Ginsenosides in Liver Fibrosis: Pharmacological Actions and Therapeutic Potential

Liver fibrosis (LF) represents a critical pathological stage in the progression of various chronic liver diseases, and is characterized by the sustained activation of hepatic stellate cells (HSCs) and excessive deposition of extracellular matrix (ECM). These processes ultimately lead to cirrhosis and even hepatocellular carcinoma. Current therapeutic strategies for LF primarily rely on etiological interventions and supportive management. However, due to the complex pathogenesis of LF, involving multiple interconnected signaling pathways, effective and specific antifibrotic therapies remain lacking. Therefore, the development of multi-target and system-level therapeutic strategies for the treatment of LF is of considerable importance. Ginsenosides, the major bioactive components of Panax ginseng, exhibit multi-component and multi-target pharmacological properties and have shown broad potential in the prevention and treatment of liver fibrosis. Accumulating evidence indicates that several ginsenosides, including Rg1, Rb1, Rg3, Rh1, Rd, and the metabolite Compound K, exert significant antifibrotic effects across various experimental models. This review systematically summarizes the pharmacological mechanisms of ginsenosides in liver fibrosis and integrates their effects from a mechanistic perspective. Overall, ginsenosides directly target key fibrogenic processes by inhibiting HSCs activation and proliferation, promoting apoptosis, reducing ECM synthesis, and facilitating ECM degradation. In addition, they indirectly modulate fibrosis progression by regulating upstream amplifying factors such as inflammation, oxidative stress, and the immune microenvironment. Furthermore, ginsenosides also influence cell fate-related processes, including autophagy and ferroptosis, in a cell-type-dependent manner. In hepatocytes, maintaining appropriate autophagic activity and suppressing lipid peroxidation generally confers protective effects. In HSCs, by contrast, the inhibition of protective autophagy or induction of ferroptosis appears to be more relevant to antifibrotic efficacy. Although substantial experimental evidence supports the antifibrotic potential of ginsenosides, their clinical translation remains limited by low bioavailability, unclear active forms in vivo, and the lack of high-quality clinical studies. Future investigations should focus on identifying key molecular targets and underlying mechanisms through multi-omics approaches and structure–activity relationship analyses. Well-designed clinical trials should likewise be conducted to evaluate the safety and therapeutic efficacy of ginsenosides and, thereby, facilitate their clinical application in liver fibrosis.