Multitargeted antidiabetic intervention of phytocompounds of methanolic fruit extract of Cordia myxa L.: Integrated from in-silico and in-vivo studies

Abstract The current study aimed to investigate the multitargeted antidiabetic potential of the methanolic extract of C. myxa fruits (MECMF) through in-silico and in-vivo assessments. Chemical fingerprinting of the test extract was performed using LC–MS/MS, with authentication of the UNIFI scientific library database. Potent phytocompounds were screened out by using the protein ligand molecular docking against the multitargets (dipeptidyl peptidase-4 (DPP-4), α-amylase, and α-glycosidase) through assessments of binding energy and related parameters. Further validation of interactions with target proteins was examined by following the molecular dynamics simulations at 1ns with the standard conditions by calculations of RSMD, and hydrogen bond profiling. The assessments of molecular dynamic simulation showed significant interactions by the selected three complexes i.e ., DPP-4 -β-sitosterol, α-amylase-cordiaquinone C, and α-glycosidase-cordiaquinone G. ADMET revealed substantial drug likeness characteristics of the screened phytocompounds. Consequently, the nicotinamide–streptozotocin–induced type 2 diabetic rat model was utilized for biochemical and histological studies. The treatment of the test extract and standard drug (sitagliptin) showed alterations in HOMA indices, lipid metabolism, oxidative stress, and histology of the pancreas. Substantial improvements were revealed by the treatment of the test extract in the histoarchitectures of pancreases through reducing the degenerative changes. These kinds of alterations were followed by the ameliorated oxidative stress through significant improvements in the FRAP, GSH, and LPO. Collectively, it can be concluded that phytocompounds of the C. myxa have capabilities to interfere in glucose metabolism through a multitargeted approach. Further experimentation can be promoting the drug development practices for the therapeutics of diabetes.