Biochanin A enhances wound healing in diabetic rats: emphasis on antioxidant, anti-inflammatory, angiogenic and pro-collagen activities.

Diabetic wounds represent a serious complication, affecting ~ 25% of patients and may lead to amputation, with significant socioeconomic consequences. This study investigated the potential of biochanin A (BCA), a natural isoflavone, to enhance wound healing in a diabetic rat model. Diabetes was induced via streptozotocin. A full-thickness about ~ 1-cm dorsal wound was created, and animals were grouped into five groups: non-diabetic control, untreated diabetic, vehicle-treated diabetic, BCA-treated diabetic, and a positive control group. All respective treatments were applied topically once daily for 14 days. Wound closure was monitored periodically. On day 15, rats were sacrificed and tissue samples were collected for histological evaluation, immunohistochemistry, and biochemical analysis to assess oxidative stress, inflammation, angiogenesis marker, and collagen deposition. BCA treatment significantly accelerated wound contraction and improved healing rates compared to untreated diabetic controls. Histopathological examination using hematoxylin and eosin and staining by Masson's trichrome showed enhanced granulation tissue formation, re-epithelialization, and neovascularization. Mechanistically, BCA activated Nrf2 and NAD(P)H:NQO1, upregulated key antioxidant enzymes SOD and CAT, and reduced lipid peroxidation accumulation. It also suppressed immune-expression of pro-inflammatory markers. Furthermore, BCA treatment enhanced expression of critical angiogenic growth factors VEGF-A and PDGFR and enhanced collagen deposition as evidenced by increased immune-expression of TGF-β1 and mRNA expression of Col1A1. Our findings demonstrate that BCA promotes diabetic wound healing through a multi-targeted mechanism involving enhancement of the antioxidant system, attenuation of the inflammatory phase, and stimulation of angiogenesis and collagen deposition.