Research Progress and Prospects of Saponins in the Treatment of NAFLD: A Narrative Review.

Non-alcoholic fatty liver disease (NAFLD) represents a prevalent chronic hepatic disorder worldwide, with its incidence continuing to rise in recent years. At the core of its pathological progression lie multiple interconnected mechanisms, including dysregulated lipid metabolism (e.g., abnormal accumulation of triglycerides in hepatocytes), impaired insulin sensitivity (which exacerbates hepatic lipid deposition), excessive production of reactive oxygen species (ROS) leading to oxidative stress, and sustained low-grade chronic inflammation that further amplifies liver tissue damage. Saponins have emerged as a crucial research direction for NAFLD intervention due to their advantage of multi-target regulation. This review synthesizes the mode of action of commonly studied saponins, including triterpenoid saponins and steroidal saponins: they regulate lipid metabolism by inhibiting fatty acid synthesis; modulate the gut microbiota; scavenge reactive oxygen species (ROS); alleviate endoplasmic reticulum stress; exert anti-inflammatory effects by inhibiting inflammasomes; and simultaneously regulate autophagy, restrain the activation of hepatic stellate cells, and modulate the gut microbiota, thereby achieving anti-apoptotic and anti-hepatic fibrosis effects. In conclusion, saponins can synergistically intervene in NAFLD through multiple mechanisms with good safety, while low bioavailability constitutes the main bottleneck for their clinical translation. In the future, it is necessary to further optimize formulation processes to improve absorption efficiency and conduct high-quality clinical studies to verify their long-term efficacy and drug-drug interactions, thus providing a new possible direction for NAFLD treatment.