Roles and mechanisms of Pueraria lobata radix in metabolic dysfunction-associated steatotic liver disease

The root of Pueraria montana var. lobata (Willd.) Ohwi, known as Pueraria lobata radix (PLR), is a medicinal and edible herb. In traditional Chinese medicine, PLR has historically been revered for its efficacy in "generating fluids to quench thirst" to treat metabolic disorders such as wasting-thirst syndrome (diabetes) and for its ability to alleviate alcohol intoxication. These traditional applications parallel the modern management of metabolic dysfunction and liver injury, providing an ethnopharmacological basis for its use in treating metabolic dysfunction-associated steatotic liver disease (MASLD).

This review aims to systematically summarize the bioactive components of PLR and their pharmacological mechanisms in the treatment of MASLD, and to discuss the current status of clinical applications and safety profiles.

Information regarding the application of PLR in MASLD was systematically retrieved from electronic databases including PubMed, Embase, Cochrane Library, Web of Science, and CNKI. The literature search covered the period from the inception of these databases to May 1, 2026. Key terms included "Pueraria lobata radix," "Puerarin," "MASLD," and relevant pathophysiological targets.

PLR contains diverse bioactive components, primarily isoflavones (e.g., puerarin, daidzein, genistein, and formononetin), polysaccharides, peptides, and resistant starch. Pharmacological evidence indicates that PLR combats MASLD through a multi-target and multi-pathway network. It regulates hepatic lipid metabolism via the AMPK, PPARs, and mTOR pathways; improves insulin resistance through the PI3K/Akt signaling cascade; and alleviates inflammation by inhibiting the JNK/p38 MAPK and NF-κB pathways. Furthermore, PLR exerts antioxidant effects via the Nrf2/ARE axis and mitochondrial quality control (mitophagy) and alleviates liver fibrosis by suppressing hepatic stellate cell activation. Notably, PLR modulates the gut-liver axis by reshaping gut microbiota composition, repairing the intestinal barrier, and regulating bile acid metabolism. While PLR demonstrates a favorable safety profile as an edible herb, caution regarding the usage of puerarin injection is highlighted due to potential adverse reactions.

Existing evidence indicates that multiple active components of PLR can exert anti-MASLD effects by regulating lipid metabolism, inflammation, insulin resistance, oxidative stress, gut microbiota, and fibrogenesis. These findings suggest that PLR and its active components possess the potential to serve as or be developed into therapeutic agents for MASLD. However, current evidence is primarily derived from preclinical animal models or in vitro experiments, and direct evidence from human studies is still lacking. In the future, conducting large-scale, double-blind, randomized controlled trials is essential to verify the efficacy and safety of PLR and its active components for MASLD.