Abstract
BACKGROUND: Diabetes mellitus is a prevalent endocrine condition. We aimed to investigate the anti-diabetic effects of 3-hydroxybakuchiol (HYD) by exploring its potential targets and molecular mechanisms through bioinformatics analysis and cell experiments. METHODS: We performed an extensive search and screening of HYD and its potential targets for diabetes mellitus across various databases. Enrichment analyses were conducted using the ClusterProfiler package. PPI networks of the identified genes were constructed using STRING, and topological analysis was performed to identify core targets. The results were further confirmed through molecular docking. To validate the findings of our bioinformatics analysis, we conducted cell experiments using insulin resistance-induced HepG2 cells and C2C12 cells. RESULTS: We discovered 260 common targets of HYD and diabetes mellitus, which were primarily related to the MAPK signaling pathway, PI3K-Akt signaling pathway, and endocrine resistance. A topological analysis of the PPI network identified four core targets (HSP90AA1, AKT1, SRC, and MAPK1). Molecular docking studies further confirmed the strong binding ability between HYD and these core targets. In cell experiments, we observed that HYD enhanced glucose uptake and suppressed gluconeogenesis in HepG2 cells and C2C12 cells. This resulted in an improvement in glucose metabolism, potentially through the regulation of the PI3K-Akt pathway. CONCLUSIONS: This study provides valuable insights into the pharmacological effects of HYD on diabetes mellitus, suggesting its potential as a promising treatment option for the disease.