Natural bear bile has been used for liver disease in East Asia for thousands of years. However, its use has restrictions. In the current study, the therapeutic effects and potential mechanisms of cultured bear bile powder (CBBP) against hepatic fibrosis were evaluated in a dimethylnitrosamine (DMN)-induced rat model. CBBP treatment significantly improved DMN-induced hepatic necrosis and inflammatory infiltration. Additionally, CBBP remarkably alleviated the increased hepatic collagen content and expression of alpha-smooth muscle actin. Serum metabolomics revealed that 14 serum metabolites, including docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) were decreased in DMN-treated rats, which was reversed by CBBP. Pathway analyses revealed that the main metabolic pathways affected by CBBP were related to fatty acid biosynthesis and metabolism, and biosynthesis of unsaturated fatty acids. EPA and DHA are ligands of peroxisome proliferator activated receptors (PPARs). CBBP treatment significantly stimulated liver mRNA and protein expression of PPAR alpha and PPAR gamma. CBBP also markedly increased liver expression of PPAR alpha target genes, which are involved in fatty acid beta-oxidation, and down-regulated IL-6, a downstream inflammatory gene of PPAR gamma. In conclusion, CBBP has the potential to attenuate liver fibrosis and its mechanism involves the promotion of the liver expression of PPAR alpha and PPAR gamma. Our results may help in the development of a novel substitute for bear bile and therapeutic strategies for fibrotic liver diseases.
[1]Shanghai Univ Tradit Chinese Med, Sch Pharm, Dept Pharmacol, 1200 Cailun Rd, Shanghai 201203, Peoples R China.
[2]Shanghai Univ Tradit Chinese Med, Ctr Tradit Chinese Med Complex Syst, Shanghai, Peoples R China.
[3]Shanghai Kai Bao Pharmaceut CO Ltd, Shanghai 201401, Peoples R China.
[4]Shanghai Univ Tradit Chinese Med, Inst Chinese Mat Med, Shanghai Key Lab Complex Prescript, 1200 Cailun Rd, Shanghai 201203, Peoples R China.
[5]Shanghai Univ Tradit Chinese Med, Inst Chinese Mat Med, MOE Key Lab Standardisat Chinese Med, 1200 Cailun Rd, Shanghai 201203, Peoples R China.
[6]Shanghai Univ Tradit Chinese Med, Shanghai Key Lab Compound Chinese Med, Shanghai 201203, Peoples R China.
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