Lupeol from Crateva adansonii DC Exhibits Promising Enzymes Inhibition: Play a Crucial Role in Inflammation and Diabetes

Abstract

Enzyme inhibitor from natural origin without any side effects and multi diseases target provide more advantageous over commercial drugs. In present study phytocompound lupeol was isolated from Indian traditional medicinal plant Crateva adansonii leave extracts and its possible applications for treating diabetes and inflammation diseases. Single major peak in HPLC profiling and FTIR functional group analysis of lupeol fraction (LF) confirmed the presence of phytocompound lupeol in LF. LF obtained from chloroform leave extract of Crateva adansonii had most prominent inhibitory activity on alpha-amylase and alpha glucosidase with IC50 values 16.31 µg/mL and 41.25 µg/mL respectively. LF exhibit superior COX-2 enzyme (91.36%) inhibition potential among all tested samples whereas LF exhibit equipotent (81.38%) MPO enzyme inhibitory potential compared with celecoxib standard drug (86.19%). In silico validation reveals that lupeol exhibit least docking score with excellent binding affinities of -9.2, -7.6, -10.0 -8.2 Kcal/mol with COX-2, myeloperoxidase, α-amylase and α-glucosidase inflammatory molecular target enzymes respectively than inflammatory (celecoxib) and diabetic (acarbose) reference standard drugs. Further in silico molecular dynamics simulation analysis revealed that Lupeol-COX-2 RMSD (root mean square deviation) plot showed that both COX-2 and Lupeol are stable after 20 NS at 9.0 Å for ligand and 3.2 Å for protein. Lupeol-α amylase complex showed good level of interaction throughout the simulation when compared with reference standard drug acarbose. Present study findings suggests that lupeol from Crateva adansonii plant could be incorporated in medicinal formulations intended for treatment of chronic inflammation and diabetic disorders.