Lin Xingmei, Zhang Chengzhong, Huang Baokang
School of Pharmacy, Naval Medical University, Shanghai, 200433, China; School of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, China.
School of Pharmacy, Naval Medical University, Shanghai, 200433, China.
J Ethnopharmacol. 2025 Jan 30;337(Pt 2):118850. doi: 10.1016/j.jep.2024.118850. Epub 2024 Sep 24.
The herb of Abrus cantoniensis Hance (AC) is an important Traditional Chinese Medicine (TCM) and is also used as an herbal tea with hepatoprotective action. Soyasaponin Bb is one of the pharmacodynamic substances of AC for the herb's effective pharmacological activity. This study aims to investigate the anti-fibrotic and hepatoprotective activities of soyasaponin Bb in vivo and in vitro experiments, mechanism by network pharmacology and quantification by HPLC.
High-performance liquid chromatography (HPLC) was applied to evaluate the quality of the herb and determine the contents of soyasaponin Bb from different sources and parts of the AC. In vivo experiments were conducted to induce an acute liver injury model by injecting CCl into mice, and an in vitro hepatic fibrosis model was established by cultivating LX-2 cells with TGF-β. These models were used to explore the anti-fibrotic and hepatoprotective effects of soyasaponin Bb and its underlying mechanisms. In addition, the potential target genes corresponding to soyasaponin Bb were identified using the Swiss Target Prediction database through network pharmacology methods. Meanwhile, hepatic fibrosis targets were screened using the GeneCards, TTD, and OMIM disease databases. The STING database was used to construct the protein-protein interaction (PPI) network of soyasaponin Bb-hepatic fibrosis. The soyasaponin Bb-hepatic fibrosis disease target-pathway network was constructed using Cytoscape 3.9.1 software. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to enrich and analyze the common targets of the drug and the disease, aiming to identify the potential targets and pathways involved in the anti-fibrotic and hepatoprotective effects of soyasaponin Bb.
The content of soyasaponin Bb varied across different sources, with the roots containing the highest concentration, up to 0.2480%. In vivo experiments showed that soyasaponin Bb had a protective effect against CCl-induced acute liver injury, effectively inhibiting the increase in ALT and AST levels and slowing down the hepatocyte inflammatory damage caused by CCl. Soyasaponin Bb also down-regulated MDA levels and up-regulated SOD levels, indicating a certain antioxidant capacity. In vitro cell experiments showed that soyasaponin Bb could effectively inhibit the proliferation of HSC-LX2 cells induced by TGF-β by regulating the TGF-β/α-SMA pathway, significantly down-regulate the protein expression of TGF-β and α-SMA, while also reducing the levels of inflammatory cytokines IL-6 and IL-1β. Further network pharmacology analysis suggested that soyasaponin Bb can exert anti-fibrosis activity by regulating the IBD signaling pathway, Th17 signaling pathway, Hepatitis B signaling pathway, and JAK-STAT signaling pathway.
Soyasaponin Bb is primarily distributed in the root of AC, and it has a strong protective effect against CCl-induced acute liver injury. It can reduce the level of inflammatory factors, relieve inflammation, and exert anti-fibrotic activity by regulating the TGF-β/α-SMA pathway. Its potential anti-hepatic fibrosis mechanism has been investigated through network pharmacology.
鸡骨草（AC）是一种重要的传统中药，也被用作具有肝脏保护作用的草药茶。大豆皂苷Bb是鸡骨草发挥有效药理活性的药效物质之一。本研究旨在通过体内和体外实验研究大豆皂苷Bb的抗纤维化和肝脏保护活性，通过网络药理学探讨其作用机制，并通过高效液相色谱法进行定量分析。
采用高效液相色谱法（HPLC）评估鸡骨草药材质量，并测定不同来源和部位鸡骨草中大豆皂苷Bb的含量。体内实验通过向小鼠注射四氯化碳诱导急性肝损伤模型，体外实验通过用转化生长因子-β（TGF-β）培养LX-2细胞建立肝纤维化模型。利用这些模型探究大豆皂苷Bb的抗纤维化和肝脏保护作用及其潜在机制。此外，通过网络药理学方法，使用瑞士靶点预测数据库鉴定与大豆皂苷Bb相对应的潜在靶基因。同时，利用GeneCards、TTD和OMIM疾病数据库筛选肝纤维化靶点。使用STING数据库构建大豆皂苷Bb-肝纤维化的蛋白质-蛋白质相互作用（PPI）网络。使用Cytoscape 3.9.1软件构建大豆皂苷Bb-肝纤维化疾病靶点-通路网络。进行基因本体（GO）和京都基因与基因组百科全书（KEGG）分析，以富集和分析药物与疾病的共同靶点，旨在确定参与大豆皂苷Bb抗纤维化和肝脏保护作用的潜在靶点和通路。
不同来源的鸡骨草中大豆皂苷Bb含量不同，根部含量最高，可达0.2480%。体内实验表明，大豆皂苷Bb对四氯化碳诱导的急性肝损伤具有保护作用，有效抑制谷丙转氨酶（ALT）和谷草转氨酶（AST）水平的升高，并减缓四氯化碳引起的肝细胞炎症损伤。大豆皂苷Bb还下调丙二醛（MDA）水平，上调超氧化物歧化酶（SOD）水平，表明具有一定的抗氧化能力。体外细胞实验表明，大豆皂苷Bb可通过调节TGF-β/α-平滑肌肌动蛋白（α-SMA）通路有效抑制TGF-β诱导的肝星状细胞（HSC-LX2）增殖，显著下调TGF-β和α-SMA的蛋白表达，同时还降低炎症细胞因子白细胞介素-6（IL-6）和白细胞介素-1β的水平。进一步的网络药理学分析表明，大豆皂苷Bb可通过调节炎症性肠病（IBD）信号通路、辅助性T细胞17（Th17）信号通路、乙型肝炎信号通路和Janus激酶-信号转导和转录激活因子（JAK-STAT）信号通路发挥抗纤维化活性。
大豆皂苷Bb主要分布于鸡骨草根部，对四氯化碳诱导的急性肝损伤具有较强的保护作用。它可降低炎症因子水平，减轻炎症，并通过调节TGF-β/α-SMA通路发挥抗纤维化活性。已通过网络药理学研究了其潜在的抗肝纤维化机制。
