dietary spice compounds, individually or in combination.
Though the capsaicin and curcumin combination did not have an additive in fluence in reducing the incidence of cholesterol gallstones in mice, their combination nevertheless was more beneficial in enhancing the activity of hepatic antioxidant enzyme ─ glutathione reductase in the lithogenic situation.
antiinflamatory activity
On acute treatment, capsaicin (extracted from Capsicum frutescens and standard capsaicin from Sigma Chemicals) produced a dose-related in fl ammatory response in rat paw as measured by the volume displacement method (De and Ghosh 1988 ) .
This response was found to be synergestic when injected with carrageenan. In contrast, chronically capsaicin treated rats (for 10 days) showed a significant inhibition of paw oedema when treated with either carregeenan or a single high dose of capsaicin.
Both the extracted and the standard capsaicin showed a similar type of response in all experiments. A comparison of the extent of carrageenaninduced paw in fl ammation showed that both dietary curcumin and capsaicin moderately lowered in fl ammation, while the their combination were more effective (Manjunatha and Srinivasan 2006 ) .
Dietary curcumin and capsaicin significantly decreased the activity of 5 ¢ - lipoxygenase activity in the polymorphonuclear lymphocytes in carrageenan-injected rats, the decrease being even higher in the case of combination of these two spice principles.
Kim et al. ( 2003 ) found that capsaicin exhibited antiinflammatory activity by inhibiting IkB-a degradation in lipopolysaccharide-stimulated murine peritoneal macrophages.
Significant inhibition of the production of LPS-induced PGE2 by capsaicin was observed in a dose-dependent manner.
Capsaicin inhibited the enzyme activity of COX-2 and the expression of the iNOS protein.
Capsaicin completely blocked LPS-induced disappearance of IkB-a and therefore inactivated NF-kB. A high expression level of the VR-1 like protein (VRL-1) was observed in peritoneal macrophages, while the expression of VR-1 was not detected.
These findings suggested that the antiinflammatory action of capsaicin may occur through a novel mechanism, not by a VR-1 receptor-mediated one.
In the endotoxin lipopolysaccharide-treated rats, hepatic reduced glutathione (GSH) and malondialdehyde MDA increased signi fi cantly after capsaicin administration (Abdel-Salam et al. 2012 ) .
In lung tissue, both MDA and GSH were decreased by capsaicin administration but in the brain GSH increased significantly. Increase in serum ALT and ALP and nitric oxide after lipopolysaccharide treatment was decreased by capsaicin serum glucose increased markedly after the administration of lipopolysaccharide, and was normalized by capsaicin treatment.
The findings suggested that in the presence of mild systemic in flammation, acute capsaicin administration might alter oxidative status in some tissues and exert an antiin flammatory effect.
Capsaicin exerted protective effects in the liver and lung against the lipopolysaccharide -induced tissue damage.
Choi et al. ( 2011 ) found that capsaicin attenuated palmitate-induced expression of macrophage inflammatory protein 1 and interleukin 8 by increasing palmitate oxidation and reducing c-Jun activation in THP-1 (human acute monocytic leukemia) cells.
This response was found to be synergestic when injected with carrageenan. In contrast, chronically capsaicin treated rats (for 10 days) showed a significant inhibition of paw oedema when treated with either carregeenan or a single high dose of capsaicin.
Both the extracted and the standard capsaicin showed a similar type of response in all experiments. A comparison of the extent of carrageenaninduced paw in fl ammation showed that both dietary curcumin and capsaicin moderately lowered in fl ammation, while the their combination were more effective (Manjunatha and Srinivasan 2006 ) .
Dietary curcumin and capsaicin significantly decreased the activity of 5 ¢ - lipoxygenase activity in the polymorphonuclear lymphocytes in carrageenan-injected rats, the decrease being even higher in the case of combination of these two spice principles.
Kim et al. ( 2003 ) found that capsaicin exhibited antiinflammatory activity by inhibiting IkB-a degradation in lipopolysaccharide-stimulated murine peritoneal macrophages.
Significant inhibition of the production of LPS-induced PGE2 by capsaicin was observed in a dose-dependent manner.
Capsaicin inhibited the enzyme activity of COX-2 and the expression of the iNOS protein.
Capsaicin completely blocked LPS-induced disappearance of IkB-a and therefore inactivated NF-kB. A high expression level of the VR-1 like protein (VRL-1) was observed in peritoneal macrophages, while the expression of VR-1 was not detected.
These findings suggested that the antiinflammatory action of capsaicin may occur through a novel mechanism, not by a VR-1 receptor-mediated one.
In the endotoxin lipopolysaccharide-treated rats, hepatic reduced glutathione (GSH) and malondialdehyde MDA increased signi fi cantly after capsaicin administration (Abdel-Salam et al. 2012 ) .
In lung tissue, both MDA and GSH were decreased by capsaicin administration but in the brain GSH increased significantly. Increase in serum ALT and ALP and nitric oxide after lipopolysaccharide treatment was decreased by capsaicin serum glucose increased markedly after the administration of lipopolysaccharide, and was normalized by capsaicin treatment.
The findings suggested that in the presence of mild systemic in flammation, acute capsaicin administration might alter oxidative status in some tissues and exert an antiin flammatory effect.
Capsaicin exerted protective effects in the liver and lung against the lipopolysaccharide -induced tissue damage.
Choi et al. ( 2011 ) found that capsaicin attenuated palmitate-induced expression of macrophage inflammatory protein 1 and interleukin 8 by increasing palmitate oxidation and reducing c-Jun activation in THP-1 (human acute monocytic leukemia) cells.
capsiacin and dyspepsia
Functional dyspepsia (FD) is a common and distressing chronic, recurrent, digestive disorder in the upper gastrointestinal tract of unknown cause (Nyren et al. 1992 ) .
Functional dyspepsia impacts negatively on work productivity by lowering productivity and increasing production cost through absenteeism, lower work out put and higher medical treatment cost (Brook et al. 2010 ) .
Studies by Rodriguez-Stanley et al. ( 2000 ) found that consumption of meal plus 5 mg capsaicin gelatine capsule enhanced noxious postprandial heartburn, presumably by direct effects on sensory neurons.
Capsaicin did not alter dyspepsia score, oesophageal and gastric pH pro fi les and gastric emptying. In a randomised double blind study of 15 patients with FD, administration of red pepper powder containing 0.7 mg capsaicin, for 5 weeks was found more effective than placebo in decreasing the intensity of dyspeptic symptoms namely epigastric pain, epigastric fullness, and nausea, probably through a capsaicininduced desensitization of gastric nociceptive C fi bers (Bortolotti et al. 2002 ) .
The capsaicin test requiring patients to swallow a capsule containing 0.75 mg capsaicin was found to be a simple and non-invasive method to detect a subgroup of functional dyspepsia with chemical hypersensitivity (Hammer et al. 2008 ) .
Führer and Hammer ( 2009 ) found that 4 weeks ingestion of capsaicin desensitized both chemonociceptive and mechanonociceptive pathways in healthy volunteers.
Symptom reduction after prolonged treatment with capsaicin in dyspeptic patients might be attributed to a dual desensitizing effect of capsaicin on chemonociceptors and mechanonociceptors.
In a doubleblind, placebo-controlled trial of involving a total of 116 outpatients with upper gastrointestinal (GI) symptoms, 73 patients were diagnosed with functional dyspepsia after swallowing a capsule containing 0.75 mg (Führer et al. 2011 ) .
Half of functional dyspepsia patients had chemical hypersensitivity, determined with an oral capsaicin load.
Placebo response was negligible.
The results suggested that visceral hypersensitivity may play a key role in the pathophysiology of functional dyspepsia.
Functional dyspepsia impacts negatively on work productivity by lowering productivity and increasing production cost through absenteeism, lower work out put and higher medical treatment cost (Brook et al. 2010 ) .
Studies by Rodriguez-Stanley et al. ( 2000 ) found that consumption of meal plus 5 mg capsaicin gelatine capsule enhanced noxious postprandial heartburn, presumably by direct effects on sensory neurons.
Capsaicin did not alter dyspepsia score, oesophageal and gastric pH pro fi les and gastric emptying. In a randomised double blind study of 15 patients with FD, administration of red pepper powder containing 0.7 mg capsaicin, for 5 weeks was found more effective than placebo in decreasing the intensity of dyspeptic symptoms namely epigastric pain, epigastric fullness, and nausea, probably through a capsaicininduced desensitization of gastric nociceptive C fi bers (Bortolotti et al. 2002 ) .
The capsaicin test requiring patients to swallow a capsule containing 0.75 mg capsaicin was found to be a simple and non-invasive method to detect a subgroup of functional dyspepsia with chemical hypersensitivity (Hammer et al. 2008 ) .
Führer and Hammer ( 2009 ) found that 4 weeks ingestion of capsaicin desensitized both chemonociceptive and mechanonociceptive pathways in healthy volunteers.
Symptom reduction after prolonged treatment with capsaicin in dyspeptic patients might be attributed to a dual desensitizing effect of capsaicin on chemonociceptors and mechanonociceptors.
In a doubleblind, placebo-controlled trial of involving a total of 116 outpatients with upper gastrointestinal (GI) symptoms, 73 patients were diagnosed with functional dyspepsia after swallowing a capsule containing 0.75 mg (Führer et al. 2011 ) .
Half of functional dyspepsia patients had chemical hypersensitivity, determined with an oral capsaicin load.
Placebo response was negligible.
The results suggested that visceral hypersensitivity may play a key role in the pathophysiology of functional dyspepsia.
Capsaicin and Neuralgia, Post-Herpetic
Neuralgia, Diabetic Peripheral
Neuropathy, Rheumatoid Arthritis,
Osteoarthritis
Exposure to significantly high levels of capsaicin ( trans -8-methyl-N-vanillyl-6-nonenamide), a component of hot red-peppers ( Capsicum annum , C. frustescens , C. chinense ) powder, and had been reported to permanently impair the nociceptive C fibers carrying pain sensations to the central nervous system in rats and had been shown to relieve pain of cutaneous and mucosal origin and gave promising results in post-herpetic neuralgia (Lynn 1990 ) .
Capsaicin as a pure white crystalline material, acts specifically by depleting stores of substance P from sensory neurons, and has been successful in the treatment of several painful conditions (e.g., rheumatoid arthritis, osteoarthritis, peripheral neuropathies) (Cordell and Araujo 1993 ) .
However, the crude, dark oleoresin extract of Capsicum contains over 100 distinct volatile compounds and therefore may function in many ways dissimilar to capsaicin, the oleoresin continues to be marketed in products with a high degree of variability in efficacy.
Of the 12 patients with post herpetic neuralgia, who applied capsaicin to painful areas of skin for 4 weeks, 9 (75%) experienced substantial relief of their pain in a preliminary study (Bernstein et al. 1987 ) .
The only adverse reaction was an intermittent, localized burning sensation experienced by one patient with application of capsaicin.
Capsaicin was reported to deplete substance P, an important chemomediator of nociceptive impulses from the periphery to the central nervous system and had been demonstrated in high levels in sensory nerves supplying sites of chronic inflammation.
Postherpetic neuralgia occurred after herpes zoster in about one third of patients ³ 60 years old and could persist for months or even years.
In a study on the consequences of long-term topical capsaicin application on the hind paws of rats, McMahon et al. ( 1991 ) found that after 10 weeks of capsaicin application, the ability of C fibres to produce neurogenic extravasation was markedly reduced.
After 4 weeks of recovery this ability returned to normal in 0.075% capsaicin-treated animals, but remained impaired in the 0.75% group which exhibited partial recovery 12 weeks after the end of treatment.
The levels of substance P and calcitonin-gene-related peptide in the sural nerve supplying the treated skin area were unchanged after both the 0.075 and 0.75% capsaicin treatments.
The results suggested that the topical application of capsaicin at low concentration produced a reversible impairment of the terminals of C fi bres in the skin without greatly exciting those fi bres and without affecting the properties of cell soma. Topical capsaicin treatment did not produce any cell death in the adult animal.
In another double-blind study of 32 elderly patients with chronic postherpetic neuralgia, after 6 weeks almost 80% of capsaicin-treated patients experienced some relief from their pain compared with vehicle (Bernstein et al. 1989 ) .
Results of un-controlled studies by Frucht-Pery et al. ( 1997 ) suggested that capsaicin may be a useful therapy for the alleviation of neuralgia in some individuals with herpes zoster ophthalmicus.
Significantly greater relief in the capsaicin-treated group compared with vehicle was observed for all efficacy variables.
In a double-blind randomized study, 70 patients with osteoarthritis (OA) and 31 with rheumatoid arthritis (RA), signi fi cantly more relief of pain was reported by the capsaicintreated patients than the placebo patients throughout the study; after 4 weeks of capsaicin treatment, RA and OA patients demonstrated mean reductions in pain of 57 and 33%, respectively (Deal et al. 1991 ) .
These reductions in pain were statistically significant compared with those reported with placebo. They concluded capsaicin cream to be a safe and effective treatment for arthritis.
The findings of a 4 week double blind, placebo controlled randomized trial of 21 patients comprising 7 with rheumatoid arthritis and 14 with osteoarthritis suggested topical capsaicin to be a safe and potentially useful drug for the treatment of painful osteoarthritis of the hands (McCarthy and McCarthy 1992 ) .
Capsaicin reduced tenderness and pain associated with osteoarthritis but not rheumatoid arthritis as compared with placebo.
In a cross-over, double blinded, randomized, controlled trial of 100 patients averaged 61 years age with mild to moderate knee osteoarthritis, 0.0125% capsaicin gel was found to an effective treatment (Kosuwon et al. 2010 ) .
The burning sensation reported by patients in the capsaicin group was less disturbing than in previous studies and none of the present patients withdrew for this reason.
In a double-blind, randomised parallel-group involving 154 patients with non-speci fi c back pain, the use of capsicum plaster for 3 weeks elicited marked improvement over placebo (Keitel et al. 2001 ) .
The sum of the three separate pain scales decreased more markedly in the capsicum group than in the placebo group (38.5% compared to 28.0%;).
Relatively slight improvements of the impaired mobility and the functional status were explained by the characteristics of the d isorder treated.
The efficacy ratings by observers and patients was definitely in favour of capsicum. Their results confirmed the findings of other double-blind clinical studies that showed local capsicum preparations to be very suitable for the treatment of neuropathic pain, musculoskeletal disorders, osteoarthritis, or fibromyalgia with or without in flammatory components.
Topically applied capsaicin induces the release of substance P, a neurotransmitter, from sensory C- fi bres.
In another double-blind, randomised, placebocontrolled multicentre parallel group study of 320 patients comprising 160 subjects treated by capsicum plaster and 160 subjects treated by placebo plaster, they con fi rmed the statistically significant superiority of the capsicum plaster treatment for chronic non-specific low back pain compared to placebo (Frerick et al. 2003 ) .
Park et al. ( 2004 ) found that capsicum plaster applied at the K-A20 acupuncture point on hands was effective in preventing postoperative sore throat in 150 patients scheduled to undergo abdominal hysterectomy.
The prevalence of moderate to severe sore throat at 24 h was lower for the plaster group (0%) than for sham (16%) and placebo controls (19%).
Gagnier et al. ( 2007 ) in their systemic review of randomised trials on the effects of herbal medicine for chronic low back pain, found three low-quality trials using Capsicum frutescens (Cayenne) in various topical preparations provided moderate evidence for favorable results against placebo and one trial found equivalence to a homeopathic ointment.
In a multicentre, double-blind, parallel-group trial, of 402 patients aged 18–90 years, who had postherpetic neuralgia for at least 6 months, patients who were randomly assigned to NGX4010 (n = 206) had a signi fi cantly greater reduction in pain during weeks two to eight than did patients who had the control patch (n = 196) (Backonja et al. 2008 ) .
The patients who had NGX-4010 had signi fi cant improvements in pain during weeks 2 to 12 (mean change in numeric pain rating scale (NPRS) score –29.9%vs –20.4%, difference –9.5, –15.39 to –3.61).
Transient blood pressure changes associated with changes in pain level were recorded on the day of treatment, and short-lasting erythema and pain at the site of application were common, self-limited, and generally mild to moderate in the NGX-4010 group and less frequent and severe in the controls.
The study showed that one 60-min application of NGX-4010 provided rapid and sustained pain relief in patients with postherpetic neuralgia.
No adverse events were associated with treatment except for local reactions at the site of application and those related to treatment-associated pain.
Further studies by Backonja et al. ( 2010 ) found NGX-4010 (high concentration capsain patch) to be a promising topical treatment for postherpetic neuralgia patients and to be tolerable, generally safe, and effective.
During days 8–28 after the double-blind treatment, NGX-4010 patients had a mean change in numerical pain rating scale (NPRS) scores from baseline of –32.7% compared with –4.4% for control patients.
A similar decrease in NPRS scores from baseline was maintained with subsequent NGX-4010 treatments, regardless of the number of treatments received. Transient increases in application site pain were adequately managed with analgesics.
No increases in application site reactions or adverse events were observed with repeated treatments.
An open label study of 106 patients with moderate to severe postherpetic neuralgia (PHN) and painful human immunode fi ciency virus-associated distal sensory polyneuropathy (HIV-DSP) showed that that repeated treatments with NGX-4010, a high-concentration capsaicin patch (capsaicin 8%), was found to be generally safe and well tolerated (Simpson et al. 2010 ) .
The most frequently reported treatment-emergent adverse events were transient, mild-to-moderate application site erythema, pain, edema, and papules.
Small, transient pain-related increases in blood pressure during and immediately after NGX-4010 application were observed.
There was no evidence of an increased incidence of adverse events, dermal irritation, intolerability, or impaired neurological function with repeated treatments.
Peppin et al. ( 2011 ) found that transient patch application-related pain with NGX4010 (a capsaicin 8% dermal patch) could be managed with local cooling and/or oral analgesics in nearly all cases.
Patient adherence to the full intended treatment duration indicated that patch application-related pain was not a barrier to NGX-4010 use. In pivotal, randomized, double-blind, multicentre trials in adults with non-diabetic peripheral neuropathic pain, a single 60-min application of capsaicin dermal patch (8% capsaicin) reduced the mean numeric pain rating scale (NPRS) scores from baseline to a signi fi cantly greater extent than a low-concentration (0.04% w/w capsaicin) control patch during weeks 2–8 (McCormack 2010 ) .
In randomized, doubleblind, multicentre trials in patients with HIVassociated neuropathy, capsaicin dermal patch reduced the mean NPRS scores from baseline significantly more than control in one study for the 30- and 90-min, but not the 60-min, application during weeks 2–12. In another study, the differences between capsaicin (30- and 60-min applications) and control did not reach statistical signi fi cance.
An integrated analysis of both studies showed that the 30-min application of capsaicin dermal patch was significantly better than control for the reduction from baseline in mean NPRS scores during weeks 2–12.
The efficacy of capsaicin dermal patch was maintained for up to 1 year in extension studies in which patients could receive up to three or four repeat treatments.
Capsaicin dermal patch was generally well tolerated in clinical trials. The most common adverse events were transient, mostly mild to moderate, application-site reactions.
Capsaicin had also been reported to have proven ef fi cacy as a topical treatment for painful diabetic peripheral neuropathy (Tesfaye et al. 2011 ) .
Capsaicin is not generally recognized as safe and effective by the U.S. Food and Drug Administration for fever blister and cold sore treatment, but is considered to be safe and effective as an external analgesic counterirritant (Anonymous 2007 ) .
A patch containing 8% capsaicin (research code NGX-4010 and marketed under the trade name Qutenza( ® )), approved both in the EU and USA, provides a localized therapy with effects for neuralgia lasting up to 12 weeks after a single 60-min application based clinical trial evidence on the safety, ef fi cacy and unique attributes of this capsaicin 8% patch. (Wallace and Pappagallo 2011 ) .
The FDA has approved a topical 8% patch formulation of capsaicin (Qutenza-NeurogesX), available only by prescription, for local treatment of postherpetic neuralgia (Anonymous 2011 ) .
Capsaicin as a pure white crystalline material, acts specifically by depleting stores of substance P from sensory neurons, and has been successful in the treatment of several painful conditions (e.g., rheumatoid arthritis, osteoarthritis, peripheral neuropathies) (Cordell and Araujo 1993 ) .
However, the crude, dark oleoresin extract of Capsicum contains over 100 distinct volatile compounds and therefore may function in many ways dissimilar to capsaicin, the oleoresin continues to be marketed in products with a high degree of variability in efficacy.
Of the 12 patients with post herpetic neuralgia, who applied capsaicin to painful areas of skin for 4 weeks, 9 (75%) experienced substantial relief of their pain in a preliminary study (Bernstein et al. 1987 ) .
The only adverse reaction was an intermittent, localized burning sensation experienced by one patient with application of capsaicin.
Capsaicin was reported to deplete substance P, an important chemomediator of nociceptive impulses from the periphery to the central nervous system and had been demonstrated in high levels in sensory nerves supplying sites of chronic inflammation.
Postherpetic neuralgia occurred after herpes zoster in about one third of patients ³ 60 years old and could persist for months or even years.
In a study on the consequences of long-term topical capsaicin application on the hind paws of rats, McMahon et al. ( 1991 ) found that after 10 weeks of capsaicin application, the ability of C fibres to produce neurogenic extravasation was markedly reduced.
After 4 weeks of recovery this ability returned to normal in 0.075% capsaicin-treated animals, but remained impaired in the 0.75% group which exhibited partial recovery 12 weeks after the end of treatment.
The levels of substance P and calcitonin-gene-related peptide in the sural nerve supplying the treated skin area were unchanged after both the 0.075 and 0.75% capsaicin treatments.
The results suggested that the topical application of capsaicin at low concentration produced a reversible impairment of the terminals of C fi bres in the skin without greatly exciting those fi bres and without affecting the properties of cell soma. Topical capsaicin treatment did not produce any cell death in the adult animal.
In another double-blind study of 32 elderly patients with chronic postherpetic neuralgia, after 6 weeks almost 80% of capsaicin-treated patients experienced some relief from their pain compared with vehicle (Bernstein et al. 1989 ) .
Results of un-controlled studies by Frucht-Pery et al. ( 1997 ) suggested that capsaicin may be a useful therapy for the alleviation of neuralgia in some individuals with herpes zoster ophthalmicus.
Significantly greater relief in the capsaicin-treated group compared with vehicle was observed for all efficacy variables.
In a double-blind randomized study, 70 patients with osteoarthritis (OA) and 31 with rheumatoid arthritis (RA), signi fi cantly more relief of pain was reported by the capsaicintreated patients than the placebo patients throughout the study; after 4 weeks of capsaicin treatment, RA and OA patients demonstrated mean reductions in pain of 57 and 33%, respectively (Deal et al. 1991 ) .
These reductions in pain were statistically significant compared with those reported with placebo. They concluded capsaicin cream to be a safe and effective treatment for arthritis.
The findings of a 4 week double blind, placebo controlled randomized trial of 21 patients comprising 7 with rheumatoid arthritis and 14 with osteoarthritis suggested topical capsaicin to be a safe and potentially useful drug for the treatment of painful osteoarthritis of the hands (McCarthy and McCarthy 1992 ) .
Capsaicin reduced tenderness and pain associated with osteoarthritis but not rheumatoid arthritis as compared with placebo.
In a cross-over, double blinded, randomized, controlled trial of 100 patients averaged 61 years age with mild to moderate knee osteoarthritis, 0.0125% capsaicin gel was found to an effective treatment (Kosuwon et al. 2010 ) .
The burning sensation reported by patients in the capsaicin group was less disturbing than in previous studies and none of the present patients withdrew for this reason.
In a double-blind, randomised parallel-group involving 154 patients with non-speci fi c back pain, the use of capsicum plaster for 3 weeks elicited marked improvement over placebo (Keitel et al. 2001 ) .
The sum of the three separate pain scales decreased more markedly in the capsicum group than in the placebo group (38.5% compared to 28.0%;).
Relatively slight improvements of the impaired mobility and the functional status were explained by the characteristics of the d isorder treated.
The efficacy ratings by observers and patients was definitely in favour of capsicum. Their results confirmed the findings of other double-blind clinical studies that showed local capsicum preparations to be very suitable for the treatment of neuropathic pain, musculoskeletal disorders, osteoarthritis, or fibromyalgia with or without in flammatory components.
Topically applied capsaicin induces the release of substance P, a neurotransmitter, from sensory C- fi bres.
In another double-blind, randomised, placebocontrolled multicentre parallel group study of 320 patients comprising 160 subjects treated by capsicum plaster and 160 subjects treated by placebo plaster, they con fi rmed the statistically significant superiority of the capsicum plaster treatment for chronic non-specific low back pain compared to placebo (Frerick et al. 2003 ) .
Park et al. ( 2004 ) found that capsicum plaster applied at the K-A20 acupuncture point on hands was effective in preventing postoperative sore throat in 150 patients scheduled to undergo abdominal hysterectomy.
The prevalence of moderate to severe sore throat at 24 h was lower for the plaster group (0%) than for sham (16%) and placebo controls (19%).
Gagnier et al. ( 2007 ) in their systemic review of randomised trials on the effects of herbal medicine for chronic low back pain, found three low-quality trials using Capsicum frutescens (Cayenne) in various topical preparations provided moderate evidence for favorable results against placebo and one trial found equivalence to a homeopathic ointment.
In a multicentre, double-blind, parallel-group trial, of 402 patients aged 18–90 years, who had postherpetic neuralgia for at least 6 months, patients who were randomly assigned to NGX4010 (n = 206) had a signi fi cantly greater reduction in pain during weeks two to eight than did patients who had the control patch (n = 196) (Backonja et al. 2008 ) .
The patients who had NGX-4010 had signi fi cant improvements in pain during weeks 2 to 12 (mean change in numeric pain rating scale (NPRS) score –29.9%vs –20.4%, difference –9.5, –15.39 to –3.61).
Transient blood pressure changes associated with changes in pain level were recorded on the day of treatment, and short-lasting erythema and pain at the site of application were common, self-limited, and generally mild to moderate in the NGX-4010 group and less frequent and severe in the controls.
The study showed that one 60-min application of NGX-4010 provided rapid and sustained pain relief in patients with postherpetic neuralgia.
No adverse events were associated with treatment except for local reactions at the site of application and those related to treatment-associated pain.
Further studies by Backonja et al. ( 2010 ) found NGX-4010 (high concentration capsain patch) to be a promising topical treatment for postherpetic neuralgia patients and to be tolerable, generally safe, and effective.
During days 8–28 after the double-blind treatment, NGX-4010 patients had a mean change in numerical pain rating scale (NPRS) scores from baseline of –32.7% compared with –4.4% for control patients.
A similar decrease in NPRS scores from baseline was maintained with subsequent NGX-4010 treatments, regardless of the number of treatments received. Transient increases in application site pain were adequately managed with analgesics.
No increases in application site reactions or adverse events were observed with repeated treatments.
An open label study of 106 patients with moderate to severe postherpetic neuralgia (PHN) and painful human immunode fi ciency virus-associated distal sensory polyneuropathy (HIV-DSP) showed that that repeated treatments with NGX-4010, a high-concentration capsaicin patch (capsaicin 8%), was found to be generally safe and well tolerated (Simpson et al. 2010 ) .
The most frequently reported treatment-emergent adverse events were transient, mild-to-moderate application site erythema, pain, edema, and papules.
Small, transient pain-related increases in blood pressure during and immediately after NGX-4010 application were observed.
There was no evidence of an increased incidence of adverse events, dermal irritation, intolerability, or impaired neurological function with repeated treatments.
Peppin et al. ( 2011 ) found that transient patch application-related pain with NGX4010 (a capsaicin 8% dermal patch) could be managed with local cooling and/or oral analgesics in nearly all cases.
Patient adherence to the full intended treatment duration indicated that patch application-related pain was not a barrier to NGX-4010 use. In pivotal, randomized, double-blind, multicentre trials in adults with non-diabetic peripheral neuropathic pain, a single 60-min application of capsaicin dermal patch (8% capsaicin) reduced the mean numeric pain rating scale (NPRS) scores from baseline to a signi fi cantly greater extent than a low-concentration (0.04% w/w capsaicin) control patch during weeks 2–8 (McCormack 2010 ) .
In randomized, doubleblind, multicentre trials in patients with HIVassociated neuropathy, capsaicin dermal patch reduced the mean NPRS scores from baseline significantly more than control in one study for the 30- and 90-min, but not the 60-min, application during weeks 2–12. In another study, the differences between capsaicin (30- and 60-min applications) and control did not reach statistical signi fi cance.
An integrated analysis of both studies showed that the 30-min application of capsaicin dermal patch was significantly better than control for the reduction from baseline in mean NPRS scores during weeks 2–12.
The efficacy of capsaicin dermal patch was maintained for up to 1 year in extension studies in which patients could receive up to three or four repeat treatments.
Capsaicin dermal patch was generally well tolerated in clinical trials. The most common adverse events were transient, mostly mild to moderate, application-site reactions.
Capsaicin had also been reported to have proven ef fi cacy as a topical treatment for painful diabetic peripheral neuropathy (Tesfaye et al. 2011 ) .
Capsaicin is not generally recognized as safe and effective by the U.S. Food and Drug Administration for fever blister and cold sore treatment, but is considered to be safe and effective as an external analgesic counterirritant (Anonymous 2007 ) .
A patch containing 8% capsaicin (research code NGX-4010 and marketed under the trade name Qutenza( ® )), approved both in the EU and USA, provides a localized therapy with effects for neuralgia lasting up to 12 weeks after a single 60-min application based clinical trial evidence on the safety, ef fi cacy and unique attributes of this capsaicin 8% patch. (Wallace and Pappagallo 2011 ) .
The FDA has approved a topical 8% patch formulation of capsaicin (Qutenza-NeurogesX), available only by prescription, for local treatment of postherpetic neuralgia (Anonymous 2011 ) .
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antiobesity/weight lost activity
Tools for obesity management, including caffeine, ephedrine, capsaicin, and green tea have been proposed as strategies for weight loss and weight maintenance, since they may increase energy expenditure (4–5%), fat oxidation (10–16%) and have been proposed to counteract the decrease in metabolic rate that is present during weight loss (Diepvens et al. 2007 ; Hursel and WesterterpPlantenga 2010 ) .
Consumption of red chilli pepper had been reported to increase metabolic rate (Henry and Emery 1986 ) and such an increase in metabolic rate is now widely referred to as the thermic effect (TE) of food or diet-induced thermogenesis (DIT) (Rothwell and Stock 1981 ) .
Daily increases in thermogenesis of approximately 300–400 kJ can eventually lead to substantial weight loss (Hursel and Westerterp-Plantenga 2010 ).
Thermogenic ingredients may be considered as functional agents that could help in preventing a positive energy balance and obesity.
Cameron-Smith et al. ( 1990 ) reported the capsaicinoid spice principles capsaicin and dihydrocapsaicin to be thermogenic in the isolated rat hindlimb perfused with constant flow. Both principles elicited similar maximal increases in oxygen consumption (VO2) and perfusion pressure.
Their findings suggested that capsaicin and dihydrocapsaicin could be thermogenic in the rat and that the mechanism of action directly involved vasoconstriction in some manner.
Studies by Lim et al. ( 1979 ) suggested that hot red pepper ingestion stimulated carbohydrate oxidation at rest and during exercise in long distance male runners 18–23 year of age.
The meal with hot red pepper significantly elevated respiratory quotient and blood lactate levels at rest and during exercise.
Oxygen consumption at rest was slightly but non-significantly higher in the hot red pepper meal at 30 min after the meal.
Plasma epinephrine and norepinephrine levels were signi fi cantly higher in those who had only hot red pepper at 30 min after the meal. In a 3-way crossover, randomised, placebocontrolled, double-blinded intervention study of 19 overweight to obese, a diet supplement containing bioactive food ingredients (a combination of capsaicin, green tea extract (catechins and caffeine), tyrosine, and calcium) increased daily energy expenditure by approximately 200 kJ or 2%, without raising the heart rate or any observed adverse effects (Belza and Jessen 2005 ) .
The lack of effect of the enterocoated preparation suggested that a local action of capsaicin in the gastric mucosa was a prerequisite for exerting the thermogenic effect.
In a placebocontrolled, double-blind 8-week intervention study of 80 obese subjects, ingestion of a supplement containing a combination of tyrosine, capsaicin, catechines and caffeine was found to stimulate the sympathetic nervous system and promote satiety, lipolysis and thermogenesis (Belza et al. 2007 ) .
The bioactive supplement increased 4-hour thermogenesis by 90 kJ more than placebo, and the effect was maintained after 8 weeks and accompanied by a slight reduction in fat mass.
The bioactive supplement had no effect on faecal fat excretion, blood pressure or heart rate. The scientists concluded that these bioactive components may support weight maintenance after a hypocaloric diet.
Consumption of red chilli pepper had been reported to increase metabolic rate (Henry and Emery 1986 ) and such an increase in metabolic rate is now widely referred to as the thermic effect (TE) of food or diet-induced thermogenesis (DIT) (Rothwell and Stock 1981 ) .
Daily increases in thermogenesis of approximately 300–400 kJ can eventually lead to substantial weight loss (Hursel and Westerterp-Plantenga 2010 ).
Thermogenic ingredients may be considered as functional agents that could help in preventing a positive energy balance and obesity.
Cameron-Smith et al. ( 1990 ) reported the capsaicinoid spice principles capsaicin and dihydrocapsaicin to be thermogenic in the isolated rat hindlimb perfused with constant flow. Both principles elicited similar maximal increases in oxygen consumption (VO2) and perfusion pressure.
Their findings suggested that capsaicin and dihydrocapsaicin could be thermogenic in the rat and that the mechanism of action directly involved vasoconstriction in some manner.
Studies by Lim et al. ( 1979 ) suggested that hot red pepper ingestion stimulated carbohydrate oxidation at rest and during exercise in long distance male runners 18–23 year of age.
The meal with hot red pepper significantly elevated respiratory quotient and blood lactate levels at rest and during exercise.
Oxygen consumption at rest was slightly but non-significantly higher in the hot red pepper meal at 30 min after the meal.
Plasma epinephrine and norepinephrine levels were signi fi cantly higher in those who had only hot red pepper at 30 min after the meal. In a 3-way crossover, randomised, placebocontrolled, double-blinded intervention study of 19 overweight to obese, a diet supplement containing bioactive food ingredients (a combination of capsaicin, green tea extract (catechins and caffeine), tyrosine, and calcium) increased daily energy expenditure by approximately 200 kJ or 2%, without raising the heart rate or any observed adverse effects (Belza and Jessen 2005 ) .
The lack of effect of the enterocoated preparation suggested that a local action of capsaicin in the gastric mucosa was a prerequisite for exerting the thermogenic effect.
In a placebocontrolled, double-blind 8-week intervention study of 80 obese subjects, ingestion of a supplement containing a combination of tyrosine, capsaicin, catechines and caffeine was found to stimulate the sympathetic nervous system and promote satiety, lipolysis and thermogenesis (Belza et al. 2007 ) .
The bioactive supplement increased 4-hour thermogenesis by 90 kJ more than placebo, and the effect was maintained after 8 weeks and accompanied by a slight reduction in fat mass.
The bioactive supplement had no effect on faecal fat excretion, blood pressure or heart rate. The scientists concluded that these bioactive components may support weight maintenance after a hypocaloric diet.
Antihemostatic and Antithrombotic
Activities
Capsaicin was found to dose-dependently prolong the tail bleeding time in the conscious mice after the oral administration (Wang et al. 1985 ) .
Capsaicin was effective in preventing death caused by adenosine diphosphate-induced acute pulmonary thromboembolism in mice at dose of 25 mg/kg, while aspirin and indomethacin had no effect at 200 mg/kg.
Capsaicin also reduced the mortality in collagen- and sodium arachidonate-induced thromboembolic death at dose of 25 and 50 mg/kg, respectively, and aspirin and indomethacin were also effective in these models but only when the dose was higher than 200 mg/kg.
Capsaicin also suppressed platelet aggregation significantly, but did not affect blood coagulation.
The scientists concluded that capsaicin was proven to be more effective than aspirin and indomethacin in preventing the death of acute pulmonary thromboembolism, and this effect could be due to its inhibition on platelet aggregation.
Cardiovascular studies of on blood vessels showed that both capsaicinoids and capsaicin (extracted from C. frutescens fruit) could inhibit vasoconstriction induced by norepinephrine and the vasodilatation effect of capsaicinoids might be due to the action of capsaicin (Jaiarj et al. 1998 ) .
Both capsaicinoids and capsaicin were found to cause significant decrease in platelet aggregation induced by adenosine diphosphate and collagen.
Comparison of capsaicin with capsaicinoid extract having the same amount of capsaicin revealed that capsaicin had higher antiplatelet aggregating activity than capsaicinoids.
This indicated that there might be other substances in the mixture which could decrease the antiplatelet aggregating effect.
Capsaicin was effective in preventing death caused by adenosine diphosphate-induced acute pulmonary thromboembolism in mice at dose of 25 mg/kg, while aspirin and indomethacin had no effect at 200 mg/kg.
Capsaicin also reduced the mortality in collagen- and sodium arachidonate-induced thromboembolic death at dose of 25 and 50 mg/kg, respectively, and aspirin and indomethacin were also effective in these models but only when the dose was higher than 200 mg/kg.
Capsaicin also suppressed platelet aggregation significantly, but did not affect blood coagulation.
The scientists concluded that capsaicin was proven to be more effective than aspirin and indomethacin in preventing the death of acute pulmonary thromboembolism, and this effect could be due to its inhibition on platelet aggregation.
Cardiovascular studies of on blood vessels showed that both capsaicinoids and capsaicin (extracted from C. frutescens fruit) could inhibit vasoconstriction induced by norepinephrine and the vasodilatation effect of capsaicinoids might be due to the action of capsaicin (Jaiarj et al. 1998 ) .
Both capsaicinoids and capsaicin were found to cause significant decrease in platelet aggregation induced by adenosine diphosphate and collagen.
Comparison of capsaicin with capsaicinoid extract having the same amount of capsaicin revealed that capsaicin had higher antiplatelet aggregating activity than capsaicinoids.
This indicated that there might be other substances in the mixture which could decrease the antiplatelet aggregating effect.
anti-venom activity
The macerated ripe fruits of Capsicum frutescens exhibited moderate neutralizing ability against the haemorrhagic effect of Bothrops atrox venom (Otero et al. 2000 ) .
anti-psoriasis activity
Capsicum frutescens was reported to be an effective treatment for psoriasis (Reuter et al. 2010 ) .
gastroprotective activity
Capsaicin (0.1 and 0.5 mg/kg, p.o.) inhibited absolute ethanol-induced gastric lesion formation in rats in a dose-dependent manner (Uchida et al. 1991 ) .
The protective effect of capsaicin was attenuated by indomethacin-pretreatment and disappeared in capsaicin-sensitive nerve degenerated rats.
Capsaicin did not induce the distension of gastric mucosal folds. Their results suggested that stimulation of capsaicin-sensitive afferent nerves by capsaicin would enhance the prostaglandin formation, leading to an inhibition of gastric lesions.
Treatment with small doses of topical capsaicin was found to protect the gastric mucosa from the damage by strong irritants but functional ablation of sensory nerves by pretreatment with larger dose of parenteral capsaicin augmented the formation of gastric lesions (Brzozowski et al. 1996 ) .
The scientists found that pretreatment with i.g.(intragastric) capsaicin (0.12–1.0 mg/kg) in rats with intact sensory nerves (series A) reduced dose-dependently the mucosal damage caused by absolute ethanol, acidi fi ed aspirin (ASA) or water immersion and restraint stress (WRS).
This protection was accompanied by a significant rise in gastric mucosal blood flow (GBF).
Parenteral application of capsaicin (1.2–10 mg/kg s.c.) in intact rats dose-dependently increased GBF, and also dosedependently reduced gastric damage induced by ASA or WRS (but not by ethanol) but this effect was reversed by indomethacin at a dose that suppressed endogenous prostaglandins biosynthesis by about 90%, indicating that prostaglandins were involved in the protective activities of topical capsaicin.
Capsaicin deactivation of sensory nerves aggravated mucosal lesions induced by all three ulcerogens and this effect was accompanied by a marked decrease in GBF.
In such capsaicin-deactivated rats, topical capsaicin also reduced ethanol-, ASA- or WRS-induced lesions, while parenteral capsaicin was effective only in the protection against the damage induced by acidi fi ed ASA and WRS but not by ethanol.
They concluded that capsaicin was capable of protecting gastric mucosa in rats with both intact and capsaicin-deactivated rats and that this protective activity depended, at least in part, upon its hyperemic and antisecretory effects that may be mediated, at least in part, by endogenous release of prostaglandins.
Abdel-Salam et al. ( 1997 ) stated in their review that experimental data provided clear evidence indicating capsaicin-sensitive (CS) sensory nerves to be involved in a local defense mechanism against gastric ulcer in the rat abdomen.
Stimulation of CS sensory nerves with low intragastric concentrations of capsaicin protected the rat gastric mucosa against injury produced by different ulcerogenic agents. In contrast, high local desensitizing concentrations of capsaicin or systemic neurotoxic doses of the agent markedly enhanced the susceptibility of the rat gastric mucosa to later noxious challenge.
Resiniferatoxin, a potent analogue of capsaicin also possessed an acute gastroprotective effect similar to that of capsaicin in the stomach.
The gastroprotective effect of capsaicin-type agents involved an enhancement of the microcirculation effected through the release of mediator peptides from the sensory nerve terminals with calcitonin generelated peptide being the most likely candidate implicated.
They stated that capsaicin-sensitive fi bres were involved in the repair mechanisms of the gastric mucosa. A protective role for CS sensory nerves had also been demonstrated in the colon.
In most studies, capsaicin introduced into the stomach of rats or cats inhibited gastric acid secretion.
In humans, recent studies also provided evidence in favour of a beneficial effect of capsaicin on the gastric mucosa but an exact concentration-related assessment of the effect of the agent was still lacking.
In another study they found that introduction of capsaicin into the rat stomach in very low concentrations of ng- m g/mL range protected the gastric mucosa against damage produced by topical acidi fi ed aspirin, indomethacin, ethanol or 0.6 N HCl.
Resiniferatoxin exhibited acute gastroprotective effect similar to that of capsaicin (Abdel-Salam et al. 1999 ) .
Capsaicin given into the stomach in higher desensitizing concentrations of 6.5 mM markedly enhanced the susceptibility of the gastric mucosa and invariably aggravated gastric mucosal damage evoked by later noxious challenge.
Such high desensitizing concentrations of capsaicin, however, did not reduce the cytoprotective effect of prostacyclin (PGI2) or beta-carotene.
Capsaicin or resiniferatoxin had an additive protective effect to that of atropine or cimetidine.
They concluded that the gastroprotective effect of capsaicin-type agents involved primarily an enhancement of the microcirculation effected through local release of mediator peptides from the sensory nerve terminals. A reduction in gastric acidity may contribute to some degree in the gastric protective action of capsaicin-type agents.
The vasodilator and gastroprotective effects of capsaicin-type agents were not dependent on vagal efferents or sympathetic neurons, but involved prostanoids, histaminergic or cholinergic pathways. In another review, Szolcsányi and Barthó ( 2001 ) stated that capsaicin-sensitive peptidergic afferents plays a pivotal role in the maintenance of gastric mucosal integrity against injurious interventions.
They stated that recent evidence indicated that the gastroprotective effect of capsaicin in the human stomach involved additional mechanisms to those already revealed in the rat such as :
- (1) the existence of capsaicin-sensitive afferents with both sensory and mediator releasing functions in the rat stomach;
- (2) VR-1 agonists (capsaicin, resiniferatoxin, piperine) protected against gastric ulcer of the rat parallel with their sensory stimulating potencies;
- (3) antidromic stimulation of capsaicin-sensitive vagal and somatic afferents resulted in the release of CGRP (calcitonin generelated peptide), tachykinins, NO and somatostatin.
Mózsik et al. ( 2001 ) reported on four response stages of capsaicin-sensitive primary afferents to capsaicin: excitation, a sensory-blocking effect, long-term selective neurotoxic impairment and irreversible cell destruction. These responses were dependent on the dosage and timing of capsaicin.
Capsaicin and its analog inhibited the development of different chemically induced gastric mucosal damage in various experimental models if they were given intragastric doses ( m g/ kg).
Mózsik et al. ( 2005 ) reported on the gastroprotective effect of low concentration of capsaicin against the ethanol- and indomethacin (IND)- induced gastric mucosal damage in healthy human subjects.
Intragastric application of capsaicin decreased gastric acid secretion basal acid output and enhanced “non-parietal” component, gastric transmucosal potential difference (GTPD) in a dose-dependent manner.
The decrease of GTPD evoked by ethanol was inhibited by the capsaicin application, which was reproducible. The gastroprotective effect of capsaicin was attributed to stimulation of the sensory nerve endings.
gastric secretion stimulation activity
A mixture of red pepper suspension ( Capsicum frutescens ) and α-alanine (an amino-acid) mixture caused an increase of gastric acid in 33 duodenal ulcer and 18 non-duodenal ulcer patients (Solanke et al. 1976 ) .
The administration of α-alanine in red pepper suspension produced less gastric acid than the fresh red pepper suspension alone.
Aqueous extracts of Capsicum annuum or Capsicum frutescens induced gastric acid secretion dose-dependently when administered to urethane anaesthetized albino rats of both sexes (Sambo et al. 2007 ) .
Gastric acid secretion stimulation was mediated by H2 receptor stimulation. Under conditions whereby the stomach (acid secretion was inhibited by omeprazole given i.p.) or the duodenum was perfused with saline (pH 4.5), mucosal application of capsaicin (0.3–6 mg/ mL for 30 min) caused significantly increased pH and HCO 3 - output in a concentration-related manner in both tissues, while transmucosal potential difference increased in the duodenum and decreased in the stomach of anaesthetized rats (Takeuchi et al 1992 ) .
The results indicated that mucosal application of capsaicin increased the gastroduodenal HCO 3 - output by stimulation of capsaicin-sensitive sensory neurons and that the action may be in part mediated by endogenous prostaglandins.
The administration of α-alanine in red pepper suspension produced less gastric acid than the fresh red pepper suspension alone.
Aqueous extracts of Capsicum annuum or Capsicum frutescens induced gastric acid secretion dose-dependently when administered to urethane anaesthetized albino rats of both sexes (Sambo et al. 2007 ) .
Gastric acid secretion stimulation was mediated by H2 receptor stimulation. Under conditions whereby the stomach (acid secretion was inhibited by omeprazole given i.p.) or the duodenum was perfused with saline (pH 4.5), mucosal application of capsaicin (0.3–6 mg/ mL for 30 min) caused significantly increased pH and HCO 3 - output in a concentration-related manner in both tissues, while transmucosal potential difference increased in the duodenum and decreased in the stomach of anaesthetized rats (Takeuchi et al 1992 ) .
The results indicated that mucosal application of capsaicin increased the gastroduodenal HCO 3 - output by stimulation of capsaicin-sensitive sensory neurons and that the action may be in part mediated by endogenous prostaglandins.
mitogenic activity
A monomeric mannose/glucose-binding lectin, with a molecular mass of 29.5 kDa and an N-terminal sequence GQRELKL showing resemblance to that of the lectin-like oxidized lowdensity lipoprotein receptor from the rabbit, was isolated from the seeds of red cluster pepper Capsicum frutescens var. fasciculatum (Ngai and Ng 2001 ) .
The lectin showed strong mitogenic activity toward spleen cells isolated from BALB/c mice. The mitogenic activity, which reached a peak at a lectin concentration of 0.27 m M,
The lectin showed strong mitogenic activity toward spleen cells isolated from BALB/c mice. The mitogenic activity, which reached a peak at a lectin concentration of 0.27 m M,
aflatoxin contamination
Samples of sundried, matured red pepper, Capsicum annum were found to have on a dry weight basis 12.7–26.8% moisture content, 5.0– 6.4 mg/100 g vitamin C, 0.8–1.2% crude protein, 3.3–4.1% total soluble solids, and fungal counts of log 4.4–4.5/g (Adegoke et al. 1996 ) .
Ordinary matured red C. annum had 75.7–78.2% moisture content, 36.1–38.5 mg/100 g vitamin C, 2.4–2.8% crude protein, 9.3–9.9% total soluble solids, and fungal count of log 3.32–3.39/g.
Sundried matured red C. frutescens had corresponding values of 9.4–18.7%, 5.8–6.3 mg/100 g, 0.8–1.1, 0.9–2.6% and fungal counts log 3.2–3.4/g. No aflatoxins were detected in sundried, matured red C. frutescens , but aflatoxin B1 values obtained from C. annum varied from non-detectable to 2.2 m g/kg.
Dominant fungi isolated from C. annum and C. frutescens were Rhizopus oryzae , Aspergillus niger , A. fl avus , Geotrichum candidum and Saccharomyce s spp.
Ordinary matured red C. annum had 75.7–78.2% moisture content, 36.1–38.5 mg/100 g vitamin C, 2.4–2.8% crude protein, 9.3–9.9% total soluble solids, and fungal count of log 3.32–3.39/g.
Sundried matured red C. frutescens had corresponding values of 9.4–18.7%, 5.8–6.3 mg/100 g, 0.8–1.1, 0.9–2.6% and fungal counts log 3.2–3.4/g. No aflatoxins were detected in sundried, matured red C. frutescens , but aflatoxin B1 values obtained from C. annum varied from non-detectable to 2.2 m g/kg.
Dominant fungi isolated from C. annum and C. frutescens were Rhizopus oryzae , Aspergillus niger , A. fl avus , Geotrichum candidum and Saccharomyce s spp.
Cytopathic/Carcinogenic/Clastogenic/
Genotoxic Effects/Toxicological
Studies
Although capsaicin had been reported to exhibit antitumour activity, carcinogenic and mutagenic potential had also been reported but results of studies had been con fl icting (Surh and Lee 1995 ) .
Toth et al. ( 1984 ) found that capsaicin-treated Swiss albino mice (10%) developed adenocarcinomas of the duodenum while no such tumour occurred in the untreated control mice.
Capsaicin exhibited a low level of mutagenicity in the Ames assay with Salmonella typhimurium strain TA98 in the presence of liver activating enzymes from Aroclor-induced rats. A crude mixture of capsaicinoids from Capsicum frutescens , capsaicin and dihydrocapsaicin (DC) but not 4-methyldihydrocapsaicin, a synthetic homolog of DC, were mutagenic in the Chinese hamster lung fibroblast V79 cell assay (Lawson and Gannett 1989 ) .
Chilli extract and capsaicin were found to be mutagenic in Salmonella typhimurium histidine-de fi cient tester strains TA 98, TA 100, TA 1535, TA 1537, and TA 1538 with metabolic activation, with capsaicin being more potent (Nagabhushan and Bhide 1985 ) . Both were negative in the V79 Chinese hamster cell assay.
In the micronucleus test, only capsaicin was positive near the LD 50 dose. Capsaicin also inhibited DNA synthesis in the testes of Swiss mice injected at two dose levels.
In-vivo studies using the mouse-bone-marrow micronucleus (mouse-MN) assay showed C. frutescens fruit extract to have clastogenic activity similar to that that of tetracycline, a known clastogen (Villaseñor and de Ocampo 1994 ) .
Chilli ( Capsicum frutescens ) extract was found to inhibit proliferation of human buccal mucosa fibroblast cell at concentrations of 300–500 m g/ mL (Van Wyk et al. 1995 ) .
Total cell death occurred at 16 days with 300 m g/mL and at 6 days with 400–500 m g/mL. The cytopathic effect of chilli extract to fibroblasts was concentration dependent.
Oikawa et al. ( 2006 ) reported that capsaicin induced oxidative damage in the presence of metal ion and various kinds of cytochrome P450 (CYP).
They concluded that Cu(II)- mediated oxidative DNA damage by CYP-treated capsaicin would be relevant for the expression of its carcinogenicity.
Capsaicin, at non-toxic amounts of 0.25 and 0.5 m mole/plate, expressed a dose-dependent inhibition of the mutagenicity of heterocyclic amines Glu-P-1 and PhIP in Salmonella typhimurium TA98 when they were metabolically activated by rat, hamster and human liver S9 and of heterocyclic amine Trp-P-2 when activated by rat and hamster liver S9 (Huynh and Teel 2005 ) .
In contrast, capsaicin enhanced the mutagenicity of Trp-P-2 in Salmonella typhimurium TA98 when incubated with human liver S9. The lack of consistency in the anti-mutagenic action of capsaicin toward heterocyclic amines was unresolved.
In a study of 114 consecutive patients with confirmed gallbladder cancer, diagnosed 1992– 1995, significant red chili pepper consumption was observed in gallbladder cancer patients (Serra et al. 2002 ) .
Multivariate analysis deemed only a very low socioeconomic status and red chili pepper consumption as significant independent risk factors for gallbladder cancer.
Subsequent studies showed that pure capsaicin did not show mutagenic activity in Salmonella typhimurium strain TA98 with without metabolic activation (S9 mix) (Tsuchiya et al. 2011 ) .
Aflatoxin contamination of red chili pepper was confirmed, and the concentrations of a fl atoxins B1 and G1 were 4.4 and 0.5 ng/g, respectively.
Their findings suggested that low-level but protracted exposure to aflatoxins may be associated with the development of gallbladder cancer in Chilean women who carry gallstones.
A single topical application of capsaicin (10 m mol) followed by twice-weekly applications of
12- O-tetradecanoylphorbol-13-acetate onto shaven backs of female ICR mice resulted in no significant increases in incidence and multiplicity of skin tumours, compared with the solventpretreated control animals (Park and Surh 1997 ) .
Repeated topical applications of capsaicin alone failed to promote 7,12-dimethylbenz[a]anthracene-initiated mouse skin tumorigenesis, but moderately inhibited the papilloma formation when given prior to each topical dose of phorbol ester.
Studies showed that male Wistart rats fed a commercial diet mixed with 2% ground Capsicum frutescens fruits for 8 weeks did not adversely affect general health, body weight gain, feed intake and feed efficiency (al-Qarawi and Adam 1999 ) .
The feed intake and growth rate were depressed and exfoliation of the intestinal epithelium into the lumen and cytoplasmic fatty vacuolation and necrosis of the centrilobular hepatocytes occurred at 4 and 8 weeks in rats fed with 10% Capsicum .
This correlated with changes in hematology, serum enzyme profiles and other serum constituents.
Rats fed the 10% C. frutescens diet exhibited impaired growth but did not develop nephropathy nor diarrhoea; in contrast body weight loss, inef fi ciency of feed utilization, diarrhoea, and enterohepatonephropathy characterized Citrullus colocynthis toxicosis in rats (AL-Qarawi and Adam 2003 ) .
Feeding the mixture of C. frutescens and C. colocynthis caused more pronounced effects and death of rats. Vital organ lesions accompanied by anaemia and leucopenia were correlated with changes in serum ALP, AST and ALT activities with alterations in concentrations of total protein, albumin, urea and other serum constituents.
Studies by Chanda et al. ( 2004 ) showed that the genotoxic potential of pure trans -capsaicin was very low.
In the Ames assay, pure trans - capsaicin was not mutagenic to Salmonella typhimurium or Escherichia coli when tested at concentrations extending into the toxic range but was weakly mutagenic in mouse lymphoma L5178Y cells, in the presence of S9 mix. Trans - capsaicin did not induce micronuclei in bone marrow cells when tested to the maximum tolerated dose of 800 mg/kg/day in male and 200 mg/ kg/day in female CD-1 mice.
Trans -capsaicin did not induce structural or numerical chromosomal aberrations when evaluated for its ability to induce clastogenicity in blood lymphocytes.
They added the purity and source of capsaicin should always be an important consideration for toxicological evaluations.
The results of a series of standard assays performed in accordance with the Organisation for Economic Cooperation and Development guidance, confirmed the absence of genotoxic activity of high-purity capsaicin in the bacterial mutation and chromosome aberration tests (Proudlock et al. 2004 ) .
In addition, no evidence of cytotoxicity or genotoxicity was seen in the rat bone marrow micronucleus test, where systemic exposure to pure capsaicin was achieved using the subcutaneous route and a rising dose toleration protocol.
They added that earlier reported in-vitro genotoxic activity was probably associated with mutagenic impurities in commercial grades of the material.
Capsicum and paprika are generally recognized as safe by the U.S. Food and Drug Administration for use in food (Anonymous 2007 ) .
Based on provocative and predictive investigations in human subject, capsaicin could be irritating at low concentrations; its double edge sword effects of being anticarcinogenic and antigenotoxic, and also carcinogenic and genotoxic, and that capsaicin enhanced the penetration of an antiin fl ammatory agent through human skin, the Panel recommends that care should be exercised in using ingredients that contain capsaicin in cosmetic products (Anonymous 2007 ) .
Toth et al. ( 1984 ) found that capsaicin-treated Swiss albino mice (10%) developed adenocarcinomas of the duodenum while no such tumour occurred in the untreated control mice.
Capsaicin exhibited a low level of mutagenicity in the Ames assay with Salmonella typhimurium strain TA98 in the presence of liver activating enzymes from Aroclor-induced rats. A crude mixture of capsaicinoids from Capsicum frutescens , capsaicin and dihydrocapsaicin (DC) but not 4-methyldihydrocapsaicin, a synthetic homolog of DC, were mutagenic in the Chinese hamster lung fibroblast V79 cell assay (Lawson and Gannett 1989 ) .
Chilli extract and capsaicin were found to be mutagenic in Salmonella typhimurium histidine-de fi cient tester strains TA 98, TA 100, TA 1535, TA 1537, and TA 1538 with metabolic activation, with capsaicin being more potent (Nagabhushan and Bhide 1985 ) . Both were negative in the V79 Chinese hamster cell assay.
In the micronucleus test, only capsaicin was positive near the LD 50 dose. Capsaicin also inhibited DNA synthesis in the testes of Swiss mice injected at two dose levels.
In-vivo studies using the mouse-bone-marrow micronucleus (mouse-MN) assay showed C. frutescens fruit extract to have clastogenic activity similar to that that of tetracycline, a known clastogen (Villaseñor and de Ocampo 1994 ) .
Chilli ( Capsicum frutescens ) extract was found to inhibit proliferation of human buccal mucosa fibroblast cell at concentrations of 300–500 m g/ mL (Van Wyk et al. 1995 ) .
Total cell death occurred at 16 days with 300 m g/mL and at 6 days with 400–500 m g/mL. The cytopathic effect of chilli extract to fibroblasts was concentration dependent.
Oikawa et al. ( 2006 ) reported that capsaicin induced oxidative damage in the presence of metal ion and various kinds of cytochrome P450 (CYP).
They concluded that Cu(II)- mediated oxidative DNA damage by CYP-treated capsaicin would be relevant for the expression of its carcinogenicity.
Capsaicin, at non-toxic amounts of 0.25 and 0.5 m mole/plate, expressed a dose-dependent inhibition of the mutagenicity of heterocyclic amines Glu-P-1 and PhIP in Salmonella typhimurium TA98 when they were metabolically activated by rat, hamster and human liver S9 and of heterocyclic amine Trp-P-2 when activated by rat and hamster liver S9 (Huynh and Teel 2005 ) .
In contrast, capsaicin enhanced the mutagenicity of Trp-P-2 in Salmonella typhimurium TA98 when incubated with human liver S9. The lack of consistency in the anti-mutagenic action of capsaicin toward heterocyclic amines was unresolved.
In a study of 114 consecutive patients with confirmed gallbladder cancer, diagnosed 1992– 1995, significant red chili pepper consumption was observed in gallbladder cancer patients (Serra et al. 2002 ) .
Multivariate analysis deemed only a very low socioeconomic status and red chili pepper consumption as significant independent risk factors for gallbladder cancer.
Subsequent studies showed that pure capsaicin did not show mutagenic activity in Salmonella typhimurium strain TA98 with without metabolic activation (S9 mix) (Tsuchiya et al. 2011 ) .
Aflatoxin contamination of red chili pepper was confirmed, and the concentrations of a fl atoxins B1 and G1 were 4.4 and 0.5 ng/g, respectively.
Their findings suggested that low-level but protracted exposure to aflatoxins may be associated with the development of gallbladder cancer in Chilean women who carry gallstones.
A single topical application of capsaicin (10 m mol) followed by twice-weekly applications of
12- O-tetradecanoylphorbol-13-acetate onto shaven backs of female ICR mice resulted in no significant increases in incidence and multiplicity of skin tumours, compared with the solventpretreated control animals (Park and Surh 1997 ) .
Repeated topical applications of capsaicin alone failed to promote 7,12-dimethylbenz[a]anthracene-initiated mouse skin tumorigenesis, but moderately inhibited the papilloma formation when given prior to each topical dose of phorbol ester.
Studies showed that male Wistart rats fed a commercial diet mixed with 2% ground Capsicum frutescens fruits for 8 weeks did not adversely affect general health, body weight gain, feed intake and feed efficiency (al-Qarawi and Adam 1999 ) .
The feed intake and growth rate were depressed and exfoliation of the intestinal epithelium into the lumen and cytoplasmic fatty vacuolation and necrosis of the centrilobular hepatocytes occurred at 4 and 8 weeks in rats fed with 10% Capsicum .
This correlated with changes in hematology, serum enzyme profiles and other serum constituents.
Rats fed the 10% C. frutescens diet exhibited impaired growth but did not develop nephropathy nor diarrhoea; in contrast body weight loss, inef fi ciency of feed utilization, diarrhoea, and enterohepatonephropathy characterized Citrullus colocynthis toxicosis in rats (AL-Qarawi and Adam 2003 ) .
Feeding the mixture of C. frutescens and C. colocynthis caused more pronounced effects and death of rats. Vital organ lesions accompanied by anaemia and leucopenia were correlated with changes in serum ALP, AST and ALT activities with alterations in concentrations of total protein, albumin, urea and other serum constituents.
Studies by Chanda et al. ( 2004 ) showed that the genotoxic potential of pure trans -capsaicin was very low.
In the Ames assay, pure trans - capsaicin was not mutagenic to Salmonella typhimurium or Escherichia coli when tested at concentrations extending into the toxic range but was weakly mutagenic in mouse lymphoma L5178Y cells, in the presence of S9 mix. Trans - capsaicin did not induce micronuclei in bone marrow cells when tested to the maximum tolerated dose of 800 mg/kg/day in male and 200 mg/ kg/day in female CD-1 mice.
Trans -capsaicin did not induce structural or numerical chromosomal aberrations when evaluated for its ability to induce clastogenicity in blood lymphocytes.
They added the purity and source of capsaicin should always be an important consideration for toxicological evaluations.
The results of a series of standard assays performed in accordance with the Organisation for Economic Cooperation and Development guidance, confirmed the absence of genotoxic activity of high-purity capsaicin in the bacterial mutation and chromosome aberration tests (Proudlock et al. 2004 ) .
In addition, no evidence of cytotoxicity or genotoxicity was seen in the rat bone marrow micronucleus test, where systemic exposure to pure capsaicin was achieved using the subcutaneous route and a rising dose toleration protocol.
They added that earlier reported in-vitro genotoxic activity was probably associated with mutagenic impurities in commercial grades of the material.
Capsicum and paprika are generally recognized as safe by the U.S. Food and Drug Administration for use in food (Anonymous 2007 ) .
Based on provocative and predictive investigations in human subject, capsaicin could be irritating at low concentrations; its double edge sword effects of being anticarcinogenic and antigenotoxic, and also carcinogenic and genotoxic, and that capsaicin enhanced the penetration of an antiin fl ammatory agent through human skin, the Panel recommends that care should be exercised in using ingredients that contain capsaicin in cosmetic products (Anonymous 2007 ) .
traditional medicinal uses
C. frutescens and C. annuum have been used as :
and as folk remedies for :
(Burkill 1966 ; Grieve 1971 ; Bown 1995 ; Chevallier 1996 ; Chai 2006 ; Tolan et al. 2001 ; Stuart 2011 ).
In European medicine, pepper has been used as a carminative and stimulant to dispel fl atulence and to rouse appetite.
The fruit is used externally as a strong rubefacient stimulating the circulation, aiding the removal of waste products and increasing the fl ow of nutrients to the tissues.
As rubefacient, it is mixed with cotton-seed oil, applied as cataplasm or as liniment.
It has also been powdered and placed inside socks as a traditional remedy for those prone to cold feet.
In Peninsular Malaysia the fruit is used for diarrhoea, vomiting and dyspepsia.
It has also been administered applied internally after childbirth as a stimulant and is applied to the skin in childbirth as a counter-irritant. In Java the leaves are used instead of the fruit for this purpose.
It also has hypoglycemic properties.
In Sarawak, the Iban and Malay apply a paste of the leaves mixed with ashes for ringworm;
The Kenyah use pounded fruit and cooking ash to treat cuts and wounds;
The Bisayas rub pounded roots on the legs to counter black magical spells; and
The Melanau consume a leaf decotion to ease pain in urinating.
Capsicum frutescens has been used to treat diabetes mellitus by traditional healers in Jamaica.
The ancient Mayans have been reported to used it for treatment of coughs, sore throat and coughs.
A weak fruit infusion can be employed as a gargle to treat throat complaints.
Fruit juice is applied to the tooth cavity for toothache by the Aztecs.
A poultice of chilli pepper is used as a poultice over affected rheumatic parts.
Applied to the skin it desensitizes nerve endings and so has been used as a local anaesthetic.
A strong fruit infusion is used as a remedy for scalp ringworm.
It has proved ef fi cacious in dilating blood vessels and thus relieving chronic congestion of people addicted to drink.
However, excessive consumption of red pepper may aggravate symptoms of duodenal ulcers and cause gastroenteritis and kidney damage.
- carminative,
- digestive irritant,
- stomachic,
- antihaemorrhoidal,
- antirheumatic,
- antiseptic,
- stimulant,
- rubefacient,
- antispasmodic,
- diaphoretic,
- stomachic,
- digestive,
- sialagogue and tonic
and as folk remedies for :
- dropsy,
- colic,
- diarrhea,
- asthma,
- arthritis,
- muscle cramps, and
- toothache
(Burkill 1966 ; Grieve 1971 ; Bown 1995 ; Chevallier 1996 ; Chai 2006 ; Tolan et al. 2001 ; Stuart 2011 ).
In European medicine, pepper has been used as a carminative and stimulant to dispel fl atulence and to rouse appetite.
The fruit is used externally as a strong rubefacient stimulating the circulation, aiding the removal of waste products and increasing the fl ow of nutrients to the tissues.
As rubefacient, it is mixed with cotton-seed oil, applied as cataplasm or as liniment.
It has also been powdered and placed inside socks as a traditional remedy for those prone to cold feet.
In Peninsular Malaysia the fruit is used for diarrhoea, vomiting and dyspepsia.
It has also been administered applied internally after childbirth as a stimulant and is applied to the skin in childbirth as a counter-irritant. In Java the leaves are used instead of the fruit for this purpose.
It also has hypoglycemic properties.
In Sarawak, the Iban and Malay apply a paste of the leaves mixed with ashes for ringworm;
The Kenyah use pounded fruit and cooking ash to treat cuts and wounds;
The Bisayas rub pounded roots on the legs to counter black magical spells; and
The Melanau consume a leaf decotion to ease pain in urinating.
Capsicum frutescens has been used to treat diabetes mellitus by traditional healers in Jamaica.
The ancient Mayans have been reported to used it for treatment of coughs, sore throat and coughs.
A weak fruit infusion can be employed as a gargle to treat throat complaints.
Fruit juice is applied to the tooth cavity for toothache by the Aztecs.
A poultice of chilli pepper is used as a poultice over affected rheumatic parts.
Applied to the skin it desensitizes nerve endings and so has been used as a local anaesthetic.
A strong fruit infusion is used as a remedy for scalp ringworm.
It has proved ef fi cacious in dilating blood vessels and thus relieving chronic congestion of people addicted to drink.
However, excessive consumption of red pepper may aggravate symptoms of duodenal ulcers and cause gastroenteritis and kidney damage.
other uses
C. frutescens cultivars can be used in chilli breeding for genetic improvement purposes.
Chilli pepper extracts and oleoresin are used in production of self-defence and less than-lethal (LTL) weaponry.
Hot pepper extracts has been found to repel to exhibit toxic and repellent effects against spider mites (Antonious et al. 2006b ) .
Capsaicin is also employed in a gel-based product as a feral pigeon deterrent from specific roosting and loa fi ng areas.
Chilli pepper extracts and oleoresin are used in production of self-defence and less than-lethal (LTL) weaponry.
Hot pepper extracts has been found to repel to exhibit toxic and repellent effects against spider mites (Antonious et al. 2006b ) .
Capsaicin is also employed in a gel-based product as a feral pigeon deterrent from specific roosting and loa fi ng areas.
comments
Some well-known cultivars of Capsicum frutescens encountered around the globe are:
- African Birdseye or African Devil (also called Piri-piri),
- Cabe Rawit,
- Chilli Padi,
- Demon Red,
- Kambuzi Pepper,
- Malagueta Pepper,
- Malawian Pepper Siling Labuyo,
- Tabasco Pepper.
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