Immunometabolic pathways in liver fibrosis: current evidence for selected plant-derived metabolites associated with traditional Chinese medicine

Abstract

Liver fibrosis is a progressive consequence of chronic hepatic injury characterized by sustained activation of hepatic stellate cells (HSCs) within a complex network of metabolic and inflammatory signaling. This review critically examines selected plant-derived metabolites associated with herbs used in Traditional Chinese Medicine (TCM), including salvianolic acid B, curcumin, berberine, resveratrol, puerarin, glycyrrhizin, tetrandrine, oroxylin A, and schisandrin B, for their potential roles in modulating immunometabolic pathways relevant to fibrogenesis. A structured search of PubMed and Web of Science identified mechanistic, preclinical, and clinical studies. Overall, these compounds were reported to influence key pathways implicated in liver fibrogenesis, including glycolysis, mitochondrial dysfunction, lipid metabolism, NF-κB, TGF-β/Smad, PI3K–Akt–mTOR, and HIF-1α signaling. However, the strength of evidence varies considerably across compounds. Curcumin and resveratrol have the most consistent translational data, whereas salvianolic acid B, tetrandrine, and oroxylin A remain supported primarily by preclinical findings with limited mechanistic and clinical validation. Current evidence is constrained by model heterogeneity, reliance on associative pathway analyses, and the scarcity of histologically confirmed clinical outcomes. These findings suggest that selected phytochemicals associated with TCM herbs may modulate immunometabolic processes involved in liver fibrosis, but their therapeutic potential remains incompletely defined and requires confirmation in standardized, mechanistically informed clinical studies.