A Systematic Review On ERK/MAPK Signaling Circuit As The Critical Regulator In Chronic Wound Healing: Phytochemicals As Possible Modulators?

INTRODUCTION: Wound healing is an important process in tissue regeneration and repair, during which events such as cell movement, proliferation, and tissue remodeling are keyfactor. Several pathological conditions, such as diabetes, hinder wound-healing processes. Mechanistically, healing processes are governed by many signaling pathways, which also influence scar formation; the ERK/MAPK pathway is a principal regulator of both wound healing and scar formation. Given the prevalence of chronic wounds worldwide, understanding this pathway is crucial for developing better treatment strategies. MATERIALS AND METHODS: Recent literature on the role of the ERK/MAPK pathway in healing chronic wounds, particularly in tissue repair and scar formation, was critically reviewed, exploring public databases and following the PRISMA approach. The findings on decoding the role of ERK pathways in wound healing, especially chronic wounds in diabetes, and screening phytomedicines for targeting the ERK/MAPK cascade are presented. RESULTS: The ERK/MAPK pathway controls the major stages of wound healing, viz., inflammation, cell migration, proliferation, and collagen deposition. DISCUSSION: Studies suggest that natural remedies, including extracts such as lemongrass, aloe vera and phytochemicals like citral, aloesin, catechin, can effectively modulate ERK signaling to shift the wound toward healing rather than scar formation. Although some progress has been made, further studies are needed to elucidate the diverse functions of ERK isoforms fully and to develop therapies with greater precision. CONCLUSION: ERK/MAPK-targeted phytotherapy is a useful intervention strategy that appears to facilitate healing of chronic wounds associated with life-threatening diseases.