Metabolic and anti-inflammatory effects of Gymnema sylvestre leaf extract in high-fat diet/streptozotocin- induced type 2 diabetic rats: evidence from metabolic profiling, gene expression, and network pharmacology

<title>Abstract</title> <p> Purpose Obesity and diabetes-induced metabolic dysfunctions are growing global concerns and are often linked to dysfunction of fatty acid metabolism. <italic>Gymnema sylvestre</italic> is a traditionally used medicinal plant in India and touted to be beneficial for such conditions. However, its impact on lipid metabolism-related gene expression and chronic adipose tissue inflammation remains unexplored. This study aims to investigate effects of <italic>G. sylvestre</italic> leaf extract on lipid metabolism-related gene expression and chronic adipose tissue inflammation in a rat model of type 2 diabetes mellitus (T2DM). Methods Obesity and adipose tissue dysfunction were induced by feeding high-fat diet (HFD) for 4 months in Wistar rats. This was followed by induction of pancreatic β-cell damage and T2DM in the rats by single intraperitoneal injection of Streptozotocin (STZ). The therapeutic efficacy of <italic>G. sylvestre</italic> leaf extract in regulating lipid metabolism-related gene expression, markers of chronic adipose tissue inflammation, and lipid metabolism was assessed and statistical analysis was done for analyzing groups. Results <italic>G. sylvestre</italic> leaf extract exhibited anti-hyperglycemic and anti-hypertriglyceridemic effects. The extract significantly downregulated expression of lipogenic genes, viz., ELOVL6 and CCL2. Treatment with <italic>G. sylvestre</italic> leaf extract also reduced markers of chronic adipose tissue inflammation such as inflammatory cytokines (TNFα and IL6) and anthropometrical parameters (body mass index), besides regulating thyroid function and lipid profile. Conclusions The findings of study provide scientific evidence that <italic>G. sylvestre</italic> leaf extract is a promising natural remedy as well as serve as potential therapeutic intervention for amelioration of adipose tissue dysfunction and related metabolic disorders in obese T2DM rats. </p>