Metabolism capsaicin

Summation The overall response is the arithmetic sum of the contribution brought by each receptor (e.g., NKX and NK2). Capsaicin-induced contraction of rat isolated urinary bladder, electrical field stimulation (EFS)-induced nonadrenergic, noncholinergic contraction of the isolated guinea pig bronchus or renal pelvis when SP metabolism is blocked by peptidase inhibitors are all examples of summation. Both NK and NK2r antagonists are required to abolish such kind of response, but each antagonist substantially reduces the response... 

Surh, Y.J. and Lee, S.S. Capsaicin, a double-edged sword toxicity, metabolism, and chemopreventive potential, Life Sci. 1995, 56, 1845-1855. 

Beyond its role as a painkiller, capsaicin has other benefits. It speeds up metabolism and lowers cholesterol levels, whilst it has antibacterial properties that may protect against peptic ulcers by killing the bacterium Helicobacter pylori which causes them. Chilli pepper s popularity in hot countries may in part be due to its ability to destroy bacteria of the kind that can cause food to go bad and this seems to be borne out by the fact that the countries with the spiciest cuisines are the hottest ones, namely Thailand, the Philippines, India and Malaysia, while those which use the least are the coldest, namely Norway, Sweden and Finland. 

The effect of water stress on phenyl pro-panoid metabolism was studied in Padron pepper plants growing in a greenhouse. The soluble phenolic and lignin contents of fruits from control plants were higher than those of water-stressed plants. The amount of capsaicinoids (capsaicin and dihydrocapsaicin) in the fruits of water-stressed plants was higher than that in control plants (Estrada et al., 1999a). 

Diaz et al. (1998) and Estrada et al. (2000) conducted detailed studies on the biosynthesis of phenolics in capsicum and phenolic metabolism with reference to capsaicin biosynthesis. 

Rizvi and Srivastava (1999) studied the protective effect of capsaicin on the osmotic fragility of human erythrocytes. Capsaicin (from capsicum) exerted a stabilizing effect on human erythrocytes, making them more resistant to lysis under hypotonic stress. The protective effect of capsaicin was due probably to a direct interaction of capsaicin with the erythrocyte membrane rather than due to any alteration in the intracellular metabolism of erythrocytes. 

From a biogenetic standpoint, capsaicin is an acylated degraded phenylpropanoid. Both its aromatic and its acyl moiety are the result of unique metabolic processes that, though simple in principle, are still poorly characterized in terms of enzymology and regulation. Since vanillamine (23) is abundant in placental tissues of Capsicum, the only site of biosynthesis of capsaicinoids, the limiting factor for the synthesis of... 

Capsaicin in humans has a very low oral bioavailability, not because of lack of absorption, but because it is almost completely metabolized in the liver before reaching the general circulation, where it exists almost exclusively as metabolites. The very poor oral bioactivity is also responsible for the large difference in LD50 between oral and dermal administration of capsaicin (LD50 about 190 and >510 mg/kg... 

Capsaicin causes transient bronchoconstriction and induces coughing, especially in individual with severe asthma, potentially triggering fatal crises [37]. These adverse respiratory effects are probably due to the limited capacity of respiratory tissues to metabolize capsaicin (see Section 4.3) [38], and are a major problem with the use of pepper sprays as antiriot agents [37]. Smokers are less sensitive to the respiratory effects of capsaicin, but asthmatic patients should avoid chilies and hot cuisine, as should people using drugs such as ACE-inhibitors, which have an intrinsic capacity to induce cough. 

The uptake, distribution, and metabolism of CS, CR, and capsaicins (but not CN) have been well characterized. 

Capsaicin and capsaicinoids undergo Phase I metabolic bioconversion to catechol metabolites via hydroxylation of the vanillyl ring moiety (Lee and Kumar, 1980 Miller et al, 1983). Metabohsm involves oxidative, in addition to non-oxidative, mechanisms. An example of oxidative conversion involves the liver mixed-function oxidase system to convert capsaicin to an electrophilic epoxide, a reactive metabolite (Olajos, 2004). Surh and Lee (1995) have also demonstrated the formation of a phenoxy radical and quinine product the quinine pathway leads to formation of a highly reactive methyl radical (Reilly et al, 2003). The alkyl side chain of capsaicin also undergoes rapid oxidative deamination (Wehmeyer et al, 1990) or hydroxylation (Surh et al, 1995 Reilly et al, 2003) to hydroxycapsaicin as a detoxification pathway. An example of nonoxidative metabolism of capsaicin is hydrolysis of the acid-amide bond to yield vanillylamide and fatty acyl groups (Kawada et al, 1984 Oi et al, 1992). 

Kawada, T., Suzuki, T., Takahashi, M., Iwai, K. (1984). Gastrointestinal absorption and metabolism of capsaicin and dihydrocapsaicin. Toxicol. Appl. Pharmacol. 72 449-56. 

Reilly, A., Ehlhardt, W.J., Jackson, D.A., Kulanthaivel, P., Mutlib, A.E., Espina, R.J., Moody, D.E., Crouch, D. J., and Yost, G.S., Metabolism of capsaicin by cytochrome P450 produces novel dehydrogenated metabolites and decreases cytotoxicity to the lung and liver cells, Chem. Res. Toxicol., 16, 336-349, 2003. 

The metabolism of capsaicin and dihydrocap-saicin has been studied in the context of food and their use in skin creams for the treatment of arthritic pain and inflammation. Capsaicin (Figure 17) is a much more complex molecule than other RCAs, and offers more functional groups and other sites for metabolism, cu-Hydroxycapsaicin (28) was detected in the urine... 

Detailed metabolism studies have been reported for the RCAs, CS and CR, and to a lesser extent, capsaicin, but sensitive analytical methods for the metabolites have yet to be developed. The formation of covalent adducts with proteins has been little studied, although observations have suggested that CS and CN react with proteins. In the case of CS and capsaicin, major metabolites are derived from an initial hydrolysis with loss of some of the carbon skeleton, and it needs to be established if background levels of these metabolites occur in non-exposed individuals. 

Reilly CA, Ehlhardt WJ, Jackson DA el al. (2003). Metabolism of capsaicin by cytochrome P450 produces novel dehydrogenated metabolites and decreases cytotoxicity to lung and liver cells. Chem Res Toxicol, 16, 336-349. 

Capsaicin and capsaicinoids may be involved in complex interactions in vivo related to carcinogenesis, cocarcinogenesis and anticarcinogenesis, which are a reflection, in part, of metabolism and metabolite activity. Capsaicin... 

Lee SS and Kumar S (1980). Metabolism in vitro of capsaicin, a pungent principle of red pepper, with rat liver homogenates. In Microsomes, Drug Oxidation, and Chemical Carcinogenesis, Volume 2. (MJ Coon, AH Conney, RW Estabrook, eds), pp. 1009-1012. New York, NY, USA Academic Press. 

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