Dual Activation of GLP-1 and AMPK Pathways by a Multi-Botanical Formulation Improves Obesity and Metabolic Dysfunction in Experimental Models

Background: Obesity is a multifactorial metabolic disorder characterized by excessive adiposity, chronic low-grade inflammation, and dysregulated incretin and energy-sensing pathways, including glucagon-like peptide-1 (GLP-1) and AMP-activated protein kinase (AMPK). Methods: This in vitro and in vivo study evaluated the potential of select phytochemical candidates and botanical formulations to stimulate GLP-1 secretion and activate AMPK signaling. Results: Fourteen phytochemicals and six combinations were screened in human NCI-H716 enteroendocrine cells at 10–20 µg/mL to assess cytotoxicity and GLP-1 secretion. In human adipocytes, selected combinations reduced lipid accumulation and monocyte chemoattractant protein-1 (MCP-1) secretion. Among the tested formulations, combination #4, consisting of ginseng root extract, curcumin, white kidney bean extract, fenugreek extract, capsaicin, and bitter melon extract, significantly increased phosphorylated AMPK levels in vitro. In high-fat diet-induced obese mice, oral administration of combination 4 reduced body weight gain and white adipose tissue mass, improved metabolic biochemical parameters, restored leptin and MCP-1 levels toward normal values, increased GLP-1 level, and normalized GLP-1 receptor expression in subcutaneous adipose tissue. Conclusions: These preclinical findings demonstrate that this multi-component botanical formulation modulates GLP-1 secretion, AMPK phosphorylation, lipid accumulation, and inflammatory markers in cellular and murine models. These data provide a foundational rationale for its further evaluation as a non-toxic candidate for metabolic management.