Planta Med 2001; 67(7): 628-633
DOI: 10.1055/s-2001-17353
Original Paper
© Georg Thieme Verlag Stuttgart · New York

Capsaicin-Like Anti-Obese Activities of Evodiamine from Fruits of Evodia rutaecarpa, a Vanilloid Receptor Agonist

Yoshinori Kobayashi*, Yumiko Nakano, Miho Kizaki, Kiyoko Hoshikuma, Yoshiharu Yokoo, Toshikazu Kamiya
  • Kyowa Hakko Kogyo Co., Ltd. Tsukuba Research Laboratories, Ibaraki, Japan
Further Information

Publication History

September 29, 2000

December 16, 2000

Publication Date:
24 September 2001 (online)


Evodiamine, a major alkaloidal principle of Evodia fruits (Evodia rutaecarpa, Rutaceae), showed vanilloid receptor agonistic activities comparable to capsaicin. The Chinese literature refers to Evodia fruits as a ”hot nature” herb. In spite of the similarities in the actions of evodiamine and capsaicin in vitro, evodiamine has no perceptible taste, including a peppery hot taste. Therefore, the effectiveness of evodiamine and the extract of Evodia fruits in preventing obesity on male C3H mice, or male SD rats were examined. When evodiamine was supplemented at 0.03 % of the diet and fed to mice for 12 days, the perirenal fat weight became significantly lower than in the control group. The epididymal fat mass was also decreased in the evodiamine diet group. When evodiamine was supplemented at 0.02 % in the form of ethanol extract of Evodia fruits to the high-fat diet and fed to rats for 21 days, the body weight, the perirenal fat weight, epididymal fat weight, the levels of serum free fatty acid, total lipids in the liver, triglyceride in the liver, and cholesterol level in the liver were significantly reduced as compared with the control diet group. Furthermore, both lipolytic activity in the perirenal fat tissue and specific GDP binding in brown adipose tissue mitochondria, as the biological index of enhanced heat production, were significantly increased in the evodiamine fed rats. Fasting mice subcutaneously administered 1-3 mg/kg evodiamine showed decreased core body temperature by 1 - 2 oC. This hypothermic effect was prevented by the pretreatment of intraperitoneally administered 10 mg/kg capsazepine, a vanilloid receptor antagonist. On the other hand, food-sated mice subcutaneously administered 1-3 mg/kg evodiamine showed unchanged core body temperature and increased tail skin temperature by more than 5 oC, suggesting the increased energy expenditure by enhanced heat dissipation. In conclusion, we have demonstrated that a novel non-pungent vanilloid receptor agonist, evodiamine, mimics the characteristic anti-obese effects induced by capsaicin. Evodiamine would induce heat loss and heat production at the same time and dissipate food energy, preventing the accumulation of perivisceral fat and the body weight increase.


  • 1 Lamarche B. Abdominal obesity and its metabolic complications: implications for the risk of ischaemic heart disease.  Coronary Artery Disease. 1998;  9 473-81
  • 2 Kawada T, Hagiwara K, Iwai K. Effect of capsaicin on lipid metabolism in rats fed a high fat diet.  Journal of Nutrition. 1986;  116 1272-8
  • 3 Yoshida T, Yoshikawa K, Wakabayashi Y, Nishioka H, Kondo M. Effects of capsaicin and isothiocyanate on thermogenesis of interscapular brown adipose tissue in rats.  Journal of Nutritional Science and Vitaminology. 1988;  34 587-94
  • 4 Watanabe T, Kawada T, Kato T, Harada T, Iwai K. Effects of capsaicin analogs on adrenal catecholamine secretion in rats.  Life Science. 1994;  54 369-74
  • 5 Kobayashi Y, Nakano Y, Hoshikuma K, Yokoo Y, Kamiya T. The bronchoconstrictive action of evodiamine, an indoloquinazoline alkaloid isolated from the fruits of Evodia rutaecarpa, on guinea-pig isolated bronchus: Possible involvement of vanilloid receptors.  Planta Medica. 2000;  66 526-30
  • 6 Kobayashi Y, Hoshikuma K, Nakano Y, Yokoo Y, Kamiya. The positive inotropic and chronotropic efects of evodiamine and rutaecarpine, indoloquinazoline alkaloids iisolated from the fruits of Evodia rutaecarpa, on the guinea pig isolated right atria: Possible involvement of vanilloid receptors.  Planta Medica. 2001;  67 244-8
  • 7 Suzuki M, Saitoh S, Yashiro M, Hariu J. Dietary effects on liver and muscle glycogen repletion in exhaustively exercised rats: energy composition and type of complex carbohydrates.  Journal of Nutritional Science and Vitaminology. 1984;  30 453-66
  • 8 Cannon B, Lindberg O. Mitochondria from brown adipose tissue: isolation and properties.  Methods in Enzymology. 1978;  55 65-78
  • 9 Kamiryo T. Peroxisome. In: Mohri H, Kagawa Y (eds.) Jikken Seibutsugaku Kohza. Maruzen Tokyo; 1984; 6: 125-126
  • 10 Nicholls D G. Hamster brown-adipose-tissue mitochondria. Purine nucleotide control of the ion conductance of the inner membrane, the nature of the nucleotide binding site.  European Journal of Biochemistry. 1976;  62 223-8
  • 11 Folch J, Lees M, Sloane-Stanley G H. A simple method for the isolation and purification of total lipids from animal tissues.  Journal of Biological Chemistry. 1957;  226 497-509
  • 12 Shimizu Y, Saito M. Activation of brown adipose tissue thermogenesis in recovery from anesthetic hypothermia in rats.  American Journal of Physiology. 1991;  261 R301-4
  • 13 Chiou W F, Chou C J, Shum A Y, Chen C F. The vasorelaxant effect of evodiamine in rat isolated mesenteric arteries: mode of action.  European Journal of Pharmacology. 1992;  215 277-83
  • 14 Chiou W F, Liao J F, Chen C F. Comparative study of the vasodilatory effects of three quinazoline alkaloids isolated from Evodia rutaecarpa .  Journal of Natural Products. 1996;  59 374-8
  • 15 Tsai T H, Lee T F, Chen C F, Wang L CH. Thermoregulatory effects of alkaloids isolated from Wu-chu-yu in afebrile and febrile rats.  Pharmacology, Biochemistry and Behavior. 1995;  50 293-8
  • 16 Kano Y, Zong Q N, Komatsu K. Pharmacological properties of galenical preparation. XIV. Body Temperature retaining effect of the Chinese traditional medicine, ”goshuyu-to” and component crude drugs.  Chemical & Pharmaceutical Bulletin (Tokyo). 1991;  39 690-2
  • 17 Hayes A G, Oxford A, Reynolds M, Shingler A H, Skingle M, Smith C, Tyres M B. The effects of series of capsaicin analogues on nociception and body temperature in the rat.  Life Science. 1984;  34 1241-8
  • 18 Rubino A, Burnstock G. Capsaicin-sensitive sensory-motor neurotransmission in the peripheral control of cardiovascular function.  Cardiovascular Research. 1996;  31 467-9
  • 19 Barton C, York D A, Bray G A. Bombesin-induced hypothermia in rats tested at normal ambient temperatures: contribution of the sympathetic nervous system.  Brain Research Bulletin. 1995;  37 163-8

Yoshinori Kobayashi Ph. D.

Kyowa Hakko Kogyo Co., Ltd.

Tsukuba Research Laboratories

2, Miyukigaoka, Tsukuba-shi,

Ibaraki 305-0841



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