Non-alcoholic fatty liver disease (NAFLD) is a prevalent metabolic disorder that has become a global health challenge. With the lack of effective FDA-approved treatments, alternative therapies are being explored. Astragaloside IV (AS-IV), a bio-active compound derived from the plant Astragalus membranaceus (Fisch. ex Bunge) (Fabaceae/Leguminosae), native to Inner Mongolia and Siberia, has shown significant therapeutic potential in NAFLD. This review discusses the pharmacological effects and molecular mechanisms of AS-IV, highlighting its role in improving insulin resistance, regulating lipid metabolism, reducing oxidative stress and modulating inflammation. AS-IV acts through key molecular pathways, such as AMPK, Nrf2 and SREBP-1c, to mitigate liver steatosis and inflammation. Additionally, AS-IV influences gut microbiota and bile acid metabolism, contributing to its therapeutic effects. Despite promising results from preclinical studies, clinical data supporting AS-IV’s efficacy in NAFLD treatment are limited. Future research should focus on clinical trials, pharmacokinetics, and the combination of AS-IV with other therapeutic agents to optimise its therapeutic potential and reduce side effects.
© 2025 Hui Wang, Yunqin Jiang, Shiyun Wang, Chanchan Lu, Lumin Tang, Tingting Gu, Shi Shu, published by Croatian Pharmaceutical Society
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