Multi-omics characterization of glucose-lipid metabolic remodeling associated with Gymnema sylvestre (Retz.) R.Br. ex Sm. treatment in a type 2 diabetic mouse model

Ethnopharmacological relevance: Gymnema sylvestre (Retz.) R.Br. ex Sm. is a traditional herb widely used in Indian and Chinese ethnomedicine for diabetes and obesity management. Although its hypoglycemic and hypolipidemic effects have been extensively reported, a system-level understanding of how G. sylvestre modulates glucose-lipid metabolism has not been fully elucidated.

Aim of the study: The study aimed to explore metabolic alterations associated with G. sylvestre intervention in type 2 diabetes mellitus using an integrated multi-omics strategy.

Materials and methods: A type 2 diabetic mouse model was induced using a high-fat diet plus streptozotocin. Mice received graded doses of G. sylvestre extract for six weeks. Metabolic parameters, oxidative stress indices, and liver histopathology were assessed. Proteomic and metabolomic profiling coupled with integrative bioinformatics identified pathway-level metabolic alterations related to G. sylvestre treatment, with selected targets further examined by Western blot analysis.

Results: G. sylvestre treatment significantly improved glycemic control and lipid profiles, as shown by decreased fasting blood glucose, total Cholesterol, triglycerides, and low-density lipoprotein Cholesterol, along with enhanced Insulin sensitivity and hepatic glycogen storage. Integrated multi-omics analysis revealed coordinated alterations in 160 proteins and 43 metabolites, predominantly associated with glucose-lipid metabolism, including energy homeostasis and lipid metabolic regulation-associated pathways. Five proteins associated with lipid and energy metabolism were identified, including fatty acid synthase (FAS), carnitine palmitoyltransferase 1A (CPT1A), Acetyl-CoA Carboxylase alpha (ACACA), fatty acid-binding protein 5 (FABP5), and 1-acylglycerol-3-phosphate O-acyltransferase 3 (AGPAT3), together with metabolites involved in linoleic acid and glycerophospholipid metabolism, were identified as representative molecular features associated with G. sylvestre treatment.

Conclusion: This study provides integrative multi-omics evidence of coordinated glucose-lipid metabolic remodeling associated with G. sylvestre treatment in type 2 diabetes mellitus. By combining ethnopharmacological context with integrated multi-omics analyses, the results offer scientific support for the traditional application of G. sylvestre in metabolic disorder management.