Anti-Fibrotic Effect of Plumbagin on CCl4-Lesioned Rats

作者:Wei, Yanfei*; Huang, Minkui; Liu, Xuemei; Yuan, Zhang; Peng, Yue; Huang, Zhenqing; Duan, Xuelin; Zhao, Tiejian
来源:Cellular Physiology and Biochemistry, 2015, 35(4): 1599-1608.
DOI:10.1159/000373974

摘要

Background/Aims: Our previous studies have shown that plumbagin effectively inhibits hepatic stellate cell (HSC) proliferation. Thus, plumbagin-mediated anti-fibrotic effects in vivo merit further investigation. Methods: We used rat models to assess the potential benefits of plumbagin against CCl4-induced liver fibrosis. Results: The results showed that plumbagin lowered the serum concentrations of liver functional enzymes (ALT, AST, ALB, TBIL) in CCl4-fibrotic rats while reducing inflammatory cytokine levels (IL-6, TNF-alpha). As reflected in pathological examinations, rats that were administered plumbagin showed decreased collagen markers (HA, LN, PCIII and CIV) in liver tissues and improved hepatocellular impairments. In addition, plumbagin contributed to down-regulating NF-kappa B and TLR-4 mRNA in CCl4-lesioned livers. As revealed in the immunohistochemical assay, plumbagin-administered rats showed reduced levels of alpha-SMA and TNF-alpha immunoreactive cells in liver tissue. Conclusion: Collectively, these findings offer appealing evidence that plumbagin may serve as an anti-fibrotic medication through inactivating the NF-kappa B/TLR-4 pathway that is associated with inflammatory reactions, thereby mitigating liver fibrosis.