Investigation of the Mechanism of Action of Liu Miao San in the Treatment of Lipid Metabolism Disorders on the basis of Network Analysis and Dynamic Ultrasound

Introduction: Lipid metabolism disorders are a critical global health issue. Liu Miao San (LMS), a traditional Chinese medicine (TCM) formula, has demonstrated clinical efficacy against these disorders; however, its underlying mechanism remains unclear. Methods: Network analysis was performed to predict LMS targets using the TCMSP and ETCM databases, followed by protein–protein interaction (PPI) network construction and GO/KEGG enrichment analyses. These predictions were validated in vitro using oleic acid-stimulated HepG2 cells by assessing lipid accumulation (Oil Red O staining, TG/TC measurements) and SREBP1/PPARγ localization via immunofluorescence. In vivo, high-fat diet (HFD)-induced rat models were used. Rats underwent dynamic ultrasound assessments, plasma and liver biochemical analyses (TG, TC, LDL-C, HDL-C, ALT, AST, TNF-α, IL-6), H&E staining, and liver immunofluorescence. Results: Network analysis identified SREBP1 and PPARγ as core targets. In vitro, LMS reduced lipid accumulation, decreased TG/TC levels, inhibited SREBP1 nuclear translocation, and promoted PPARγ nuclear translocation. In vivo, LMS alleviated HFD-induced lipid disorders, improved liver histopathology, reduced plasma TG/TC/LDL-C/ALT/AST and hepatic TG/TC/TNF-α/IL-6 levels, and normalized ultrasound parameters (e.g., liver volume and echogenicity). Immunofluorescence further confirmed SREBP1 inhibition and PPARγ activation in liver tissue. Discussion: LMS ameliorates lipid metabolism disorders through a dual regulatory mechanism: suppressing SREBP1 (reducing fatty acid and cholesterol synthesis) and activating PPARγ (promoting cholesterol efflux and exerting anti-inflammatory effects). This multitarget action addresses both hepatic and systemic lipid dysregulation. Conclusion: LMS exerts therapeutic effects via SREBP1/PPARγ modulation, supporting its clinical application in TCM and providing a methodological framework for mechanistic studies of complex herbal formulations.