Probing the mechanism of the anti-diabetic potential of a terpenoid from Elephantopus scaber L., an Indian ethnomedicinal plant in STZ diabetic rats- In vivo and in silico analysis

ABSTRACT

Plants have always been an exemplary source of drugs and many of the currently available drugs have been derived directly or indirectly from them. Since ancient times, traditional medicines all over the world have advocated the use of plants to treat diabetes. Elephantopus scaber L. assumes significance because it has shown by us to possess high hypoglycemic effect and justifies the traditional claims of being anti-diabetic drug candidate. The terpenoid isolated from Elephantopus scaber L. demonstrated promising antihyperglycemic property with an increase in insulin levels but the mode of action had not been investigated. Since increased insulin levels are associated with β-cells of the pancreas, histological studies were undertaken to evaluate the effect of the compound on β-cells protection in streptozotocin induced diabetic rats. Streptozotocin is known to cause damage to β-cells and hence the protective and curative role of terpenoid was evaluated on the restoration of β-cells. The regeneration of damaged β-cells on the administration of the terpenoid is evident from histological and ultra-structural investigations. In histological observations, islets of extract-treated diabetic rats are seen to have numerous cells with normal histoarchitecture. Ultrastructural studies revealed β-cells of compound-treated diabetic rats to contain granulated secretory vesicles. The plant may act independently or synergistically to regenerate the damaged endocrine pancreas and thereby stimulation of insulin secretion in β-cells as revealed by LM and TEM. To further confirm the mode of action of the compound, in silico docking with target proteins like PPARγ, which plays a role in protecting β-cells from damage was undertaken. The docking analysis in the active sites of 2PRG was performed by Schrodinger program. The docking results showed good binding interactions of the ligand with the target at the very low energy level. In our in silico analysis, terpenoid isolated from E. scaber clearly demonstrated that it could improve the diabetic condition by increasing insulin secretion from remnant or regenerated pancreatic β-cells and could promote insulin sensitization and glucose uptake activities, which was a supporting evidence to the histological studies. Thus the terpenoid from E. scaber can be considered for developing into a potent antidiabetic drug.