Molecular docking of glycogen synthase kinase3-β inhibitor oleanolic acid and its wound-healing activity in rats

Glycogen Synthase Kinase3-beta (GSK3-beta) is involved in energy metabolism, cell development, and body pattern formation, whose inhibition promotes wound healing through beta-catanin-dependent Wnt signaling pathway. Molecular Docking of oleanolic acid isolated from Methanolic extract of Grewia tiliaefolia bark to GSK3-beta was studied by Wnt signaling pathway. The activation domain of GSK3-beta docked with oleanolic acid showed the inhibition constant 1.55 x 10(-9) whereas, standard drug sulphathiazole showed inhibition constant of 9.27 x 10(-6). Both extract and isolated constituent were studied for their potency using excision, incision, and dead space wound models in rats. In oleanolic acid-treated animals (1 % w/w ointment cream base), epithelialization was faster with 96.82 % wound contraction on 16th post wounding day. Tensile strength of incision wound was significantly increased to 580.832.95 g after intraperitoneal administration of oleanolic acid (12 mg kg(-1) body weight). In dead space wound, a significant increase in weight, tensile strength, hydroxyproline content and increased collagenation of granuloma tissue was observed. Further in silico findings hypothesized that oleanolic acid may exert the healing activity by inhibiting GSK3-beta through beta-catanin-dependent Wnt signaling pathway.