AN OVERVIEW ABOUT VERSATILE MOLECULE CAPSAICIN
Abstract
Capsaicin is a pungent highly domesticated fat soluble alkaloid having its origin from Bolvia and Brazil. It is biosynthesized via phenylpropanoid pathway and branched chain fatty acid pathway. Mostly found in trans isomeric form. Its pungent analogues are synthesized using amidation reactions catalyzed by lipases and non-pungent analogues using acyl chain lengths and different substituent in aromatic ring. It acts by binding TRPV1 and shows wide applications in relief from pain, breast and prostate cancer, obesity, heart diseases and hair loses. Its increased intake may cause lesions of liver and kidney along with gastric cancer. A review is made of capsaicin research focusing mainly on its origin, biosynthesis, chemistry and pharmacology, including its toxicological aspects.
Keywords:
Capsaicin, origin, biosynthesis, chemistry, pharmacology.DOI
https://doi.org/10.25004/IJPSDR.2011.030402References
1. Lee J, Li Y, Li C, Li D. Natural products and body weight control. North Am J Med Sci. 2011; 3: 13-19.
2. Hiroki H, Shogo O, Tomohisa N, Hisashi K, Takeshi T, Hatsuyuki H, Nobuyoshi N, Kohji I. One-step Glucosylation of Capsaicinoids by Cultured Cells of Phytolacca americana. Plant Biotech. 2003; 20: 253-255.
3. Committee of Experts on Flavouring Substances (2005). Active principles (constituents of toxicological concern) contained in natural sources of flavourings. (Cited on 2011, May 18). Available from URL: http://www.coe.int/t/e/social_cohesion/socsp/public_health/flavouring_substances/Active%20principles.pdf.
4. Toh CC, Lee TS, Kiang AK. The pharmacological actions of capsaicin and analogues. Brit. J. Pharmacol. 1955; 10: 175.
5. Kumar R, Dwivedi N, Singh RK, Kumar S, Rai VP, Singh M. A review on molecular characterization of pepper for capsaicin and oleoresin. Int. J. Plant Breed. Genet. 2011; 5: 99-110.
6. Nunn N, Qian N. The Columbian Exchange: A History of Disease, Food, and Ideas. J. Econ. Pers. 2010; 24: 163-188.
7. Prasad BCN, Kumar V, Gururaj HB, Parimalan R, Giridhar P, Ravishankar GA. Characterization of capsaicin synthase and identification of its gene (csy1) for pungency factor capsaicin in pepper (Capsicum sp.). Proc. Natl. Acad. Sci. USA. 2006; 103: 13315–13320.
8. Kang BC, Nahm SH, Huh JH, Yoo HS, Yu JW, Lee MH, Kim BD. An interspecific (Capsicum annuum× C. chinese) F2 linkage map in pepper using RFLP and AFLP markers. Theor. Appl. Genet. 2001; 102: 531–539.
9. Goodwin DC, Hertwig M. Peroxidase-catalyzed oxidation of capsaicinoids: steady-state and transient-state kinetic studies. Arch. Biochem. Biophys. 2003; 417: 18–26.
10. Eshbaugh WH. The taxonomy of the genus Capsicum (Solanaceae) – 1980. Phytologia, 1980; 47: 153-166.
11. Hunziker AT. The Biology and Taxonomy of the Solanaceae. Linnean Society Symposium Series No. 7, Academic Press, London and New York, 1979, pp. 49-85.
12. Walsh BM, Hoot SB. Phylogenetic relationships of Capsicum (Solanaceae) using DNA sequences from two noncoding regions: the chloroplast atpB‐rbcL spacer region and nuclear waxy Introns. Int. J. Plant Sci. 2001; 162: 1409–1418.
13. Gonzalez M, Bosland P. Strategies for stemming genetic erosion of Capsicum germplasm in the Americas. Diversity. 1991; 7: 52-53.
14. WWF and IUCN. Centres of Plant Diversity: Vol. 3. The Americas, Cambridge, England, UK, IUCN Publications Unit, 1997, pp. 562.
15. Andrews J. Peppers: The Domesticated Capsicums, University of Texas Press, Austin, Texas, 1995.
16. Yao J. An investigation of capsaicinoids and bioactive compounds in 'Scotch Bonnet' and several other cultivars of pepper, M. S. thesis, Michigan State University, Michigan, 1992.
17. Cheema SK, Pant MR. Estimation of capsaicin in seven cultivated varieties of Capsicum Annuum L. Res J Pharm Biol Chem Sci. 2011; 2: 701-706.
18. Supalkova V, Stavelikova H, Krizkova S, Adam V, Horna A, Havel L, Ryant P, Babula P, Kizek R. Study of capsaicin content in various parts of pepper fruit by liquid chromatography with electrochemical detection. Acta Chim Slov. 2007; 54: 55-59.
19. Bosland PW. Innovative uses of an ancient crop. ASHS Press, Arlington, VA, 1996, pp. 479-487.
20. Andrews J. Peppers: The Domesticated Capsicums, University of Texas Press, Austin, Texas, 1984.
21. Purseglove JW, Brown EG, Green CL, Robbins SRJ. Spices, Longman Publishers, London, 1981.
22. Conway SJ. TRPing the switch on pain: an introduction to the chemistry and biology of capsaicin and TRPV1. Chem. Soc. Rev. 2008; 37: 1530-1545.
23. Capsaicin @ 3dchem.com. (Cited on 2011, May 22). Available from URL: http://www.3dchem.com/molecules.asp?ID=105.
24. Katritzky AR, Xu YJ, Vakulenko AV, Wilcox AL, Bley KR. Model compounds of caged capsaicin: design, synthesis, and photoreactivity. J. Org. Chem. 2003; 68: 9100-9104.
25. Walpole CS, Bevan S, Bloomfield G, Breckenridge R, James IF, Ritchie T, Szallasi A, Winter J, Wrigglesworth R. Similarities and differences in the structure-activity relationships of capsaicin and resiniferatoxin analogues. J. Med. Chem. 1996; 39: 2939-2952.
26. Barbero GF, Molinillo JMG, Varela RM, Palma M, Macias FA, Barroso CG. Application of Hansch´s model to capsaicinoids and capsinoids: a study using the quantitative structure-activity relationship. A novel method for the synthesis of capsinoids. J. Agric. Food Chem. 2010; 58: 3342-3349.
27. Harvell KP, Bosland PW. The environment produces a significant effect on pungency of chiles. Hort. Sci. 1998; 32: 1292.
28. Blum E, Mazourek M, O'Connell M, Curry J, Thorup T, Liu K, Jahn M, Paran I. Molecular mapping of capsaicinoid biosynthesis genes and quantitative trait loci analysis for capsaicinoid content in Capsicum. Theor. Appl. Genet. 2003; 108: 79-86.
29. Curry J, Aluru M, Mendoza M, Nevarez J, Melendrez M, O'Connell MA. Transcripts for possible capsaicinoid biosynthetic genes are differentially accumulated in pungent and nonpungent Capsicum spp. Plant Sci. 1999; 148: 47-57.
30. Aluru MR, Mazourek M, Landry LG, Curry J, Jahn M, O´Conell MA. Aluru MR, Mazourek M, Landry LG, Curry J, Jahn M, O´Conell MA. J. Exp. Bot. 2003; 54: 1655-1664.
31. Stewart C, Kang BC, Liu K, Mazourek M, Moore SL, Yoo EY, Kim BD, Paran I, Jahn MM. The pun1 gene for pungency in pepper encodes a putative acyltransferase. Plant J. 2005; 42: 675-688.
32. Stewart C, Mazourek M, Stellari GM, O'Connell M, Jahn M. Genetic control of pungency in C. chinense via the Pun1 locus. J. Exp. Bot. 2007; 58: 979-991.
33. Bennett DJ, Kirby GW. Constitution and biosynthesis of capsaicin. J. Chem. Soc. C. 1968; 442–446.
34. Leete E, Louden M. Biosynthesis of capsaicin and dihydrocapsaicin in Capsicum frutescens. J. Amer. Chem. Soc. 1968; 90: 6837–6841.
35. Sukrasno N, Yeoman MM. Phenylpropanoid metabolism during growth and development of Capsicum frutescens fruits. Phytochemistry. 1993; 32: 839–844.
36. Fujiwake H, Suzuki T, Iwai K. Intracellular distributions of enzymes and intermediates involved in biosynthesis of capsaicin and its analogues in Capsicum fruits. Agric. Biol. Chem. 1982; 46: 2685–2689.
37. Sung Y, Chang YY, Ting NL. Capsaicin biosynthesis in water-stressed hot pepper fruits. Bot. Bull. Acad. Sin. 2005; 46: 35-42.
38. Ochoa-Alejo N, Gomez-Peralta JE. Activity of enzymes involved in capsaicin biosynthesis in callus tissue and fruits of chili pepper (Capsicum annuum L.). J. Plant Physiol. 1993; 141: 147–152.
39. González Molinillo JM, Macias Domínguez FA, Varela Montoya RM, Palma Lovillo M, García Barroso C, Fernández Barbero G. Method for the chemical synthesis of capsinoids. US Pat.No. 0256413 A1, 2010.
40. Iwai K, Watanabe T, Tamura Y, Ogawa S. Method of producing capsaicin analogues. US Pat.No. 6,022,718, 2000.
41. Kobata K, Kobayashi M, Tamura Y, Miyoshi S, Ogawa S, Watanabe T. Lipase-catalyzed synthesis of capsaicin analogs by transacylation of capsaicin with natural oils or fatty acid derivatives in n-hexane. Biotechnol. Lett. 1999; 21: 547-550.
42. Kobata K, Toyoshima M, Kawamura M, Watanabe T. Lipase-catalyzed synthesis of capsaicin analogs using natural oils as an acyl donor. Biotechnol. Lett. 1998; 20: 781-783.
43. Castillo E, Lopez-Gonzalez I, De Regil-Hernandez R, Reyes-Duarte D, Sánchez-Herrera D, López-Munguía A, Darszon A. Enzymatic synthesis of capsaicin analogs and their effect on the T-type Ca2+ channels. Biochem. Biophys. Res. Comm. 2007; 356: 424-430.
44. Castillo E, Torres-Gavilán A, Severiano P, Arturo N, López-Munguía A. Lipase-catalyzed synthesis of pungent capsaicin analogues. Food Chem. 2007; 100: 1202-1208.
45. Kaga H, Goto K, Takahashi T, Hino M, Tokuhashi T, Orito K. A general and stereoselective synthesis of the capsaicinoids via the orthoester Claisen rearrangement. Tetrahedron. 1996; 52: 8451-8470.
46. Choi HY, Yoon SH. Synthesis of 1-hydroxy-2-pyridone analogue. Bull. Kor. Chem. Soc. 1999; 20: 857-859.
47. Appendino G, Minassi A, Morello AS, De Petrocellis L, Di Marzo V. Development of an expeditious synthesis and discovery of new acyl templates for powerful activation of the vanilloid receptor. J. Med. Chem. 2002; 45: 3739-3745.
48. Torregiani E, Seu G, Minassi A, Appendino G. Cerium (III) chloride promoted chemoselective esterification of phenolic alcohols. Tetrahedron Lett. 2005; 46: 2193-2196.
49. Amino Y, Kurosawa W, Nakano T, Hirasawa K. Production method of capsinoid by dehydratation condensation, stabilizing method of capsinoid, and capsinoid composition. US Pat.No. 7700331, 2010.
50. Barbero GF, Molinillo JMG, Varela RM, Palma M, Macias FA, Barroso CG. Application of Hansch´s model to capsaicinoids and capsinoids: a study using the quantitative structure-activity relationship. A novel method for the synthesis of capsinoids. J. Agric. Food Chem. 2010; 58: 3342-3349.
51. Rao SR, Ravishankar GA. Plant cell cultures: Chemical factories of secondary metabolites. Biotechnology Advances. 2002; 20: 101-153.
52. Nuñez-Palenius H, Ochoa-Alejo N. Effect of phenylalanine and phenylpropanoids on the accumulation of capsaicinoids and lignin in cell cultures of chili pepper (Capsicum annuum L.). In Vitro Cell. Dev. Biol. Plant. 2005; 41: 801-805.
53. Pandhair V, Gosal SS. Capsaicin production in cell suspension cultures derived from placenta of Capsicum annuum L. fruit. Indian J. Agric. Biochem. 2009; 22: 78-82.
54. Veeresham C, Kokate CK, Apte SS, Venkateshwarlu V. Effect of precursors on capsaicin Synthesis in Suspension Cultures of Capsicum annuum. Plant Tiss. Cult. 1993; 3: 67-70.
55. Lindsey K. Incorporation of [14C] phenylalanine and [14C] cinnamic acid into capsaicin in cultured cells of Capsicum frutescens. Phytochemistry. 1986; 25: 2793-2801.
56. Johnson TS, Ravishankar GA, Venkataraman LV. In vitro capsaicin production by immobilized cells and placental tissues of Capsicum annuum L. grown in liquid medium. Plant Sci. 1990; 70: 223-229.
57. Pershing LK, Reilly CA, Corlett JL, Crouch DJ. Effects of vehicle on the uptake and elimination kinetics of capsaicinoids in human skin in vivo. Toxicol. Appl. Pharmacol. 2004; 200: 73-81.
58. Suresh D, Srinivasan K. Tissue distribution and elimination of capsaicin, piperine and curcumin following oral intake in rats. Indian J. Med. Res. 2010; 131: 682-691.
59. Chanda S, Bashir M, Babbar S, Koganti A, Bley K. In vitro hepatic and skin metabolism of capsaicin. Drug Metab. Dispos. 2008; 36: 670-675.
60. Kawada 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.
61. Cortright DN, Szallasi A. Biochemical pharmacology of the vanilloid receptor TRPV1. Eur. J. Biochem. 2004; 271: 1814-1819.
62. Tominaga M, Tominaga T. Structure and function of TRPV1. Pflugers Arch. 2005; 451: 143-150.
63. Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D. Nature. 1997; 389: 816-824.
64. Liu M, Liu MC, Magoulas C, Priestley JV, Willmott NJ. Versatile regulation of cytosolic Ca2+ by vanilloid receptor I in rat dorsal root ganglion neurons. J. Biol. Chem. 2003; 278: 5462-5472.
65. Kárai LJ, Russell JT, Iadarola MJ, Oláh Z. Vanilloid receptor 1 regulates multiple calcium compartments and contributes to Ca2+ induced Ca2+ release in sensory neurons. J. Biol. Chem. 2004; 279: 16377-16387.
66. Morita A, Iwasaki Y, Kobata K, Lida T, Higashi T, Oda K, Susuki A, Narukawa M, Sasakuma S, Yokogoshi H, Yazawa S, Tominaga M, Watanabe T. Lipophilicity of capsaicinoids and capsinoids influences the multiple activation process of rat TRPV1. Life Sci. 2006; 79: 2303-2310.
67. Pingle SC, Matta JA, Ahern GP. TRPV1 a promiscuous TRP channel. Handb. Exp. Pharmacol. 2007; 179: 155-171.
68. Bevan S, Szolcsanyi J. Sensory neuron-specific actions of capsaicin: mechanisms and applications. Trends Pharmacol. Sci. 1990; 11: 330-333.
69. Saria A, Lundberg JM, Hua X, Lembeck F. Capsaicin-induced substance P release and sensory control of vascular permeability in the guinea-pig ureter. Neurosci. Lett. 1983; 41: 167-172.
70. Jhamandas K, Yaksh TL, Harty G, Szolcsanyi J, Go VL. Action of intrathecal capsaicin and its structural analogues on the content and release of spinal substance P: selectivity of action and relationship to analgesia. Brain Res. 1984; 306: 215-225.
71. Purkiss J, Welch M, Doward S, Foster K. Capsaicin-stimulated release of substance P from cultured dorsal root ganglion neurons: involvement of two distinct mechanisms. Biochem. Pharmacol. 2000; 59: 1403-1406.
72. Szolcsanyi J, Oroszi G, Nemeth J, Szilvassy Z, Tosaki A. Endothelin release by capsaicin in isolated working rat heart. Eur. J. Pharmacol. 1999; 376: 247-250.
73. Dutta A, Deshpande SB. Mechanisms underlying the hypertensive response induced by capsaicin. Int. J. Cardiol. 2010; 145: 358-359.
74. Fraenkel L, Jr Bogardus ST, Concato J, Wittink DR. Treatment options in knee osteoarthritis: the patient's perspective. Arch. Intern. Med. 2004; 164: 1299–1304.
75. Remadevi R, Szallisi A. Adlea (ALGRX-4975), an injectable capsaicin (TRPV1 receptor agonist) formulation for longlasting pain relief. IDrugs. 2008; 11: 120–132.
76. Knotkova H, Pappagallo M, Szallasi A. Capsaicin (TRPV1 agonist) therapy for pain relief: farewell or revival. Clin. J. Pain. 2008; 24: 142–154.
77. Surh YJ. More than spice: capsaicin in hot chili peppers makes tumor cells commit suicide. J. Natl Cancer Inst. 2002; 94: 1263–1265.
78. Oh SH, Kim YS, Lim SC, Hou YF, Chang IY, You HJ. Dihydrocapsaicin (DHC), a saturated structural analog of capsaicin, induces autophagy in human cancer cells in a catalase-regulated manner. Autophagy. 2008; 4: 1009–1019.
79. Thoennissen NH, O'Kelly J, Lu D, Iwanski GB, La DT, Abbassi S, Leiter A, Karlan B, Mehta R, Koeffler HP. Capsaicin causes cell-cycle arrest and apoptosis in ER-positive and -negative breast cancer cells by modulating the EGFR/HER-2 pathway. Oncogene. 2010; 29: 285–296.
80. Yang ZH, Wang XH, Wang HP, Hu LQ, Zheng XM, Li SW. Capsaicin mediates cell death in bladder cancer T24 cells through reactive oxygen species production and mitochondrial depolarization. Urology. 2010; 75: 735–741.
81. Ito K, Nakazato T, Yamato K, Miyakawa Y, Yamada T, Hozumi N, Segawa K, IkedaY, Kizaki M. Induction of apoptosis in leukemic cells by homovanillic acid derivative, capsaicin, through oxidative stress: implication of phosphorylation of p53 at Ser-15 residue by reactive oxygen species. Cancer Res. 2004; 64: 1071–1078.
82. Choi CH, Jung YK, Oh SH. Selective induction of catalase-mediated autophagy by dihydrocapsaicin in lung cell lines. Free Radic. Biol. Med. 2010; 49: 245–257.
83. Ghosh AK, Basu S. Fas-associated factor 1 is a negative regulator in capsaicin induced cancer cell apoptosis. Cancer Lett. 2010; 287: 142–149.
84. Oh S, Choi CH, Jung YK. ) Autophagy induction by capsaicin in malignant human breast cells is modulated by p38 and ERK mitogen-activated protein kinase and retards cell death by suppressing endoplasmic reticulum stress-mediated apoptosis. Mol. Pharmacol. 2010; 78: 114–125.
85. Zhang J, Nagasaki M, Tanaka Y, Morikawa S. Capsaicin inhibits growth of adult T-cell leukemia cells. Leuk. Res. 2003; 27: 275–283.
86. Singh S, Asad SF, Ahmad A, Khan NU, Hadi SM. Oxidative DNA damage by capsaicin and dihydrocapsaicin in the presence of Cu(II). Cancer Lett. 2001; 169: 139–146.
87. Kim S, Moon A. Capsaicin-induced apoptosis of H-ras-transformed human breast epithelial cells is Rac-dependent via ROS generation. Arch. Pharm. Res. 2004; 27: 845–849.
88. Baez S, Tsuchiya Y, Calvo A, Pruyas M, Nakamura K, Kiyohara C, Oyama M, Yamamoto M. Yamamoto M. Genetic variants involved in gallstone formation and capsaicin metabolism, and the risk of gallbladder cancer in Chilean women. World J. Gastroenterol. 2010; 16: 372–378.
89. Cui J, Himms-Hagen J. Long-term decrease in body fat and in brown adipose tissue in capsaicin-desensitized rats. Am. J. Physiol. 1992; 262: R568–R573.
90. Joo JI, Kim DH, Choi JW, Yun JW. Proteomic analysis for antiobesity potential of capsaicin on white adipose tissue in rats fed with a high fat diet. J. Proteome Res. 2010; 9: 2977–2987.
91. Leung FW. Capsaicin-sensitive intestinal mucosal afferent mechanism and body fat distribution. Life Sci. 2008; 83: 1–5.
92. Reinbach HC, Smeets A, Martinussen T, Moller P, Westerterp-Plantenga MS. Effects of capsaicin, green tea and CH-19 sweet pepper on appetite and energy intake in humans in negative and positive energy balance. Clin. Nutr. 2009; 28: 260–265.
93. Shin KO, Moritani TJ. Alterations of autonomic nervous activity and energy metabolism by capsaicin ingestion during aerobic exercise in healthy men. J. Nutr. Sci. Vitaminol. Tokyo. 2007; 53: 124–132.
94. Harada N, Okajima K. Effects of capsaicin and isoflavone on blood pressure and serum levels of insulin-like growth factor-I in normotensive and hypertensive volunteers with alopecia. Biosci. Biotechnol. Biochem. 2009; 73: 1456–1459.
95. Peng J, Li YJ. The vanilloid receptor TRPV1: role in cardiovascular and gastrointestinal protection. Eur. J. Pharmacol. 2010; 627: 1–7.
96. Zvara A, Bencsik P, Fodor G, Csont T, Jr Hackler L, Dux M, Furst S, Jancso G, Puskas LG, Ferdinandy P. Capsaicin-sensitive sensory neurons regulate myocardial function and gene expression pattern of rat hearts: a DNA microarray study. FASEB J. 2006; 20: 160–162.
97. Zhou Z, Peng J, Wang CJ, Li D, Li TT, Hu CP, Chen XP, Li YJ. Accelerated senescence of endothelial progenitor cells in hypertension is related to the reduction of calcitonin gene-related peptide. J. Hypertens. 2010; 28: 931–939.
98. Adams MJ, Ahuja KD, Geraghty DP. Effect of capsaicin and dihydrocapsaicin on in vitro blood coagulation and platelet aggregation. Thromb. Res. 2009; 124: 721–723.
99. Hogaboam CM, Wallace JL. Inhibition of platelet aggregation by capsaicin. An effect unrelated to actions on sensory afferent neurons. Eur. J. Pharmacol. 1991; 202: 129–131.
100. Harper AG, Brownlow SL, Sage SO. A role for TRPV1 in agonist-evoked activation of human platelets. J. Thromb. Haemost. 2009; 7: 330–338.
101. Ahuja KD, Ball MJ. Effects of daily ingestion of chilli on serum lipoprotein oxidation in adult men and women. Br. J. Nutr. 2006; 96: 239–242.
102. Wang L, Hu CP, Deng PY, Shen SS, Zhu HQ, Ding JS, Tan GS Li YJ. The protective effects of rutaecarpine on gastric mucosa injury in rats. Planta Med. 2005; 71: 416–419.
103. Nishihara K, Nozawa Y, Nakano M, Ajioka H, Matsuura N. Sensitizing effects of lafutidine on CGRP-containing afferent nerves in the rat stomach. Br. J. Pharmacol. 2002; 135: 1487–1494.
104. Serra MPM, Llorca CS, Donat FJS. Pharmacological treatment of burning mouth syndrome: A review and update. Med Oral Patol Oral Cir Bucal. 2007; 12; E299-304.
105. Naoaki AH, Kenji AO, Masatoku AA, Hiroki BK, Naomi N. Administration of capsaicin and isoflavone promotes hair growth by increasing insulin-like growth factor-I production in mice and in humans with alopecia. Growth Hormone & IGF Research. 2007; 17: 408–415.
106. Surh YJ, Lee SS. Capsaicin, a double-edged sword: Toxicity, metabolism, and chemopreventive potential. Life Sciences. 1995; 56: 1845-1855.
2. Hiroki H, Shogo O, Tomohisa N, Hisashi K, Takeshi T, Hatsuyuki H, Nobuyoshi N, Kohji I. One-step Glucosylation of Capsaicinoids by Cultured Cells of Phytolacca americana. Plant Biotech. 2003; 20: 253-255.
3. Committee of Experts on Flavouring Substances (2005). Active principles (constituents of toxicological concern) contained in natural sources of flavourings. (Cited on 2011, May 18). Available from URL: http://www.coe.int/t/e/social_cohesion/socsp/public_health/flavouring_substances/Active%20principles.pdf.
4. Toh CC, Lee TS, Kiang AK. The pharmacological actions of capsaicin and analogues. Brit. J. Pharmacol. 1955; 10: 175.
5. Kumar R, Dwivedi N, Singh RK, Kumar S, Rai VP, Singh M. A review on molecular characterization of pepper for capsaicin and oleoresin. Int. J. Plant Breed. Genet. 2011; 5: 99-110.
6. Nunn N, Qian N. The Columbian Exchange: A History of Disease, Food, and Ideas. J. Econ. Pers. 2010; 24: 163-188.
7. Prasad BCN, Kumar V, Gururaj HB, Parimalan R, Giridhar P, Ravishankar GA. Characterization of capsaicin synthase and identification of its gene (csy1) for pungency factor capsaicin in pepper (Capsicum sp.). Proc. Natl. Acad. Sci. USA. 2006; 103: 13315–13320.
8. Kang BC, Nahm SH, Huh JH, Yoo HS, Yu JW, Lee MH, Kim BD. An interspecific (Capsicum annuum× C. chinese) F2 linkage map in pepper using RFLP and AFLP markers. Theor. Appl. Genet. 2001; 102: 531–539.
9. Goodwin DC, Hertwig M. Peroxidase-catalyzed oxidation of capsaicinoids: steady-state and transient-state kinetic studies. Arch. Biochem. Biophys. 2003; 417: 18–26.
10. Eshbaugh WH. The taxonomy of the genus Capsicum (Solanaceae) – 1980. Phytologia, 1980; 47: 153-166.
11. Hunziker AT. The Biology and Taxonomy of the Solanaceae. Linnean Society Symposium Series No. 7, Academic Press, London and New York, 1979, pp. 49-85.
12. Walsh BM, Hoot SB. Phylogenetic relationships of Capsicum (Solanaceae) using DNA sequences from two noncoding regions: the chloroplast atpB‐rbcL spacer region and nuclear waxy Introns. Int. J. Plant Sci. 2001; 162: 1409–1418.
13. Gonzalez M, Bosland P. Strategies for stemming genetic erosion of Capsicum germplasm in the Americas. Diversity. 1991; 7: 52-53.
14. WWF and IUCN. Centres of Plant Diversity: Vol. 3. The Americas, Cambridge, England, UK, IUCN Publications Unit, 1997, pp. 562.
15. Andrews J. Peppers: The Domesticated Capsicums, University of Texas Press, Austin, Texas, 1995.
16. Yao J. An investigation of capsaicinoids and bioactive compounds in 'Scotch Bonnet' and several other cultivars of pepper, M. S. thesis, Michigan State University, Michigan, 1992.
17. Cheema SK, Pant MR. Estimation of capsaicin in seven cultivated varieties of Capsicum Annuum L. Res J Pharm Biol Chem Sci. 2011; 2: 701-706.
18. Supalkova V, Stavelikova H, Krizkova S, Adam V, Horna A, Havel L, Ryant P, Babula P, Kizek R. Study of capsaicin content in various parts of pepper fruit by liquid chromatography with electrochemical detection. Acta Chim Slov. 2007; 54: 55-59.
19. Bosland PW. Innovative uses of an ancient crop. ASHS Press, Arlington, VA, 1996, pp. 479-487.
20. Andrews J. Peppers: The Domesticated Capsicums, University of Texas Press, Austin, Texas, 1984.
21. Purseglove JW, Brown EG, Green CL, Robbins SRJ. Spices, Longman Publishers, London, 1981.
22. Conway SJ. TRPing the switch on pain: an introduction to the chemistry and biology of capsaicin and TRPV1. Chem. Soc. Rev. 2008; 37: 1530-1545.
23. Capsaicin @ 3dchem.com. (Cited on 2011, May 22). Available from URL: http://www.3dchem.com/molecules.asp?ID=105.
24. Katritzky AR, Xu YJ, Vakulenko AV, Wilcox AL, Bley KR. Model compounds of caged capsaicin: design, synthesis, and photoreactivity. J. Org. Chem. 2003; 68: 9100-9104.
25. Walpole CS, Bevan S, Bloomfield G, Breckenridge R, James IF, Ritchie T, Szallasi A, Winter J, Wrigglesworth R. Similarities and differences in the structure-activity relationships of capsaicin and resiniferatoxin analogues. J. Med. Chem. 1996; 39: 2939-2952.
26. Barbero GF, Molinillo JMG, Varela RM, Palma M, Macias FA, Barroso CG. Application of Hansch´s model to capsaicinoids and capsinoids: a study using the quantitative structure-activity relationship. A novel method for the synthesis of capsinoids. J. Agric. Food Chem. 2010; 58: 3342-3349.
27. Harvell KP, Bosland PW. The environment produces a significant effect on pungency of chiles. Hort. Sci. 1998; 32: 1292.
28. Blum E, Mazourek M, O'Connell M, Curry J, Thorup T, Liu K, Jahn M, Paran I. Molecular mapping of capsaicinoid biosynthesis genes and quantitative trait loci analysis for capsaicinoid content in Capsicum. Theor. Appl. Genet. 2003; 108: 79-86.
29. Curry J, Aluru M, Mendoza M, Nevarez J, Melendrez M, O'Connell MA. Transcripts for possible capsaicinoid biosynthetic genes are differentially accumulated in pungent and nonpungent Capsicum spp. Plant Sci. 1999; 148: 47-57.
30. Aluru MR, Mazourek M, Landry LG, Curry J, Jahn M, O´Conell MA. Aluru MR, Mazourek M, Landry LG, Curry J, Jahn M, O´Conell MA. J. Exp. Bot. 2003; 54: 1655-1664.
31. Stewart C, Kang BC, Liu K, Mazourek M, Moore SL, Yoo EY, Kim BD, Paran I, Jahn MM. The pun1 gene for pungency in pepper encodes a putative acyltransferase. Plant J. 2005; 42: 675-688.
32. Stewart C, Mazourek M, Stellari GM, O'Connell M, Jahn M. Genetic control of pungency in C. chinense via the Pun1 locus. J. Exp. Bot. 2007; 58: 979-991.
33. Bennett DJ, Kirby GW. Constitution and biosynthesis of capsaicin. J. Chem. Soc. C. 1968; 442–446.
34. Leete E, Louden M. Biosynthesis of capsaicin and dihydrocapsaicin in Capsicum frutescens. J. Amer. Chem. Soc. 1968; 90: 6837–6841.
35. Sukrasno N, Yeoman MM. Phenylpropanoid metabolism during growth and development of Capsicum frutescens fruits. Phytochemistry. 1993; 32: 839–844.
36. Fujiwake H, Suzuki T, Iwai K. Intracellular distributions of enzymes and intermediates involved in biosynthesis of capsaicin and its analogues in Capsicum fruits. Agric. Biol. Chem. 1982; 46: 2685–2689.
37. Sung Y, Chang YY, Ting NL. Capsaicin biosynthesis in water-stressed hot pepper fruits. Bot. Bull. Acad. Sin. 2005; 46: 35-42.
38. Ochoa-Alejo N, Gomez-Peralta JE. Activity of enzymes involved in capsaicin biosynthesis in callus tissue and fruits of chili pepper (Capsicum annuum L.). J. Plant Physiol. 1993; 141: 147–152.
39. González Molinillo JM, Macias Domínguez FA, Varela Montoya RM, Palma Lovillo M, García Barroso C, Fernández Barbero G. Method for the chemical synthesis of capsinoids. US Pat.No. 0256413 A1, 2010.
40. Iwai K, Watanabe T, Tamura Y, Ogawa S. Method of producing capsaicin analogues. US Pat.No. 6,022,718, 2000.
41. Kobata K, Kobayashi M, Tamura Y, Miyoshi S, Ogawa S, Watanabe T. Lipase-catalyzed synthesis of capsaicin analogs by transacylation of capsaicin with natural oils or fatty acid derivatives in n-hexane. Biotechnol. Lett. 1999; 21: 547-550.
42. Kobata K, Toyoshima M, Kawamura M, Watanabe T. Lipase-catalyzed synthesis of capsaicin analogs using natural oils as an acyl donor. Biotechnol. Lett. 1998; 20: 781-783.
43. Castillo E, Lopez-Gonzalez I, De Regil-Hernandez R, Reyes-Duarte D, Sánchez-Herrera D, López-Munguía A, Darszon A. Enzymatic synthesis of capsaicin analogs and their effect on the T-type Ca2+ channels. Biochem. Biophys. Res. Comm. 2007; 356: 424-430.
44. Castillo E, Torres-Gavilán A, Severiano P, Arturo N, López-Munguía A. Lipase-catalyzed synthesis of pungent capsaicin analogues. Food Chem. 2007; 100: 1202-1208.
45. Kaga H, Goto K, Takahashi T, Hino M, Tokuhashi T, Orito K. A general and stereoselective synthesis of the capsaicinoids via the orthoester Claisen rearrangement. Tetrahedron. 1996; 52: 8451-8470.
46. Choi HY, Yoon SH. Synthesis of 1-hydroxy-2-pyridone analogue. Bull. Kor. Chem. Soc. 1999; 20: 857-859.
47. Appendino G, Minassi A, Morello AS, De Petrocellis L, Di Marzo V. Development of an expeditious synthesis and discovery of new acyl templates for powerful activation of the vanilloid receptor. J. Med. Chem. 2002; 45: 3739-3745.
48. Torregiani E, Seu G, Minassi A, Appendino G. Cerium (III) chloride promoted chemoselective esterification of phenolic alcohols. Tetrahedron Lett. 2005; 46: 2193-2196.
49. Amino Y, Kurosawa W, Nakano T, Hirasawa K. Production method of capsinoid by dehydratation condensation, stabilizing method of capsinoid, and capsinoid composition. US Pat.No. 7700331, 2010.
50. Barbero GF, Molinillo JMG, Varela RM, Palma M, Macias FA, Barroso CG. Application of Hansch´s model to capsaicinoids and capsinoids: a study using the quantitative structure-activity relationship. A novel method for the synthesis of capsinoids. J. Agric. Food Chem. 2010; 58: 3342-3349.
51. Rao SR, Ravishankar GA. Plant cell cultures: Chemical factories of secondary metabolites. Biotechnology Advances. 2002; 20: 101-153.
52. Nuñez-Palenius H, Ochoa-Alejo N. Effect of phenylalanine and phenylpropanoids on the accumulation of capsaicinoids and lignin in cell cultures of chili pepper (Capsicum annuum L.). In Vitro Cell. Dev. Biol. Plant. 2005; 41: 801-805.
53. Pandhair V, Gosal SS. Capsaicin production in cell suspension cultures derived from placenta of Capsicum annuum L. fruit. Indian J. Agric. Biochem. 2009; 22: 78-82.
54. Veeresham C, Kokate CK, Apte SS, Venkateshwarlu V. Effect of precursors on capsaicin Synthesis in Suspension Cultures of Capsicum annuum. Plant Tiss. Cult. 1993; 3: 67-70.
55. Lindsey K. Incorporation of [14C] phenylalanine and [14C] cinnamic acid into capsaicin in cultured cells of Capsicum frutescens. Phytochemistry. 1986; 25: 2793-2801.
56. Johnson TS, Ravishankar GA, Venkataraman LV. In vitro capsaicin production by immobilized cells and placental tissues of Capsicum annuum L. grown in liquid medium. Plant Sci. 1990; 70: 223-229.
57. Pershing LK, Reilly CA, Corlett JL, Crouch DJ. Effects of vehicle on the uptake and elimination kinetics of capsaicinoids in human skin in vivo. Toxicol. Appl. Pharmacol. 2004; 200: 73-81.
58. Suresh D, Srinivasan K. Tissue distribution and elimination of capsaicin, piperine and curcumin following oral intake in rats. Indian J. Med. Res. 2010; 131: 682-691.
59. Chanda S, Bashir M, Babbar S, Koganti A, Bley K. In vitro hepatic and skin metabolism of capsaicin. Drug Metab. Dispos. 2008; 36: 670-675.
60. Kawada 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.
61. Cortright DN, Szallasi A. Biochemical pharmacology of the vanilloid receptor TRPV1. Eur. J. Biochem. 2004; 271: 1814-1819.
62. Tominaga M, Tominaga T. Structure and function of TRPV1. Pflugers Arch. 2005; 451: 143-150.
63. Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D. Nature. 1997; 389: 816-824.
64. Liu M, Liu MC, Magoulas C, Priestley JV, Willmott NJ. Versatile regulation of cytosolic Ca2+ by vanilloid receptor I in rat dorsal root ganglion neurons. J. Biol. Chem. 2003; 278: 5462-5472.
65. Kárai LJ, Russell JT, Iadarola MJ, Oláh Z. Vanilloid receptor 1 regulates multiple calcium compartments and contributes to Ca2+ induced Ca2+ release in sensory neurons. J. Biol. Chem. 2004; 279: 16377-16387.
66. Morita A, Iwasaki Y, Kobata K, Lida T, Higashi T, Oda K, Susuki A, Narukawa M, Sasakuma S, Yokogoshi H, Yazawa S, Tominaga M, Watanabe T. Lipophilicity of capsaicinoids and capsinoids influences the multiple activation process of rat TRPV1. Life Sci. 2006; 79: 2303-2310.
67. Pingle SC, Matta JA, Ahern GP. TRPV1 a promiscuous TRP channel. Handb. Exp. Pharmacol. 2007; 179: 155-171.
68. Bevan S, Szolcsanyi J. Sensory neuron-specific actions of capsaicin: mechanisms and applications. Trends Pharmacol. Sci. 1990; 11: 330-333.
69. Saria A, Lundberg JM, Hua X, Lembeck F. Capsaicin-induced substance P release and sensory control of vascular permeability in the guinea-pig ureter. Neurosci. Lett. 1983; 41: 167-172.
70. Jhamandas K, Yaksh TL, Harty G, Szolcsanyi J, Go VL. Action of intrathecal capsaicin and its structural analogues on the content and release of spinal substance P: selectivity of action and relationship to analgesia. Brain Res. 1984; 306: 215-225.
71. Purkiss J, Welch M, Doward S, Foster K. Capsaicin-stimulated release of substance P from cultured dorsal root ganglion neurons: involvement of two distinct mechanisms. Biochem. Pharmacol. 2000; 59: 1403-1406.
72. Szolcsanyi J, Oroszi G, Nemeth J, Szilvassy Z, Tosaki A. Endothelin release by capsaicin in isolated working rat heart. Eur. J. Pharmacol. 1999; 376: 247-250.
73. Dutta A, Deshpande SB. Mechanisms underlying the hypertensive response induced by capsaicin. Int. J. Cardiol. 2010; 145: 358-359.
74. Fraenkel L, Jr Bogardus ST, Concato J, Wittink DR. Treatment options in knee osteoarthritis: the patient's perspective. Arch. Intern. Med. 2004; 164: 1299–1304.
75. Remadevi R, Szallisi A. Adlea (ALGRX-4975), an injectable capsaicin (TRPV1 receptor agonist) formulation for longlasting pain relief. IDrugs. 2008; 11: 120–132.
76. Knotkova H, Pappagallo M, Szallasi A. Capsaicin (TRPV1 agonist) therapy for pain relief: farewell or revival. Clin. J. Pain. 2008; 24: 142–154.
77. Surh YJ. More than spice: capsaicin in hot chili peppers makes tumor cells commit suicide. J. Natl Cancer Inst. 2002; 94: 1263–1265.
78. Oh SH, Kim YS, Lim SC, Hou YF, Chang IY, You HJ. Dihydrocapsaicin (DHC), a saturated structural analog of capsaicin, induces autophagy in human cancer cells in a catalase-regulated manner. Autophagy. 2008; 4: 1009–1019.
79. Thoennissen NH, O'Kelly J, Lu D, Iwanski GB, La DT, Abbassi S, Leiter A, Karlan B, Mehta R, Koeffler HP. Capsaicin causes cell-cycle arrest and apoptosis in ER-positive and -negative breast cancer cells by modulating the EGFR/HER-2 pathway. Oncogene. 2010; 29: 285–296.
80. Yang ZH, Wang XH, Wang HP, Hu LQ, Zheng XM, Li SW. Capsaicin mediates cell death in bladder cancer T24 cells through reactive oxygen species production and mitochondrial depolarization. Urology. 2010; 75: 735–741.
81. Ito K, Nakazato T, Yamato K, Miyakawa Y, Yamada T, Hozumi N, Segawa K, IkedaY, Kizaki M. Induction of apoptosis in leukemic cells by homovanillic acid derivative, capsaicin, through oxidative stress: implication of phosphorylation of p53 at Ser-15 residue by reactive oxygen species. Cancer Res. 2004; 64: 1071–1078.
82. Choi CH, Jung YK, Oh SH. Selective induction of catalase-mediated autophagy by dihydrocapsaicin in lung cell lines. Free Radic. Biol. Med. 2010; 49: 245–257.
83. Ghosh AK, Basu S. Fas-associated factor 1 is a negative regulator in capsaicin induced cancer cell apoptosis. Cancer Lett. 2010; 287: 142–149.
84. Oh S, Choi CH, Jung YK. ) Autophagy induction by capsaicin in malignant human breast cells is modulated by p38 and ERK mitogen-activated protein kinase and retards cell death by suppressing endoplasmic reticulum stress-mediated apoptosis. Mol. Pharmacol. 2010; 78: 114–125.
85. Zhang J, Nagasaki M, Tanaka Y, Morikawa S. Capsaicin inhibits growth of adult T-cell leukemia cells. Leuk. Res. 2003; 27: 275–283.
86. Singh S, Asad SF, Ahmad A, Khan NU, Hadi SM. Oxidative DNA damage by capsaicin and dihydrocapsaicin in the presence of Cu(II). Cancer Lett. 2001; 169: 139–146.
87. Kim S, Moon A. Capsaicin-induced apoptosis of H-ras-transformed human breast epithelial cells is Rac-dependent via ROS generation. Arch. Pharm. Res. 2004; 27: 845–849.
88. Baez S, Tsuchiya Y, Calvo A, Pruyas M, Nakamura K, Kiyohara C, Oyama M, Yamamoto M. Yamamoto M. Genetic variants involved in gallstone formation and capsaicin metabolism, and the risk of gallbladder cancer in Chilean women. World J. Gastroenterol. 2010; 16: 372–378.
89. Cui J, Himms-Hagen J. Long-term decrease in body fat and in brown adipose tissue in capsaicin-desensitized rats. Am. J. Physiol. 1992; 262: R568–R573.
90. Joo JI, Kim DH, Choi JW, Yun JW. Proteomic analysis for antiobesity potential of capsaicin on white adipose tissue in rats fed with a high fat diet. J. Proteome Res. 2010; 9: 2977–2987.
91. Leung FW. Capsaicin-sensitive intestinal mucosal afferent mechanism and body fat distribution. Life Sci. 2008; 83: 1–5.
92. Reinbach HC, Smeets A, Martinussen T, Moller P, Westerterp-Plantenga MS. Effects of capsaicin, green tea and CH-19 sweet pepper on appetite and energy intake in humans in negative and positive energy balance. Clin. Nutr. 2009; 28: 260–265.
93. Shin KO, Moritani TJ. Alterations of autonomic nervous activity and energy metabolism by capsaicin ingestion during aerobic exercise in healthy men. J. Nutr. Sci. Vitaminol. Tokyo. 2007; 53: 124–132.
94. Harada N, Okajima K. Effects of capsaicin and isoflavone on blood pressure and serum levels of insulin-like growth factor-I in normotensive and hypertensive volunteers with alopecia. Biosci. Biotechnol. Biochem. 2009; 73: 1456–1459.
95. Peng J, Li YJ. The vanilloid receptor TRPV1: role in cardiovascular and gastrointestinal protection. Eur. J. Pharmacol. 2010; 627: 1–7.
96. Zvara A, Bencsik P, Fodor G, Csont T, Jr Hackler L, Dux M, Furst S, Jancso G, Puskas LG, Ferdinandy P. Capsaicin-sensitive sensory neurons regulate myocardial function and gene expression pattern of rat hearts: a DNA microarray study. FASEB J. 2006; 20: 160–162.
97. Zhou Z, Peng J, Wang CJ, Li D, Li TT, Hu CP, Chen XP, Li YJ. Accelerated senescence of endothelial progenitor cells in hypertension is related to the reduction of calcitonin gene-related peptide. J. Hypertens. 2010; 28: 931–939.
98. Adams MJ, Ahuja KD, Geraghty DP. Effect of capsaicin and dihydrocapsaicin on in vitro blood coagulation and platelet aggregation. Thromb. Res. 2009; 124: 721–723.
99. Hogaboam CM, Wallace JL. Inhibition of platelet aggregation by capsaicin. An effect unrelated to actions on sensory afferent neurons. Eur. J. Pharmacol. 1991; 202: 129–131.
100. Harper AG, Brownlow SL, Sage SO. A role for TRPV1 in agonist-evoked activation of human platelets. J. Thromb. Haemost. 2009; 7: 330–338.
101. Ahuja KD, Ball MJ. Effects of daily ingestion of chilli on serum lipoprotein oxidation in adult men and women. Br. J. Nutr. 2006; 96: 239–242.
102. Wang L, Hu CP, Deng PY, Shen SS, Zhu HQ, Ding JS, Tan GS Li YJ. The protective effects of rutaecarpine on gastric mucosa injury in rats. Planta Med. 2005; 71: 416–419.
103. Nishihara K, Nozawa Y, Nakano M, Ajioka H, Matsuura N. Sensitizing effects of lafutidine on CGRP-containing afferent nerves in the rat stomach. Br. J. Pharmacol. 2002; 135: 1487–1494.
104. Serra MPM, Llorca CS, Donat FJS. Pharmacological treatment of burning mouth syndrome: A review and update. Med Oral Patol Oral Cir Bucal. 2007; 12; E299-304.
105. Naoaki AH, Kenji AO, Masatoku AA, Hiroki BK, Naomi N. Administration of capsaicin and isoflavone promotes hair growth by increasing insulin-like growth factor-I production in mice and in humans with alopecia. Growth Hormone & IGF Research. 2007; 17: 408–415.
106. Surh YJ, Lee SS. Capsaicin, a double-edged sword: Toxicity, metabolism, and chemopreventive potential. Life Sciences. 1995; 56: 1845-1855.
Published
01-10-2011
Statistics
Abstract Display: 578 
PDF Downloads: 777
Dimension Badge
How to Cite
“AN OVERVIEW ABOUT VERSATILE MOLECULE CAPSAICIN”. International Journal of Pharmaceutical Sciences and Drug Research, vol. 3, no. 4, Oct. 2011, pp. 280-6, https://doi.org/10.25004/IJPSDR.2011.030402.
Issue
Section
Review Article
Copyright (c) 2011 R Arora, N S Gill, G Chauhan, A C Rana
This work is licensed under a Creative Commons Attribution 4.0 International License.
How to Cite
“AN OVERVIEW ABOUT VERSATILE MOLECULE CAPSAICIN”. International Journal of Pharmaceutical Sciences and Drug Research, vol. 3, no. 4, Oct. 2011, pp. 280-6, https://doi.org/10.25004/IJPSDR.2011.030402.
