Multi-target Mechanisms and Clinical Evidence for Ganzaoning Granule in Metabolic Dysfunction-Associated Steatotic...

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly discussed largely under the non-alcoholic fatty liver disease (NAFLD) framework, is now one of the most common chronic liver diseases worldwide. Its progression from simple steatosis to metabolic dysfunction-associated steatohepatitis (MASH), fibrosis, cirrhosis, and hepatocellular carcinoma (HCC) reflects the interaction of lipid overload, insulin resistance, oxidative stress, immune activation, hepatic stellate cell activation, and oncogenic remodeling. Although resmetirom and glucagon-like peptide-1 receptor agonist-based strategies have recently advanced the treatment landscape for selected patients with MASH and fibrosis, many patients remain outside the indications of current drug therapy, and safe adjunctive strategies across earlier disease stages remain an unmet need. Ganzaoning granule is a traditional Chinese medicine formulation derived from the anti-HCC precursor formula Ganfujian and has been used clinically in China for fatty liver disease and related chronic liver conditions. This narrative review summarizes the available evidence on Ganzaoning, including its phytochemical profile, network pharmacology findings, preclinical studies, and clinical observations in MASLD/NASH populations. Existing studies suggest that Ganzaoning or its related active fractions may modulate lipid metabolism through the AMP-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) axis, attenuate inflammatory signaling involving nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) and advanced glycation end-product (AGE)-receptor for advanced glycation end-product (RAGE) pathways, and influence fibrosis- and hepatocarcinogenesis-related molecular processes. However, much of the mechanistic evidence remains preclinical or inferred from network pharmacology, and the clinical evidence is limited by single-center designs, short follow-up, composite endpoints, and limited use of histological or advanced imaging outcomes. We therefore position Ganzaoning as a biologically plausible candidate adjunctive therapy rather than an established MASLD treatment. Future research should prioritize standardized product quality control, pharmacokinetic and pharmacodynamic characterization, herb-drug interaction assessment, and multicenter, double-blind, placebo-controlled trials using accepted MASLD endpoints.