慢性肝病,由于各种原因导致的长期状况,例如酗酒,代谢紊乱,和病毒性肝炎,正在成为一个重大的全球卫生挑战。绞股蓝皂甙(GP),源自中药绞股蓝(Thunb。)牧野,近年来表现出保护肝脏的特性,然而,确切的治疗机制仍不清楚。在这项研究中,采用无标记和平行反应监测(PRM)蛋白质组学方法阐明了GPs对肝损伤大鼠的肝保护机制。通过无标签蛋白质组学,我们鉴定了2104种与肝损伤相关的差异表达蛋白(DEP),以及1974年与全科医生影响有关的DEP。生物信息学分析显示,GP主要恢复涉及缬氨酸的代谢过程,亮氨酸,和异亮氨酸降解,以及丙酸和丁酸代谢,和肝损伤期间类固醇激素的生物合成。随后,重叠的两组DEP鉴定出在GP治疗后逆转的1508蛋白质,与PRM进一步验证的关键目标。确定了8种用于GP治疗肝损伤的靶蛋白,包括Lgals3,Psat1,Phgdh,Cyp3a9,Cyp2c11,Cyp4a2,Glul,Ces1d这些发现不仅阐明了全科医生的肝脏保护机制,但也可作为慢性肝病的潜在治疗靶点。
Chronic liver disease, a long-term condition resulting from various causes such as alcohol abuse, metabolic disorders, and viral hepatitis, is becoming a significant global health challenge. Gypenosides (GPs), derived from the traditional Chinese medicine Gynostemma pentaphyllum (Thunb.) Makino, exhibited hepatoprotective properties in recent years, yet the precise therapeutic mechanism remains unclear. In this study, label-free and parallel reaction monitoring (PRM) proteomics were used to elucidate the hepatoprotective mechanism of GPs in liver injury rats. Through label-free proteomics, we identified 2104 differentially expressed proteins (DEPs) associated with liver injury, along with 1974 DEPs related to the effects of GPs. Bioinformatics analysis revealed that GPs primarily restored metabolic processes involving valine, leucine, and isoleucine degradation, as well as propanoate and butanoate metabolism, and steroid hormone biosynthesis during liver injury. Subsequently, overlapping the two groups of DEPs identified 1508 proteins reversed following GPs treatment, with key targets further validated by PRM. Eight target proteins were identified for GPs treatment of liver injury, including Lgals3, Psat1, Phgdh, Cyp3a9, Cyp2c11, Cyp4a2, Glul, and Ces1d. These findings not only elucidated the hepatoprotective mechanism of GPs, but may also serve as potential therapeutic targets of chronic liver disease.