In-silico Exploration of Phytoconstituents of Gymnema sylvestre as Potential Glucokinase Activators and DPP-IV Inhibitors for the future Synthesis of Silver Nanoparticles for the Treatment of Type 2 Diabetes Mellitus

Abstract

Diabetes has a large death toll worldwide, particularly as it falls into the ten leading causes of death. Type 2 diabetes mellitus (T2DM) occurs as the body becomes resistant to insulin and sugar accumulates in the blood. It has been observed that, dipeptidyl peptidase-IV (DPP-IV) inhibitors and glucokinase activators are known therapeutic agents to treat T2DM. Among the possible medicinal plants, Gymnema sylvestre (GyS) belongs to the Apocynaceae family and is traditionally used for the treatment of different diseases. This plant is also known as 'Gurmur' because it has a sugar reducing ability. GyS was known to be one of the main botanicals for the treatment of diabetes. Rendering to the studies described above, we have tried to investigate the natural DPP-IV inhibitors and potent glucokinase activators from the phytoconstituents of GyS. New drug candidates from the medicinal plant GyS have been reported as potent DPP-IV inhibitors and glucokinase activators. As a preliminary investigation, we have studied the effectiveness of phytoconstituents of GyS in T2DM through molecular docking as a proof of concept of synthesizing silver nanoparticles (for the treatment of T2DM) using extract of this plant. The present investigative research showed that diabetes mellitus has important values in the recognized compounds included in the present analysis. The nine compounds selected were evaluated on the basis of DPP-IV and glucokinase enzyme binding energy values and their drug properties. Except quercitol, all the selected compounds have exhibited very potent glucokinase activation potential than its native ligand. Gymnemasin A, lupeol, gymnemoside A, gymnemasaponin V and gymnemic acid I have shown excellent DPP-IV inhibitory potential. We are aiming to synthesis the silver nanoparticles of leaf extract of GyS for the treatment of T2DM. As a preliminary investigation, we have studied the effectiveness of phytoconstituents of GyS in T2DM through molecular docking as a proof of concept of synthesizing silver nanoparticles (for the treatment of T2DM) using extract of this plant. As a result of present investigation, it has been concluded that these compounds can be used to treat the T2DM and hence in future we will synthesize the silver nanoparticles of GyS extract for the treatment of T2DM.