Effects and molecular mechanisms of the combinationof Andrographis paniculata and Anredera cordifolia asan insulin sensitizer: in vitro, network pharmacology,molecular docking, and dynamics studies

Due to the complex mechanism of insulin resistance (IR), multi-component herbal medicines might be an alternative approach in the treatment of IR-related diseases, such as type 2 diabetes mellitus (T2DM). Andrographis paniculata (AP) and Anredera cordifolia (AC) have been reported to have anti-diabetic effects. However, their effect and mechanism of action in a mixed formula (FAPAC), especially as an insulin sensitizer have not been reported. Therefore, in vitro studies were performed to investigate the effect of FAPAC, and the molecular mechanisms were predicted by in silico studies through network pharmacology, molecular docking, and dynamics simulations. In vitro studies demonstrated that FAPAC at 2 mg/mL was comparable to metformin in increasing glucose uptake in IR-HepG2 cells. KEGG analysis revealed that IR was the top pathway and predicted that FAPAC acts as an insulin-sensitizing agent by inhibiting three main targets: IKBKB, PRKCD, and PTPN1. Consensus docking suggested 7-Omethyl wogonin, ninandrographolide, and 3-O-b-D-glucopyranosyl andrographolide as the potent inhibitors for IKBKB, PRKCD, and PTPN1, respectively. Furthermore, molecular dynamics confirmed that the potential compounds remained in the binding pocket throughout the simulation and had a good affinity toward their respective targets, comparable to native ligands.