Park Hyoung Joon, Lee Soo-Jung, Song Yuno, Jang Sun-Hee, Ko Yeoung-Gyu, Kang Suk Nam, Chung Byung Yeoup, Kim Hong-Duck, Kim Gon-Sup, Cho Jae-Hyeon
1 Institute of Life Science, College of Veterinary Medicine, Gyeongsang National University , Jinju, Korea.
J Med Food. 2014 Jan;17(1):103-10. doi: 10.1089/jmf.2013.2849.
Schisandra chinensis (SC), a traditional herbal medicine, has been prescribed for patients suffering from various liver diseases, including hepatic cancer, hypercholesterolemia, and CCl₄-induced liver injury. We investigated whether SC extract has a protective effect on alcohol-induced fatty liver and studied its underlying mechanisms. Rats were fed with ethanol by intragastric administration every day for 5 weeks to induce alcoholic fatty liver. Ethanol treatment resulted in a significant increase in alanine aminotransferase, aspartate aminotransferase, and hepatic triglyceride (TG) levels and caused fatty degeneration of liver. Ethanol administration also elevated serum TG and total cholesterol (TC) and decreased high-density lipoprotein (HDL) cholesterol levels. However, after administration of ethanol plus SC extracts, the ethanol-induced elevation in liver TC and TG levels was reversed. Elevation in serum TG was not observed after treatment with SC. Moreover, compared with the ethanol-fed group, the rats administered ethanol along with SC extracts for 5 weeks showed attenuated fatty degeneration and an altered lipid profile with decreased serum TC and TG, and increased HDL cholesterol levels. Chronic ethanol consumption did not affect peroxisome proliferator-activated receptor γ (PPARγ) levels, but it decreased PPARα and phospho-AMP-activated protein kinase (AMPK) levels in the liver. However, SC prevented the ethanol-induced decrease in PPARα expression and induced a significant decrease in sterol regulatory element-binding protein-1 expression and increase in phospho-AMPK expression in rats with alcoholic fatty liver. SC administration resulted in a significant decrease in intracellular lipid accumulation in hepatocytes along with a decrease in serum TG levels, and it reversed fatty liver to normal conditions, as measured by biochemical and histological analyses. Our results indicate that the protective effect of SC is accompanied by a significant increase in phospho-AMPK and PPARα expression in hepatic tissue of alcoholic rats, thereby suggesting that SC has the ability to prevent ethanol-induced fatty liver, possibly through activation of AMPK and PPARα signaling.
五味子是一种传统草药,已被用于治疗各种肝脏疾病患者,包括肝癌、高胆固醇血症和四氯化碳诱导的肝损伤。我们研究了五味子提取物对酒精性脂肪肝是否具有保护作用,并探讨了其潜在机制。通过每天灌胃给予大鼠乙醇,持续5周以诱导酒精性脂肪肝。乙醇处理导致丙氨酸转氨酶、天冬氨酸转氨酶和肝甘油三酯(TG)水平显著升高,并引起肝脏脂肪变性。乙醇给药还使血清TG和总胆固醇(TC)升高,高密度脂蛋白(HDL)胆固醇水平降低。然而,给予乙醇加五味子提取物后,乙醇诱导的肝脏TC和TG水平升高得到逆转。五味子处理后未观察到血清TG升高。此外,与乙醇喂养组相比,连续5周给予乙醇和五味子提取物的大鼠脂肪变性减轻,脂质谱改变,血清TC和TG降低,HDL胆固醇水平升高。长期摄入乙醇不影响过氧化物酶体增殖物激活受体γ(PPARγ)水平,但会降低肝脏中PPARα和磷酸化AMP激活蛋白激酶(AMPK)水平。然而,五味子可防止乙醇诱导的PPARα表达降低,并使酒精性脂肪肝大鼠的固醇调节元件结合蛋白-1表达显著降低,磷酸化AMPK表达增加。五味子给药导致肝细胞内脂质积累显著减少,同时血清TG水平降低,并通过生化和组织学分析将脂肪肝逆转至正常状态。我们的结果表明,五味子的保护作用伴随着酒精性大鼠肝组织中磷酸化AMPK和PPARα表达的显著增加,从而表明五味子可能通过激活AMPK和PPARα信号通路来预防乙醇诱导的脂肪肝。