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

Abstract

Ethnopharmacological relevancePien Tze Huang (PZH), a Chinese herbal formula, has various forms of pharmacological activity including anti-inflammation, liver protection and anti-tumor. Aim of the studyTo 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 methodsRats 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-κB (NF-κB) pathway activation and Bcl-2 family members were evaluated by reverse transcription quantitative polymerase chain reaction (real-time PCR) and western blotting. ResultPZH 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-1β, IL-6 and TNF-α. 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 IκB-α, an inhibitor of NF-κB and suppressed expression of anti-apoptotic genes (Bcl-2, etc.). Collectively, these results suggested that PZH could promote HSC apoptosis through inhibiting NF-κB signaling pathway. ConclusionOur study demonstrates that PZH ameliorates hepatic fibrosis and inflammation, chiefly through suppressing the NF-κB pathway and promoting HSC apoptosis. PZH is more likely to be a promising antifibrotic agent in chronic disease.