Paper Title
AGERATUM CONYZOIDES LINN. EXTRACT PROMOTES IN VITRO AND IN VIVO WOUND HEALING VIA EPIGENETIC MODULATION OF CELL SURVIVAL PATHWAYS

Abstract
Effective wound healing is imperative in clinical medicine, and the utilization of plant-based remedies stands as a significant facet of healthcare. Wound repair, a natural physiological process, involves the regeneration and restoration of dermal and epidermal tissues. Recent concerns regarding the adverse effects and the development of antibiotic resistance have shifted attention towards alternative treatments. Ageratum conyzoides (AC) has emerged as a promising candidate in treating various skin ailments, including burns and infected wounds. This study delves into elucidating the molecular mechanisms underlying AC's wound healing properties. Our investigation reveals that AC extract enhances the proliferation, migration, and invasion of HDFa cells in vitro. Moreover, AC induces migratory, invasive, and tube-forming capabilities of HUVECs in vitro, along with stimulating neo-vascularization in matrigel plugs in vivo. AC treatment correlates with increased micro-vessel density, as evidenced by the upregulation of CD31, a neovascular marker. Mechanistically, AC's pro-fibrotic and pro-angiogenic effects are associated with decreased HDACs activity and increased acetylation, thereby upregulating the FAK/AKT/mTOR signaling pathway in skin fibroblasts. Notably, AC treatment induces phosphorylation of FAK, activating the AKT/mTOR pathway and enhancing MMP-9 activity. Furthermore, AC treatment accelerates wound contraction and reduces epithelialization time in BALB/c mice and Wistar rats. AC also augments the tensile strength of incision wounds in rats, surpassing that of standard ointments. Collectively, our findings suggest that AC facilitates wound healing, potentially through the epigenetically-regulated FAK/AKT/mTOR signaling pathway. Keywords - Ageratum Conyzoides, Wound Healing, Angiogenesis, Epigenetics.