Genistein as an Estrogen Receptor-Beta Selective Phytoestrogen: Molecular Docking Insights for Advanced Wound Healing Therapies

Wound healing is highly hormonal based and is stepwise process involving inflammation, proliferation, and remodeling .Estrogen is a key regulator having two receptor subtypes having various functions. Erα (Estrogen receptor alpha) promotes inflammatory signaling and Erβ (Estrogen receptor beta) helps extracellular matrix (ECM) deposition, epithelial regeneration, and also angiogenesis. Excessive ERα activity will prolong inflammation and hinder repair, whereas ERβ activation action is generally restorative. This difference makes ERβ-selective ligands suitable for therapeutic treatments, mainly in estrogen-deficient chronic wounds. SERMs have attained importance as they mimic estrogen but carry minimum systemic risks than other hormone therapy. Genistein, an isoflavone abundant in soy, is best candidate because of its receptor-biased activity. Twelve phytoestrogenic ligands were docked with ERα and ERβ using SwissDock to assess receptor selectivity. Genistein shows maximum affinity for ERβ (−8.09 kcal/mol), which forms hydrogen bonds with residues ARG346, GLU305,HSE475. ERα shows a weaker interaction (−7.80 kcal/mol), enhancing Erβ preference. Liquiritigenin and glycitein shows Erβ preference but less strongly. These findings concludes that genistein accelerates repair through angiogenesis and ECM remodeling by ER beta signaling over ER alpha. However, the direct use is limited due to its poor solubility, making clinical application of nanocarrier or hydrogel delivery systems preferable.