Pien-Tze-Huang ameliorates hepatic fibrosis via suppressing NF-κB pathway and promoting HSC apoptosis

Ethnopharmacological relevance: Pien Tze Huang (PZH), a Chinese herbal formula, has various forms of pharmacological activity including anti-inflammation, liver protection and anti-tumor. Aim of the study: To investigate the anti-hepatic fibrosis effect of PZH and its potential mechanisms on experimental animal model of hepatic fibrosis and hepatic stellate cell (HSC). Material and methods: Rats were intraperitoneally administered with CCl4 to induce hepatic fibrosis and were simultaneously treated with PZH. Liver pathology were observed by hematoxylin and eosin (H&E) staining and Masson staining. Serum pro-inflammatory cytokines were determined by enzyme-linked immunosorbent assay (ELISA) kits. Moreover, the effects of PZH on HSC proliferation and apoptosis were assessed via MTT, flow cytometry and immunofluorescence analysis. Nuclear factor-kappa B (NF-kappa B) pathway activation and Bcl-2 family members were evaluated by reverse transcription quantitative polymerase chain reaction (real-time PCR) and western blotting. Result PZH significantly alleviated CCl4-induced liver injury, inflammation and fibrogenesis in rats. PZH also markedly decreased the production of hepatic-fibrosis biomarker, including ALT, AST, IV collagen and PCIII (Procollagen III), as well as inflammatory cytokines such as IL-1 beta, IL-6 and TNF-alpha. Importantly, PZH strongly inhibited HSC proliferation correlated with cell apoptosis induction as evidenced by modulating Bcl-2 family members and caspase activity. Moreover, PZH administration significantly increased the expression I kappa B-alpha, an inhibitor of NF-kappa B and suppressed expression of anti-apoptotic genes (Bcl-2, etc.). Collectively, these results suggested that PZH could promote HSC apoptosis through inhibiting NF-kappa B signaling pathway. Conclusion: Our study demonstrates that PZH ameliorates hepatic fibrosis and inflammation, chiefly through suppressing the NF-kappa B pathway and promoting HSC apoptosis. PZH is more likely to be a promising antifibrotic agent in chronic disease.