Department of Epidemiology and Biostatistics, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, China.
West China-PUMC C.C. Chen Institute of Health, Sichuan University, Chengdu 610041, China.
Biosci Rep. 2022 Jul 29;42(7). doi: 10.1042/BSR20221030.
Chaihu-Shugan-San (CHSGS), a noted traditional Chinese medicine formula, has been used as a complementary and alternative therapy for liver fibrosis. However, the antifibrotic mechanisms of CHSGS still remain unclear. Thus, we used network pharmacology approach in combination with single cell and bulk transcriptomics to elucidate the antifibrotic mechanisms of CHSGS. We first screened out 134 bioactive ingredients of CHSGS through the defined criteria. Then, 1150 genes were predicted to be targets for CHSGS, while 625 liver fibrosis-associated genes were identified by single cell transcriptomics analysis. Next, 71 intersecting genes of CHSGS and liver fibrosis were defined as the therapeutic targets in CHSGS against liver fibrosis. Further, 21 core targets and 12 core ingredients of CHSGS against liver fibrosis were also identified. Meanwhile, enrichment analyses of core targets highlighted that the key mechanisms of CHSGS against liver fibrosis include modulation of inflammation responses, inhibition of angiogenesis, and regulation of ECM remodeling, of which the most important mechanism was the regulation of ECM remodeling. The molecular docking simulation validated strong binding affinity between the core targets and core ingredients. Furthermore, 62-gene signature may be used for determining the prognosis in cirrhotic patients based on the results of ssGSEA-Cox analysis. In conclusion, the present study revealed the multiple pharmacological targets and therapeutic mechanisms of CHSGS against liver fibrosis, which may thus serve as an effective antifibrotic therapy. Meanwhile, CHSGS may improve survival of patients with liver cirrhosis by the interaction of 62-gene signature.
柴芍疏肝散（CHSGS）是一种著名的中药方剂，已被用作肝纤维化的辅助和替代疗法。然而，CHSGS 的抗纤维化机制仍不清楚。因此，我们使用网络药理学方法结合单细胞和批量转录组学来阐明 CHSGS 的抗纤维化机制。我们首先通过定义的标准筛选出 CHSGS 的 134 种生物活性成分。然后，预测到 1150 个 CHSGS 的靶基因，而通过单细胞转录组学分析鉴定出 625 个与肝纤维化相关的基因。接下来，将 CHSGS 和肝纤维化的 71 个交集基因定义为 CHSGS 治疗肝纤维化的治疗靶点。此外，还确定了 CHSGS 抗肝纤维化的 21 个核心靶标和 12 个核心成分。同时，核心靶标的富集分析强调了 CHSGS 抗肝纤维化的关键机制包括调节炎症反应、抑制血管生成和调节 ECM 重塑，其中最重要的机制是调节 ECM 重塑。分子对接模拟验证了核心靶标和核心成分之间具有很强的结合亲和力。此外，根据 ssGSEA-Cox 分析的结果，62 个基因特征可能用于确定肝硬化患者的预后。总之，本研究揭示了 CHSGS 抗肝纤维化的多种药理靶标和治疗机制，因此可能作为一种有效的抗纤维化治疗方法。同时，CHSGS 可能通过 62 个基因特征的相互作用改善肝硬化患者的生存。
