Obesity, a critical global health issue, is a major risk factor for metabolic syndrome. There is growing scientific interest in identifying natural, nutrient-rich legumes as safer and more sustainable alternatives for controlling obesity and its related disorders. This study aimed to elucidate the molecular mechanisms underlying the anti-obesity and anti-inflammatory properties of a methanolic extract of yard-long bean (Vigna unguiculata subsp. sesquipedalis) seeds in mice with high-fat diet (HFD)-induced obesity.

An integrated approach combining computational bioinformatics, network pharmacology, and animal experimentation was employed. Bioactive constituents were characterized using GC–MS, while compound–protein interactions were explored through network pharmacology. Biochemical analyses and real-time PCR were performed to confirm predicted molecular targets and pathways.

GC–MS analysis identified 61 phytoconstituents, with quercetin, kaempferol, luteolin, linolenic acid, and tocopherols highlighted as key candidates based on ADMET profiles, drug-likeness, and predicted oral bioavailability. Network pharmacology revealed that these compounds interact with 223 obesity-associated genes, including IL6, AKT1, SRC, EGFR, ESR1, PPARγ, PTGS2, MAPK3, MMP9, and GSK3B, primarily involving the TNFα, PPAR, arachidonic acid metabolism, and MAPK signaling pathways—indicating a multi-target therapeutic action. In vivo, the extract significantly lowered body weight gain, adipose tissue accumulation, hyperglycemia, and risks of hepatic and cardiac dysfunction in a dose-dependent manner. Gene expression analysis showed marked suppression of adipogenesis- and inflammation-related markers (PPARγ, HMOX1, Wdnm1-like, TNF-α, IL-6, MCP-1, COX-2) alongside upregulation of the browning marker UCP-1.

Yard-long bean seed extract exhibits potent anti-obesity and anti-inflammatory effects by targeting multiple metabolic and signaling pathways, including PPARγ signaling pathway, supporting its potential as a functional food or nutraceutical for the prevention and management of obesity and its complications.