Berberine (BBR) is an isoquinoline alkaloid extracted from the roots, rhizomes and stems of coptis. Liver fibrosis is a worldwide health problem with no established therapy until now. The aim of our study is to investigate the efficacy of BBR on hepatic fibrosis induced in rats and to uncover other mechanisms. Rats were injected with thioacetamide (TAA) (200 mg/kg, i.p) twice per week for 6 weeks to induce fibrosis. Treated groups were gavaged with BBR (50 mg/kg/day, p.o) simultaneously with TAA injection. Hepatic antioxidant enzymes (catalase, SOD, GPx) were assessed in hepatic homogenate. Their activities were attenuated by TAA injection and elevated by BBR administration. Additionally, serum IL-6 and mRNA levels of IL-1β, IL-6, IL-10 and IFN-γ were evaluated as inflammatory markers. Our results showed that BBR suppressed the inflammation induced by TAA injection. Tissue expression of α-SMA (marker of activated HSCs), TGF-β1 and fibronectin were measured by immunohistochemistry as well as mRNA expressions of TGF-β1 and fibronectin were quantified as fibrotic markers. The collagen deposition in hepatic tissues was assessed by Masson's trichome staining. BBR significantly alleviated TGF-β1 production, decreased collagen and fibronectin deposition and consequently attenuated hepatic fibrogenesis. Akt pathway controls cell survival, proliferation, migration and adhesion. The relative phosphorylation of Akt was determined in hepatic homogenates that was increased with TAA injection and decreased by BBR treatment. Inhibition of Akt pathway has been linked to the intrinsic pathway of apoptosis. Caspase-3, caspase-9, Bcl-2 and Bax were quantified as apoptotic markers using qPCR and also caspase-3 by immunohistochemistry. BBR-treated rats showed an increase in the expression of apoptotic markers. Moreover, BBR-treated rats showed restoration of normal liver lobular architecture as shown by H&E staining. In conclusion, BBR is a potential therapeutic candidate for liver fibrosis owing to its antioxidant and anti-inflammatory activities.

小ber碱（BBR）是从黄连的根，根茎和茎中提取的一种异喹啉生物碱。肝纤维化是一个全球性的健康问题，迄今为止尚无公认的治疗方法。我们研究的目的是研究BBR对大鼠肝纤维化的功效并揭示其他机制。每周两次向大鼠注射硫代乙酰胺（TAA）（200 mg / kg，ip），持续6周，以诱导纤维化。用TAA注射同时用BBR（50 mg / kg /天，口服）治疗组。在肝匀浆中评估肝抗氧化酶（过氧化氢酶，SOD，GPx）。它们的活性通过注射TAA减弱，而通过BBR施用而升高。另外，评估血清IL-6和IL-1β，IL-6，IL-10和IFN-γ的mRNA水平作为炎性标记。我们的结果表明，BBR抑制了TAA注射引起的炎症。用免疫组织化学法检测α-SMA（活化的HSCs的标志物），TGF-β1和纤连蛋白的组织表达，并定量TGF-β1和纤连蛋白的mRNA表达作为纤维化标志物。通过Masson的毛状体染色评估肝组织中的胶原蛋白沉积。BBR显着减轻了TGF-β1的产生，减少了胶原蛋白和纤连蛋白的沉积，从而减弱了肝纤维化的发生。Akt途径控制细胞存活，增殖，迁移和粘附。确定了肝匀浆中Akt的相对磷酸化水平，该匀浆水平随TAA注射而增加，而经BBR处理则降低。Akt途径的抑制与细胞凋亡的内在途径有关。Caspase-3，Caspase-9，Bcl-2和Bax定量使用qPCR和caspase-3作为凋亡标记物通过免疫组织化学。用BBR处理的大鼠显示出凋亡标记物表达的增加。此外，用BBR处理的大鼠显示出正常肝小叶结构的恢复，如H＆E染色所示。总之，由于其抗氧化剂和抗炎活性，BBR是肝纤维化的潜在治疗候选物。