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.