Identification of Natural Product Lead molecules as Potential Modulators of Wound Healing and Elucidation of the underlying Molecular Mechanisms
Wound healing is the result of a complex interplay between various cell types wherein macrophages and fibroblasts play a crucial role during various phases of the process. The different phases include hemostasis, inflammation, cellular migration, proliferation, wound contraction and remodeling. Both macrophage and fibroblast act as stimulators for several different cell types by producing various signaling factors like Platelet-Derived Growth Factor (PDGF), Transforming Growth Factor beta (TGF-ß), Fibroblast growth factor (FGF), Nitric Oxide (NO), Cytokines and Matrix Metalloproteinases (MMP). The aim of this project is to isolate, identify and characterize Natural Product lead molecules as novel modulators of wound healing. Our studies have implicated a role for Nitric Oxide (NO) and Matrix Metalloproteinases (MMPs) in the wound healing process. Current studies are focused on establishing the molecular mechanisms involved in these processes by such natural products. Our study with Ecdysterone convincingly demonstrated enhanced wound healing by increasing cell proliferation in a nitric oxide dependent manner.This study further demonstrated that Ecdysterone plays a role in cell migration by facilitating actin cytoskeletal re-arrangement.