Molecular Mechanisms of Wound Healing: The Role of Medicinal Plants
Merlin Esad, Ivica Dimov, Mariya Choneva, Mihaela Popova, Vesela Kokova, Elisaveta Apostolova, Anelia Bivolarska
Abstract
Wound healing is a tightly regulated biological process involving hemostasis, inflammation, proliferation, and tissue remodeling. When these phases are disrupted, wound repair can be delayed or become chronic. Key signaling pathways, including NF-κB, JAK/STAT, and MAPK, coordinate immune activation, cytokine expression, cell proliferation, and tissue repair. Medicinal plants and their bioactive compounds, such as flavonoids, alkaloids, tannins, and other phytoconstituents, have demonstrated significant anti-inflammatory, antioxidant, and immunomodulatory effects that modulate these pathways. Tannins contribute to repair through neutralization of reactive oxygen species (ROS), activation of antioxidant enzymes, and metal-chelating activity. Alkaloids, including tetrandrine, oxymatrine, and berberine, inhibit NF-κB signaling, thereby reducing pro-inflammatory cytokines such as IL-1β and TNF-α. Flavonoids regulate inflammatory mediators and enzymes, including COX and phospholipase A2, while also protecting against oxidative stress and stimulating fibroblast and keratinocyte proliferation-key steps in tissue regeneration. Collectively, these compounds accelerate wound closure by reducing oxidative stress and promoting cellular proliferation and migration. Thus, medicinal plants represent promising complementary approaches to wound management. Future research should focus on developing advanced drug delivery systems to enhance the stability, bioavailability, and targeted action of plant-derived compounds. Localized and biomaterial-based strategies show promise for sustained release at the wound site, and further preclinical and clinical studies are required to ensure their safety, reproducibility, and efficacy.