Bai Junjie, Yang Zhongqiu, Wang Pengru, Qian Baolin, Jiang Zhonghao, Xu Tongjie, Pu Haiyan, Ye Mingxin, Du Yichao, Fu Wenguang
Department of General Surgery (Hepatopancreatobiliary Surgery, Biliary-Pancreatic Center), The Affiliated Hospital, Southwest Medical University, Luzhou, China.
Department of General Surgery, Dazhou Central Hospital, Dazhou, China.
Food Funct. 2025 Jun 16;16(12):4822-4836. doi: 10.1039/d5fo01024a.
Liver fibrosis is a pathological process characterized by the excessive deposition of diffuse extracellular matrix in the liver, serving as a reparative response of the body to chronic liver injury. Daidzein (DAI) is an isoflavone compound primarily derived from leguminous plants, such as soybeans and kudzu root. Numerous studies have demonstrated its significant anti-inflammatory and antioxidant properties; however, the extent of its role in anti-hepatic fibrosis remains uncertain. This study aimed to investigate whether DAI exerts a therapeutic effect on liver fibrosis and to elucidate its underlying molecular mechanisms. In this study, we primarily investigated the anti-hepatic fibrosis effects of DAI. We established two mouse models of liver fibrosis through intraperitoneal injection of carbon tetrachloride (CCl) and bile duct ligation (BDL). Following serum-free treatment, we administered transforming growth factor β1 to stimulate LX-2 cells, thereby creating a model for the activation of hepatic stellate cell (HSC) lines. DAI mitigated liver injury induced by CCl and BDL, as evidenced by decreased serum levels of aspartate aminotransferase, alanine aminotransferase, and liver hydroxyproline. Furthermore, DAI also diminished the inflammatory response associated with CCl and BDL. Additionally, DAI reduced the expression of α-smooth muscle actin and type I collagen, alpha 1, demonstrating anti-hepatic fibrosis effects by lowering the expression of integrin alphaV, integrin beta1, and YAP, while simultaneously increasing the protein expression of phosphorylated YAP (Ser 397). The use of the YAP inhibitor verteporfin in LX-2, along with YAP silencing treatment, confirmed that DAI inhibits the activation of HSCs through the regulation of YAP. This study demonstrated that DAI can mitigate liver injury and inflammatory responses induced by CCl and BDL. It inhibited the activation of HSCs and reduced liver fibrosis by targeting the integrin/YAP signaling pathway. These findings suggested that DAI may serve as a potential candidate for anti-hepatic fibrosis chemical drugs.
肝纤维化是一种病理过程，其特征为肝脏中弥漫性细胞外基质过度沉积，是机体对慢性肝损伤的一种修复反应。大豆苷元（DAI）是一种主要来源于豆科植物（如大豆和葛根）的异黄酮化合物。众多研究已证实其具有显著的抗炎和抗氧化特性；然而，其在抗肝纤维化中的作用程度仍不确定。本研究旨在探讨DAI是否对肝纤维化具有治疗作用，并阐明其潜在的分子机制。在本研究中，我们主要研究了DAI的抗肝纤维化作用。我们通过腹腔注射四氯化碳（CCl）和胆管结扎（BDL）建立了两种肝纤维化小鼠模型。在无血清处理后，我们给予转化生长因子β1刺激LX-2细胞，从而建立肝星状细胞（HSC）系激活模型。DAI减轻了CCl和BDL诱导的肝损伤，血清天冬氨酸氨基转移酶、丙氨酸氨基转移酶和肝脏羟脯氨酸水平降低证明了这一点。此外，DAI还减轻了与CCl和BDL相关的炎症反应。此外，DAI降低了α-平滑肌肌动蛋白和I型胶原蛋白α1的表达，通过降低整合素αV、整合素β1和YAP的表达显示出抗肝纤维化作用，同时增加了磷酸化YAP（Ser 397）的蛋白表达。在LX-2中使用YAP抑制剂维替泊芬以及YAP沉默处理证实，DAI通过调节YAP抑制HSC的激活。本研究表明，DAI可以减轻CCl和BDL诱导的肝损伤和炎症反应。它通过靶向整合素/YAP信号通路抑制HSC的激活并减轻肝纤维化。这些发现表明，DAI可能是抗肝纤维化化学药物的潜在候选物。
