Unveiling the molecular mechanisms of adzuki bean ( Vigna angularis) derived bioactive phytochemicals in combating obesity

Obesity is a global chronic metabolic disorder, and our previous research studied the anti-obesity effect of the adzuki bean and identified some phytochemicals, including flavonoids and saponins. However, it is still unclear which phytochemical derived from adzuki bean play a crucial role in the anti-obesity effect and its mechanisms. This research is the first study to reveal the anti-obesity phytochemicals in adzuki bean and its molecular mechanisms. The active compounds of adzuki beans were identified from previous research of our research team and TCMSP database. A total of 13 active phytochemicals and 205 anti-obesity targets were identified. The protein-protein interaction, network analysis, gene ontology, and Kyoto Encyclopedia of Genes and Genomes enrichment analyses indicated that the Wnt signaling pathway, PI3K/Akt signaling pathway, and MAPK signaling pathway may be involved in anti-obesity effect of adzuki bean. Through PPI analysis, TNF, SRC, IL6, VEGFA, HRAS, and JUN were identified as core targets and further utilized for molecular docking. The molecular docking analysis shows that core active compounds can bind to core anti-obesity targets. Based on the above results, ADMET analysis, and further molecular simulation, vitexin-4 ''-O-glucoside has the highest potential for the anti-obesity effect and was further validated by Nile red staining and ORO staining in the in vitro adipocyte cell model. Furthermore, the vitexin-4 ''-O-glucoside achieves anti-obesity effect through regulating the Wnt/ (3-catenin signaling pathway and its downstream transcription factor C/EBP alpha and PPAR gamma. This may provide a solid foundation for the clinical application and further research of adzuki beans in treating obesity.