Evodiamine improves lipid profile in high-fat diet-fed mice by facilitating reverse cholesterol transport

OBJECTIVE Reverse cholesterol transport（RCT） is a pivotal pathway involved in transporting excess cholesterol from peripheral tissues to the liver for excretion in the bile and eventual y the feces. In the present study we identified the naturally occurring alkaloid evodiamine as alipid-lowing inducer by facilitating RCT in highfat diet（HFD）-fed mice. METHODS Hep G2 cells were first exposed to 0.6 m M FFA（palmitic acid/oleic acid, 1:2）for 24 h to induce the liversteatosis before treated with or without evodiamine foran additional 24 h. Atorvastatin was used as apositive control. Intracellular lipid deposition was analyzed by Oil Red O staining. Male ICR mice were fed HFD initially for 4 weeks to induce hyperlipidemia. After induction of hyperlipidemia, evodiamine was intragastrically administered in the dose of 10 mg · kg;per day for 4 weeks to the mice. The levels of triglyceride（TG）, total cholesterol（TC）, high-density lipoprotein cholesterol（HDL-C） and low-density lipoprotein cholesterol（LDL-C）in the serum were determinedto evaluate the metabolic lipid profiles in the HFD-fed mice. Hematoxylin and eosin（H&E） staining was performed for fat accumulation examination. Western blotting and quantitative real time polymerase chain reaction（q RT-PCR） were used to assess the expression of proteins and m RNAs correlated with RCT in the liver and small intestine, including ATP-binding cassette transporter A1（ABCA1）, ABCG1, ABCG5,ABCG8, scavenger receptor class B type 1（SR-B1） and Niemann-Pick type C1 Like 1（NPC1L1）. RESULTS Oil Red O staining revealed that evodiamine markedly attenuated hepatic fat accumulation caused by FFA in HepG2 cells. In HFD-fed mice, evodiamine significantly reduced serum TG, TC and LDL-C but not HDL-C. Besides, evodiamine significantly decreased hepatic lipid accumulation revealed by H&E staining. Moreover, evodiamine increased ABCG1 expression in the liver and raised NPC1L1 expression in the small intestine. CONCLUSION Evodiamine improves lipid metabolic profile in HFD-fed mice by increasing expression of ABCG1 in liver and NPC1L1 in the small intestine.