Obesity causes low-grade inflammation that results in dyslipidemia and insulin resistance. We evaluated the effect of puerarin on obesity and metabolic complications both in silico and in vivo and investigated the underlying immunological mechanisms. Twenty C57BL/6 mice were divided into four groups: normal chow, control (HFD), HFD + puerarin (PUE) 200 mg/kg, and HFD + atorvastatin (ATO) 10 mg/kg groups. We examined bodyweight, oral glucose tolerance test, serum insulin, oral fat tolerance test, serum lipids, and adipocyte size. We also analyzed the percentage of total, M1, and M2 adipose tissue macrophages (ATMs) and the expression of F4/80, tumor necrosis factor-α (TNF-α), C-C motif chemokine ligand 2 (CCL2), CCL4, CCL5, and C-X-C motif chemokine receptor 4. In silico, we identified the treatment-targeted genes of puerarin and simulated molecular docking with puerarin and TNF, M1, and M2 macrophages based on functionally enriched pathways. Puerarin did not significantly change bodyweight but significantly improved fat pad weight, adipocyte size, fat area in the liver, free fatty acids, triglycerides, total cholesterol, and HDL-cholesterol in vivo. In addition, puerarin significantly decreased the ATM population and TNF-α expression. Therefore, puerarin is a potential anti-obesity treatment based on its anti-inflammatory effects in adipose tissue.

Obesity represents chronic low-grade inflammation that precipitates type 2 diabetes, cardiovascular disease, and cancer. Berberine (BBR) has been reported to exert anti-obesity and anti-inflammatory benefits. We aimed to demonstrate the underlying immune-modulating mechanisms of anti-obesity effects of BBR. First, we performed in silico study to identify therapeutic targets, describe potential pathways, and simulate BBR docking at M1 and M2 adipose tissue macrophages (ATMs), tumor necrosis factor-α (TNF-α), C-C motif chemokine ligand 2 (CCL2), CCL4, CCL5, and C-X-C motif chemokine receptor 4 (CXCR4). Next, in vivo, we divided 20 C58BL/6 mice into four groups: normal chow, control (high fat diet (HFD)), HFD + BBR 100 mg/kg, and HFD + metformin (MET) 200 mg/kg. We evaluated body weight, organ weight, fat area in tissues, oral glucose and fat tolerance tests, HOMA-IR, serum lipids levels, population changes in ATMs, M1 and M2 subsets, and gene expression of TNF-α, CCL2, CCL3, CCL5, and CXCR4. BBR significantly reduced body weight, adipocyte size, fat deposition in the liver, HOMA-IR, triglycerides, free fatty acids, ATM infiltration, all assessed gene expression, and enhanced the CD206+ M2 ATMs population. In conclusion, BBR treats obesity and its associated metabolic dysfunctions, by modulating ATM recruitment and polarization via chemotaxis inhibition.