Wang Hai-Qiao, Wan Zhong, Zhang Qiqiang, Su Tong, Yu Dan, Wang Fei, Zhang Chao, Li Wei, Xu Dongliang, Zhang Hai
Department of Traditional Chinese Medicine, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201112, China.
Department of Urology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200120, China.
Phytomedicine. 2022 Apr;98:153960. doi: 10.1016/j.phymed.2022.153960. Epub 2022 Jan 29.
Lignans, the major bioactive components of Schisandra chinensis, displays an anti-liver fibrosis effect. However, which one is the most effective lignan and what is its molecular mechanisms are still unclear.
This research aimed to screen the most effective components of lignans, identify and verify its pharmacological target, and investigate its molecular mechanism against liver fibrosis.
First, the most effective lignans were screened by a comprehensive RAW264.7/CMC system and LPS-induced RAW264.7. Second, the potential targets were predicted by a liver fibrosis domain-specific chemo-genomics knowledgebase and further verified by competition binding assay. Third, the effect of anti-liver fibrosis was evaluated by employing RAW264.7, co-cultured hepatic stellate cells (HSC) and CCl-induced liver fibrosis CB2 mice. The qPCR, ELISAs, western blot analyses, and immunofluorescence were used to evaluate the expression of main inflammatory factors and key proteins in NF-κB and p38 MAPK pathway.
Schisandrin B was identified as the most effective component for attenuating liver fibrosis, and CB2 was proven to be a potential target for anti-liver fibrosis. The in vitro and in vivo assays indicated that schisandrin B ameliorated CCl-induced liver fibrosis through suppressing NF-κB and p38 MAPK pathway in Kupffer cells by targeting CB2 receptor CONCLUSION: Schisandrin B targets CB2 receptor to inhibit Kupffer cell polarization by downregulating the NF-κB and p38 MAPK signaling pathways for ameliorating liver fibrosis.
五味子的主要生物活性成分木脂素具有抗肝纤维化作用。然而，哪种木脂素最有效及其分子机制仍不清楚。
本研究旨在筛选木脂素的最有效成分，鉴定并验证其药理靶点，探讨其抗肝纤维化的分子机制。
首先，通过综合RAW264.7/CMC系统和脂多糖诱导的RAW264.7筛选最有效的木脂素。其次，通过肝纤维化领域特异性化学基因组学知识库预测潜在靶点，并通过竞争结合试验进一步验证。第三，采用RAW264.7、共培养的肝星状细胞（HSC）和CCl诱导的肝纤维化CB2小鼠评估抗肝纤维化作用。采用qPCR、酶联免疫吸附测定、蛋白质免疫印迹分析和免疫荧光法评估NF-κB和p38丝裂原活化蛋白激酶（MAPK）途径中主要炎症因子和关键蛋白的表达。
五味子醇乙被确定为减轻肝纤维化的最有效成分，CB2被证明是抗肝纤维化的潜在靶点。体外和体内试验表明，五味子醇乙通过靶向CB2受体抑制库普弗细胞中的NF-κB和p38 MAPK途径，从而改善CCl诱导的肝纤维化。
五味子醇乙靶向CB2受体，通过下调NF-κB和p38 MAPK信号通路抑制库普弗细胞极化，从而改善肝纤维化。
