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 degrees C. 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 degrees C, 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.