Treatment Rats With Jiangzhi Capsule Improves Liquid Fructose-Induced Fatty Liver:Modulation Of Hepatic Expression Of SREBP-1c And DGAT-2

Background Jiangzhi Capsule is a listed traditional Chinese medicine and has been used for abnormalities of lipid metabolism over ten years in Australia. To obtain better understanding Jiangzhi Capsule, the present study investigated the effects and underlying mechanisms of Jiangzhi Capsule on lipid abnormalities.Methods Male rats were treated with liquid fructose in their drinking water over 14 weeks. Jiangzhi Capsule was co-administered (once daily, by oral gavage) during the last 7 weeks. The indexes of lipid and glucose homeostasis were determined enzymatically, by ELISA and/or histologically. Gene expression was analyzed by Real-time PCR, Western blot and/or immunohistochemistry.Results Treatment with Jiangzhi Capsule (100 mg/kg) attenuated fructose-induced excessive triglyceride accumulation and Oil Red O-stained area in the liver. This effect was accompanied by amelioration of hyperinsulinemia. There was no significant difference in intakes of fructose and chow, and body weight between fructose control and fructose Jiangzhi Capsule-treated groups. Jiangzhi Capsule downregulated fructose-stimulated hepatic overexpression of sterol regulatory element binding protein (SREBP)-1/1c at the mRNA and protein levels. Accordingly, SREBP-1c downstream genes acetyl-CoA carboxylase (ACC)-1 and stearoyl-CoA desaturase (SCD)-1 were also inhibited. On the other hand, acyl-coenzyme A:diacylglycerol acyltransferase (DGAT)-2 expression at the mRNA and protein levels in the liver was also inhibited after Jiangzhi Capsule treatment. In contrast, Jiangzhi Capsule affected neither carbohydrate response element binding protein, peroxisome proliferator-activated receptor (PPAR)-gamma and DGAT-1, nor PPAR-alpha and its target genes.Conclusions These findings demonstrate the anti-steatotic action of Jiangzhi Capsule in fructose-fed rats, and modulation of hepatic SREBP-1c and DGAT-2 that involve fatty acid and triglyceride biosynthesis is responsible. Our findings provide a better mechanistic understanding of Jiangzhi Capsule for the treatment of fatty liver and its associated disorders.