Capsicum

Summary and Pharmaceutical Comment

Capsicum is commonly used in both foods and medicinal products. The capsaicinoids are principally responsible for the biological activity of capsicum. These pungent principles are thought to stimulate and aid digestion and to act as a counter-irritant when applied externally. Capsaicin has also been used as a neurochemical tool for studying sensory neurotransmission. Topical creams containing capsaicin 0.025% and 0.075% are licensed in the UK for symptomatic relief of osteoarthritis, and post-herpetic neuralgia, respectively. Capsicum oleoresin and capsaicin are ingredients of a number of over-the-counter (OTC) topical preparations for relief of pain in muscle, tendon and joints.

Conflicting reports have been documented concerning the effect of capsicum on acid secretion and on ulcer healing. Capsaicin-sensitive areas of the gastric and duodenal mucosa are thought to provide protection against mucosal damage. It has been suggested that this protection is lost if the sensory fibres are desensitised. Whether oral consumption of capsicum by humans can cause desensitisation is unclear. The toxicity of capsicum extracts observed in animals is considered to be due to the capsaicinoid components. However, ingestion of capsicum in the diet is not thought to represent a health risk. Capsicum should not be ingested in doses greatly exceeding amounts normally used in foods.

Species (Family)

Capsicum species (Solanaceae) including C. annum L., C. baccatum L., C. chinense Jacq., C. frutescens L., C. pubescens

Ruiz & Pavon, C. minimum Roxb.

Synonym(s)

Cayenne, Chilli Pepper, Hot Pepper, Paprika, Red Pepper, Tabasco

Pepper

Part(s) Used

Fruit

Pharmacopoeial and Other Monographs

BHP 1996(G9)

BP 2007(G84)

Complete German Commission E (Paprika)(G3)

Martindale 35th edition(G85)

Ph Eur 2007(G81)

USP29/NF24(G86)

C

Legal Category (Licensed Products)

GSL(G37)

Constituents

The following is compiled from several sources, including General References G22 and G41.

Capsaicinoids Up to 1.5%, usually 0.11%. Major components capsaicin (48.6%), 6,7-dihydrocapsaicin (36%), nordihydrocapsaicin (7.4%), homodihydrocapsaicin (2%) and homocapsaicin (2%).

Volatile oils Trace. Over 125 components have been isolated with at least 24 characterised.

Other constituents Carotenoid pigments (capsanthin, capsorubin, carotene, lutein), proteins (12–15%), fats (9–17%), vitamins including A and C.

Other plant parts The plant material contains solanidine, solanine and solasodine (steroidal alkaloidal glycosides) and scopoletin (coumarin).

Food Use

Capsicum (chilli) peppers are widely used as a spice. Capsicum is listed by the Council of Europe as a natural source of food flavouring (category N2). This category indicates that capsicum can be added to foodstuffs in small quantities, with a possible limitation of an active principle (as yet unspecified) in the final

product.(G16) Previously, capsicum has been stated to be GRAS (Generally Recognised As Safe).(G41)

126 Capsicum

Herbal Use

Capsicum is stated to possess stimulant, antispasmodic, carminative, diaphoretic, counterirritant, antiseptic and rubefacient properties.(G4, G7, G64) Traditionally, it has been used for colic, flatulent dyspepsia without inflammation, chronic laryngitis (as a

Cgargle), insufficiency of peripheral circulation and externally for neuralgia including rheumatic pains and unbroken chilblains (as a lotion/ointment). The German Commission E approved external

use for treatment of painful muscle spasms in shoulder, arm and spine; arthritis, rheumatism, lumbago and chilblains.(G3)

Dosage

Dosages for oral administration (adults) for traditional uses recommended in older and contemporary standard herbal reference texts are given below.

Fruit 30–120 mg three times daily.(G7)

Capsicum Tincture (BPC 1968) 0.3–1.0 mL; capsaicin content 0.005–0.01%.(G4)

Stronger Tincture of Capsicum (BPC 1934) 0.06–2.0 mL. Oleoresin 0.6–2.0 mg.(G44)

Oleoresin, internal 1.2 mg (maximum dose), 1.8 mg (maximum daily dose).(G37)

Oleoresin, external 2.5% maximum strength.(G37)

Creams, ointments 0.02–0.05%.(G4)

Pharmacological Actions

Capsaicin has effects on nervous, cardiovascular, respiratory, thermoregulatory and gastrointestinal systems.(1) Capsaicin has

been used as a neurochemical tool for studying sensory neurotransmission.(1)

In vitro and animal studies

Infusion of capsaicin (200 mg/kg, by intravenous injection) has been reported to evoke dose-dependent catecholamine secretion (adrenaline, noradrenaline) from the adrenal medulla of pento- barbitone-anaesthetised rats.(2)

The addition of capsaicin (0.014%) to a high-fat (30%) diet fed to rats was found to reduce serum-triglyceride concentrations but to have no effect on serum cholesterol or pre-b-lipoprotein

Figure 3 Capsicum – dried drug substance (fruit).

concentrations.(3) Capsaicin was thought to stimulate lipid mobilisation from adipose tissue. Lipid absorption was unaffected by capsaicin supplementation.(3)

Activities of two hepatic enzymes, glucose-6-phosphate dehydrogenase and adipose lipoprotein lipase, were elevated in rats when capsaicin was added to the diet.(3) Capsicum extracts fed orally to hamsters have been reported to significantly decrease hepatic vitamin A concentrations.(4) Serum vitamin A concentrations were not affected.(4)

Both the gastric and duodenal mucosae are thought to contain 'capsaicin-sensitive' areas which afford protection against acidand drug-induced ulcers when stimulated by hydrochloric acid or by capsaicin itself. Stimulation causes an increase in mucosal blood flow and/or vascular permeability, inhibits gastric motility, and activates duodenal motility.(5) Desensitisation of these areas, using a regimen involving subcutaneous or oral administration of capsaicin, is thought to remove the protection.(5) However, capsaicin desensitisation was found to have little effect on peripheral responses to stress (i.e. ulcer formation) but did enhance central responses (increase in plasma corticosterone concentration) in rats.(6) The increase in plasma corticosterone

concentration observed in capsaicin-desensitised rats was similar in stressed and non-stressed animals.(6)

Capsaicin was found to influence adrenal cortical activity independently of the presence of a stress factor and may represent a stressor in itself.(6) Capsaicin desensitisation was not found to influence basal gastric acid secretion in non-stressed rats, but did lower pentagastrin-stimulated gastric output.(6) However, other results have reported that capsaicin desensitisation does increase acid secretion.(6)

Capsicum (leaf and stem) has been reported to exhibit uterine stimulant activity in animal studies.(G30)

Pharmacokinetic studies in rats have reported that capsaicin is readily transported via the gastrointestinal tract and absorbed through non-active transport into the portal vein.(2) Capsaicin is partly hydrolysed during absorption and the majority is excreted in the urine within 48 hours.(2, 7) Dihydrocapsaicin-hydrolysing enzyme is present in various organs of the rat but principally in the gastrointestinal tract and the liver. The biotransformation pathway of dihydrocapsaicin in the rat has been studied.(7)

Metabolites are mainly excreted as glucuronide conjugates in the urine.(7)

Clinical studies

Ingestion of red chillies (10 g in wheatmeal) by patients with duodenal ulcers and by control patients does not have a significant effect on acid or pepsin secretion, or on sodium, potassium and chloride concentrations in the gastric aspirate.(8) No apparent change (qualitative or quantitative) in mucous and gastric mucosal erosion was evident.(8) However, in contrast, capsicum has been shown to increase acid concentration and DNA content (indicating exfoliation of epithelial cells) of gastric aspirates in both control subjects and patients with duodenal ulcers.(1) A study involving 18 healthy volunteers suggested that chilli (20 g in 200 mL water) protected against aspirin-induced gastroduodenal mucosal injury, compared with control (water).(9)

Capsicum is applied externally as a counter-irritant in many preparations used for rheumatism, arthritis, neuralgia and lumbago. Clinical studies of topical preparations containing capsaicin have investigated its effectiveness in the treatment of chronic post-herpetic neuralgia, shingles, diabetic neuropathy, rhinopathy and neuropathic pain in cancer patients.(G4) A

systematic review of randomised, double-blind, placebo-con- trolled trials of topical capsaicin included 13 trials involving patients with diabetic neuropathy, osteoarthritis, post-herpetic neuralgia, postmastectomy pain and psoriasis.(10) All the included trials reported that capsaicin was superior to placebo. However, the review drew cautious conclusions because blinding may have been compromised by the irritant effects of capsaicin.

Side-effects, Toxicity

Capsicum contains pungent principles (capsaicinoids) that are strongly irritant to mucosal membranes. Inhalation of paprika can produce a form of allergic alveolitis.(G51)

Chronic administration of capsicum extract (0.5 mg capsaicin/ kg body weight) to hamsters has been reported to be toxic.(4) Treated animals did not survive beyond 17 months whereas all untreated controls survived beyond this period. In addition, eye abnormalities were observed in the treated animals. This effect was attributed to the depletion of substance P in primary afferent neurons by capsaicin, causing a loss of corneal pain sensation and subsequently the loss of protective corneal reflexes.(4)

It is thought that metabolism of capsaicin and related analogues may reduce their acute toxicity.(7) LD50 values stated for capsaicin in mice include 0.56 mg/kg (intravenous), 7.56 mg/kg (intraperitoneal), 9.00 mg/kg (subcutaneous) and 190 mg/kg (oral). In rats, an intraperitoneal LD50 of 10 mg/kg has been reported for capsaicin.(7) The toxicity of capsaicinoids has reportedly not been ascribed to any one specific action but may be due to their causing respiratory failure, bradycardia and hypotension.(7)

Contra-indications, Warnings

Capsicum may cause gastrointestinal irritation, although it has been stated that capsicum does not influence the healing of duodenal ulcers and does not need to be avoided by patients with this condition.(1)

Drug interactions None documented. However, the potential for preparations of capsicum to interact with other medicines administered concurrently, particularly those with similar or opposing effects, should be considered.

There is limited evidence from preclinical studies that capsicum can stimulate catecholamine release and that it can induce activity of glucose-6-phosphate dehydrogenase and adipose lipoprotein lipase in the liver. However, the clinical significance of this, if any (particularly for topical preparations), is not known.

Pregnancy and lactation There are no known problems with the use of capsicum during pregnancy, although it may cause gastrointestinal irritation and should therefore be used with caution. Doses should not greatly exceed amounts normally ingested in foods. It is not known whether the pungent components in capsicum are secreted into breast milk.

Capsicum 127

Preparations

Proprietary single-ingredient preparations

Austria: ABC. Chile: Dolorub Capsico; Parche Leon Fortificante. Germany: Capsamol; Jucurba; Thermo Burger.

C

Proprietary multi-ingredient preparations

Argentina: Sebulex. Australia: Bioglan Joint Mobility; Bioglan The Blue One; Euphrasia Complex; Euphrasia Compound; For Peripheral Circulation Herbal Plus Formula 5; Lifesystem Herbal Formula 6 For Peripheral Circulation; Valerian. Austria: Mentopin; Salhumin; Trauma-Salbe warmend. Belgium: Thermocream. Brazil: Pilulas Ross. Canada: Absorbine Arthritis. Germany: Cremor Capsici compositus; Gothaplast Rheumamed AC. India: Flexi-muv. Israel: Mento-O-Cap. Italy: Gelovis. Malaysia: Dandelion Complex; Total Man. Mexico: Parche Negro Belladona. Netherlands: Cremor capsici comp; Kruidvat Spierbalsem. Portugal: Balsamo Analgesico Sanitas; Medalginan. Russia: Efcamon (Эфкамон); Espol (Эспол). South Africa: Muscle Rub; Tandpyndruppels. Spain: Dolokey; Embrocacion Gras; Linimento Naion. Switzerland: Midalgan. Thailand: Flatulence Gastulence; Meloids. UK: Allens Dry Tickly Cough; Buttercup Syrup; Catarrh Mixture; Hactos; Hansaplast Herbal Heat Plaster; Honey & Molasses; Indian Brandee; Indian Brandee; Indigestion Relief; Jamaican Sarsaparilla; Kilkof; Life Drops; Rheumatic Pain Relief; Sanderson's Throat Specific; Sanderson's Throat Specific; Vegetable Cough Remover. USA: MSM with Glucosamine Creme; Throat Discs. Venezuela: Ehrlich Balsamo.

References

1 Locock RA. Capsicum. Can Pharm J 1985; 118: 517–519.

2Watanabe T et al. Capsaicin, a pungent principle of hot red pepper, evokes catecholamine secretion from the adrenal medulla of

anesthetized rats. Biochem Biophys Res Commun 1987; 142: 259–264.

3Kawada T et al. Effects of capsaicin on lipid metabolism in rats fed a high fat diet. J Nutr 1986; 116: 1272–1278.

4Agrawal RC et al. Chilli extract treatment and induction of eye lesions in hamsters. Toxicol Lett 1985; 28: 1–7.

5Maggi CA et al. Capsaicin-sensitive mechanisms and experimentally induced duodenal ulcers in rats. J Pharm Pharmacol 1987; 39: 559–

561.

6Dugani A, Glavin GB. Capsaicin effects on stress pathology and gastric acid secretion in rats. Life Sci 1986; 39: 1531–1538.

7Kawada T, Iwai K. In vivo and in vitro metabolism of dihydrocapsaicin, a pungent principle of hot pepper in rats. Agric Biol

Chem 1985; 49: 441–448.

8 Pimparkar BND et al. Effects of commonly used spices on human gastric secretion. J Assoc Physicians India 1972: 20: 901–910.

9Yeoh KG et al. Chili protects against aspirin-induced gastroduodenal mucosal injury in humans. Dig Dis Sci 1995; 40: 580–583.

10Zhang WY et al. The effectiveness of topically applied capsaicin. Eur J Clin Pharmacol 1994; 46: 517–522.

C

Summary and Pharmaceutical Comment

The chemistry of cascara is characterised by the anthraquinone derivatives, especially the cascarosides. The laxative action of these compounds is well recognised. Cascara has been used extensively in conventional pharmaceutical preparations. Stimulant laxatives have largely been superseded by bulk-forming laxatives. However, the use of non-standardised anthraquinone-containing preparations should be avoided since their pharmacological effects will be variable and unpredictable. In particular, the use of products containing combinations of anthraquinone laxatives is not advisable.

Species (Family)

Rhamnus purshiana DC. (Frangula purshiana (DC). A. Gray ex J. C. Cooper) (Rhamnaceae)

Synonym(s)

Cascara Sagrada, Rhamni Purshianae Cortex, Rhamnus

Part(s) Used

Bark

Pharmacopoeial and Other Monographs

BHP 1996(G9)

BP 2007(G84)

Complete German Commission E(G3)

ESCOP 2003(G76)

Martindale 35th edition(G85)

Ph Eur 2007(G81)

USP29/NF24(G86)

Legal Category (Licensed Products)

GSL(G37)

Constituents

The following is compiled from several sources, including General References G2, G6, G52, G59 and G62.

Anthracene glycosides Pharmacopoeial standard, not less than 8% hydroxyanthracene glycosides.(G15, G28) Cascarosides A and B are anthrone C- and O-glycosides being 8-O-b-D-glucosides of 10- S-deoxyglucosyl aloe-emodin anthrone (aloin A) and of 10-R- deoxyglucosyl aloe-emodin anthrone (aloin B), respectively. Cascarosides C and D are the 8-O-b-D-glucosides of 10-(R)-(S)- deoxyglucosyl chrysophanol anthrone (chrysaloin A and B, respectively). Cascarosides E and F are the 8-O-b-D-glucosides of 10-deoxyglucosyl emodin-9-anthrone. The cascarosides comprise 60–70% of the total hydroxyanthracene complex. Aloins A and B, chrysaloins A and B account for 10–30% of the total hydroxyanthracene complex. The remaining 10–20% is a mixture of hydroxyanthracene O-glycosides including monoglucosides of aloe-emodin, chrysophanol, emodin and physcion.

Other constituents Linoleic acid, myristic acid, syringic acid, lipids, resin and tannin.

Food Use

Cascara is listed by the Council of Europe as a natural source of food flavouring (category N4). This category indicates that while the use of cascara for flavouring purposes is recognised, it cannot be classified into the categories N1, N2 or N3 because of

insufficient information.(G16) Previously, in the USA, cascara has been approved for food use.(G41)

Herbal Use

Cascara is stated to possess mild purgative properties and has been used for constipation. The German Commission E approved use for treatment of constipation.(G3)

Figure 1 Selected constituents of cascara.

Dosage

Dosages for oral administration (adults) for traditional uses recommended in older and contemporary standard herbal reference texts are given below.

Dried bark 0.3–1 g as a single daily dose.(G3, G76)

Infusion 1.5–2 g of dried bark in 150 mL hot water.(G3, G76)

Cascara Liquid Extract (BP 1980) 2–5 mL.

Preparations Equivalent to 20–30 mg hydroxyanthracene derivatives calculated as cascaroside A, daily.(G3, G76)

Cascara is not recommended for use in children under 10 years of age.(G76)

Pharmacological Actions

The laxative action of anthraquinone glycosides is well recognised (see Senna). Cascara has a laxative action.(G45, G76)

Clinical studies

Studies involving elderly patients suggest that cascara treatment, compared with placebo, leads to relief of constipation and increased bowel movements.(1)

Contra-indications, Warnings