Abstract
BACKGROUND: Metabolic dysfunction associated steatotic liver disease (MASLD) is a pressing global health issue with limited treatment options. Chinese sweet leaf tea (CSLT), rich in polyphenols, shows promise in addressing MASLD due to its anti-inflammatory, obesity-reducing, and metabolic-regulating properties. This study aimed to explore the therapeutic potential of CSLT polyphenols for MASLD treatment. METHODS: A comprehensive approach combining bioinformatics, network pharmacology, molecular docking, high-throughput sequencing, and experimental validation was employed. CSLT extracts were screened for active compounds, and potential targets associated with MASLD were predicted. A protein-protein interaction network was constructed to identify key regulators of lipid metabolism. Molecular docking studies validated interactions between core polyphenols and MASLD-related targets. In vitro studies using HepG2 cells and in vivo studies in a high-fat diet-induced rat model were conducted to assess the efficacy of polyphenol-rich CSLT extract (PE-CSLT) in ameliorating MASLD symptoms. RESULTS: A total of Eighty-two chemical constituents were initially identified in CSLT. Twenty-six active compounds were screened in CSLT extracts, targeting one hundred and six proteins related to twenty MASLD-associated genes. PE-CSLT demonstrated significant efficacy in reducing body weight gain, serum lipid levels, and liver fat accumulation in MASLD rats. Gene expression analysis revealed modulation of key metabolic regulators, including SREBP1, ACACA, AMPK, and PPARα. Molecular docking confirmed strong binding of eleven PE-CSLT components to these targets. Our findings highlight the therapeutic potential of PE-CSLT for MASLD, providing a scientific basis for its development as a novel drug. CONCLUSION: This study underscores the promise of natural products in modern medicinal practices and emphasizes the need for further clinical evaluation of PE-CSLT in MASLD management. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s41065-025-00504-6.