Exploring the mechanism of Pueraria lobata (Willd.) Ohwi in the regulation of obesity.

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE Pueraria lobata (Willd.) Ohwi is a traditional medicinal and edible homologous plant rich in flavonoids, triterpenes, saponins, polysaccharides and other chemical components. At present, studies have shown that Pueraria lobata radix (PR) has the effect of lowering blood sugar, improving insulin sensitivity and inhibiting obesity. However, the specific mechanism of PR inhibits obesity is still unclear, and there are few researches on the anti-obesity effect of PR through the combination of network pharmacology and experiment. AIM OF THE STUDY Pharmacology, molecular docking technology and experimental verification through the network, revealing the PR the material basis of obesity and the potential mechanism. METHODS AND RESULTS: The present study used network pharmacology techniques to investigate the therapeutic effect and mechanism of action of PR. Through relevant databases, a total of 6 main chemical components and 257 potential targets were screened. Protein interaction analysis shows that AKT1, AKR1B1, PPARG, MMP9, TNF, TP53, BAD, and BCL2 are core targets. Enrichment analysis shows that the pathway of PR in preventing obesity involves the cancer signaling pathway and the PI3K-Akt signaling pathway, which may be the main pathways of action. Further molecular docking verification indicates that its core target exhibits good binding activity with 4 compounds formononectin, purerin, 7,8,4 '- trihydroxide and daidzein. Using the ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS) technology to detected and confirmed these main compounds. Cell experiment results revealed that puerarin inhibits cell proliferation and differentiation in a concentration dependent manner, significantly promoting cell apoptosis and affecting cell migration. Animal experiments have shown that puerarin reduces food intake and weight gain in mice. It was found that puerarin can upregulate HDL and downregulate TC, TG, and LDL blood biochemical indicators. Western blot results showed that puerarin significantly inhibited the expression of AKT1, AKR1B1, MMP9, TNF, TP53, BCL2, PPARG, and significantly increased the expression of BAD protein at both cellular and animal levels. CONCLUSION: The present study established a method for measuring PR content and predicted its active ingredients and their mechanisms of action in the treatment of obesity, providing a theoretical basis for further research.