Antifibrotic and Hepatoprotective Potentials of Physalis Extracts in Liver Fibrosis: A Systematic Review

Liver fibrosis is a progressive pathological process characterized by excessive accumulation of extracellular matrix components, primarily collagen, as a result of chronic liver injury from various etiologies such as viral hepatitis, alcohol abuse, non-alcoholic steatohepatitis (NASH), and exposure to hepatotoxic agents. Persistent liver fibrosis can advance to cirrhosis, liver failure, and hepatocellular carcinoma, making it a major global health problem with limited therapeutic options. Currently, most available treatments target the underlying cause rather than directly reversing fibrogenesis, highlighting the urgent need for novel antifibrotic and hepatoprotective agents. Natural products have gained significant attention as potential sources of therapeutic compounds due to their broad biological activities and favorable safety profiles. Physalis species are rich in bioactive compounds such as withanolides, physalins, and flavonoids, which have demonstrated antioxidant, anti-inflammatory, immunomodulatory, and cytoprotective properties in preclinical studies. Recent experimental evidence suggests that Physalis extracts and their isolated constituents, exhibit potent antifibrotic effects by modulating key molecular pathways involved in hepatic stellate cell (HSC) activation, oxidative stress, and inflammatory signaling. Despite promising findings, these studies are dispersed across various experimental models, extraction methods, and outcome measures, making it difficult to draw comprehensive conclusions about their therapeutic potential. Therefore, this systematic review aims to critically synthesize and evaluate existing evidence on the antifibrotic and hepatoprotective effects of Physalis extracts and their bioactive compounds in liver fibrosis models. By summarizing current findings and identifying knowledge gaps, this review seeks to provide a scientific basis for future pharmacological development and potential clinical translation of Physalis-derived agents for liver fibrosis management.