Mechanism of lupenone improving pancreatic inflammation in type 2 diabetes and screening potential ingredients for Miao medicine

This study aimed to elucidate how lupenone from Miao medicine inhibits type 2 diabetes-associated pancreatic inflammation (T2DM&PI) and to screen the potential ingredients from Miao medicine using the core targets TLR4 and NF-κB-p65. Through network analysis, molecular docking, and animal experiments, a 'lupenone-target-disease' network was constructed, and 10 key targets (like BCL2, JUN, SRC, INS, ESR1, RELA), 939 biological processes, and 95 signalling pathways were identified. Furthermore, lupenone showed good affinity for the top 10 targets and downregulated the TLR4/TRAF6/NF-κB-p65 pathway in pancreas tissues of T2DM mice. Molecular docking identified 108 TLR4-targeting components (affinity< -7.5 kcal/mol) and 274 NF-κB-p65-targeting components (affinity< -8.5 kcal/mol). Lupenone ameliorates T2DM&PI by inhibiting the TLR4/TRAF6/NF-κB-p65 pathway. Notably, 'clear heat and detoxify' Miao medicine may contain abundant ingredients for T2DM&PI, which require further confirmation.