Capsaicin-like anti-obese activities of evodiamine from fruits of Evodia rutaecarpa, a vanilloid receptor agonist

Evodiamine, a major alkaloidal principle of Evodia fruits (Evodia rutaecarp a, 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 capsai cin 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 examin ed. When evodiamine was supplemented at 0.03% of the diet and fed to mice f or 12 days, the perirenal fat weight became significantly lower than in the control group. The epididymal fat mass was also decreased in the evodiamin e diet group. When evodiamine was supplemented at 0.02% in the form of etha nol extract of Evodia fruits to the high-fat diet and fed to rats for 21 da ys, the body weight, the perirenal fat weight, epididymal fat weight, the l evels 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 tiss ue mitochondria, as the biological index of enhanced heat production, were significantly increased in the evodiamine fed rats. Fasting mice subcutaneo usly administered 1-3 mg/kg evodiamine showed decreased core body temperatu re by 1-2 degreesC. This hypothermic effect was prevented by the pretreatme nt of intraperitoneally administered 10 mg/kg capsazepine, a vanilloid rece ptor antagonist. on the other hand, food-sated mice subcutaneously administ ered 1-3 mg/kg evodiamine showed unchanged core body temperature and increa sed tail skin temperature by more than 5 degreesC, suggesting the increased energy expenditure by enhanced heat dissipation. In conclusion, we have de monstrated that a novel non-pungent vanilloid receptor agonist, evodiamine, mimics the characteristic anti-obese effects induced by capsaicin. Evodiam ine would induce heat loss and heat production at the same time and dissipa te food energy, preventing the accumulation of perivisceral fat and the bod y weight increase.