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

Abstract

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.

Inhibitory effect of evodiamine alone and in combination with rosiglitazone on in vitro adipocyte differentiation and in vivo obesity related to diabetes

“…36 Evo showed an antiobesity effect in C57BL/6J mice fed on 60% high fat diets over 2 months in our preliminary study and recent report. 26,37 In an effort to find a therapeutic drug that effectively minimizes the potential side effects of rosi while preserving the insulin sensitivity effects, we evaluated the effects of evo on adipogenesis and T2DM in the in vitro and in vivo assays conducted herein.…”

“…When evo was administered for 7 weeks, blood glucose levels were reduced in mice with diet-induced obesity, 26 whereas the serum glucose levels remained unchanged in the SpragueDawley rats treated for 3 weeks with evo. 37 This controversy may be attributed to the different genetic backgrounds of animals, the duration of drug administration and fasting or nonfasting effects. As to serum biochemistry, the evo group evidenced significant improvements in serum insulin and NEFA levels compared to those of the control group.…”

Evodiamine improves congnitive abilities in SAMP8 and APPswe/PS1ΔE9 transgenic mouse models of Alzheimer's disease

“…Evodiamine has been shown to have various effects on biological processes, such as testosterone [28] and catecholamine secretion [29] , as well as vasodilative [30] , anti-nociceptive [31] , obesity [20] , and thermoregulatory and uterotonic effects [32] . Evodiamine has anti-tumor potential through its ability to inhibit proliferation, induce apoptosis and reduce invasion and metastasis of a wide variety of tumor cells, including breast cancer, prostate cancer, leukemic T-lymphocyte, melanoma, cervical cancer, colon cancer and lung cancer cells [33] .…”

“…The WT and vehicle groups received a standard diet and the treated groups received a standard diet plus the respective monomers at the doses described in Table 1. The doses of 12 individual herbal monomers were selected based on human-equivalent dosages and data in previous reports [13,14,16,20] . Morris water-maze tests were performed after 4 weeks of treatment, since this time period was believed sufficient for APP swe /PS1 ΔE9 transgenic mice to show significant impairments in function when compared with WT mice.…”

Anti-obesity effects of herbal extract YY312 in C57BL/6 mice fed a high-fat diet and 3T3-L1 cells

“…吳茱萸는 溫裏藥에 속하며 동 배속인 小茴香의 항비만 효 과가 보고된 바 있다 34) . 吳茱萸는 肝, 脾, 胃, 腎經에 작용하 며 大熱燥烈하여 疏肝下氣에 뛰어나 疏肝解鬱, 行氣燥濕하는 작용이 있고 15) , 주요 알칼로이드인 evodiamine의 capsaicin 과 유사한 항비만 효과가 보고된 바 있어 26) , 항비만 효과를 보인 것으로 사료된다.…”