Exploration of the Mechanism of Erchen Decoction in Ameliorating Obesity by Regulating LipidDeposition via the AMPK/SIRT1/PGC-1α Signaling Pathway

Introduction: Obesity, a global health crisis, necessitates innovative therapeutic strategies. Traditional Chinese Medicine (TCM), including Erchen Decoction (ECD), offers potential benefits; however, the molecular mechanisms underlying ECD's anti-obesity effects, particularly on lipid metabolism, remain unclear. This study investigates the mechanism by which ECD improves lipid metabolism through the AMPK/SIRT1/PGC-1α signaling pathway. Methods: AML-12 hepatocytes were cultured and divided into Control, Model (palmitic acid-induced lipid deposition), and treatment groups (ECD serum: 2%, 4%, 8%; orlistat: 10 μM). Cell viability, lipid accumulation, and triglyceride (TG) content were measured. Key lipid metabolism genes (p-AMPK/AMPK, SIRT1, PPARα, PGC-1α, Nrf2, TFAM) were evaluated using RT-qPCR, Western Blot, and immunofluorescence. Network pharmacology analysis identified ECD's targets and pathways. Results: The Model group showed increased lipid droplets and TG content, with reduced AMPK, SIRT1, PPARα, PGC-1α, Nrf2, and TFAM expression compared to Control. ECD treatment significantly decreased lipid droplets and TG content (at all doses), with the 4% dose being the most effective. ECD up-regulated all tested genes, confirmed by immunofluorescence (p-AMPK, SIRT1, PGC-1α). Network pharmacology highlighted the overlap between ECD and obesity pathways, with a particular emphasis on lipid metabolism. Discussion: ECD improves lipid metabolism in AML-12 hepatocytes by activating the AMPK/ SIRT1/PGC-1α pathway, consistent with prior research. The upregulation of Nrf2 and TFAM indicates enhanced mitochondrial function and resistance to oxidative stress. Limitations include the use of in vitro models; future studies should focus on clinical translation and dosage optimization. Conclusion: ECD regulates lipid metabolism via the AMPK/SIRT1/PGC-1α pathway, providing a scientific basis for its clinical use in obesity-related diseases. This study highlights ECD as a promising therapeutic strategy for improving lipid metabolism and reducing obesity-associated risks. .