Comprehensive phytochemical mapping and biomedical evaluation of Lawsonia inermis L: a potential natural treatment for diabetic foot ulcers with wound healing and antimicrobial effects.

Diabetic foot ulcers (DFUs) are diagnosed in several million patients annually. The risk of death and amputation increases with the prevalence of associated multidrug-resistant infections. Lawsonia inermis L., commonly known as henna, is a plant species belonging to the family Lythraceae J.St.-Hil. For decades, it has been used to treat foot wounds and for other medical and cosmetic purposes. Various henna plant extracts were prepared, and 107 pus samples were collected to isolate multidrug-resistant bacteria and assess antibiotic susceptibility. A quantitative investigation of phenolic compounds in the bioactive ethanolic extract of L. inermis was conducted, along with a detailed characterization of its chemical composition using UPLC-MS/MS analysis in conjunction with the Global Natural Products Social Molecular Network (GNPS). An in vivo study was conducted to evaluate the efficacy of henna extract in treating infected diabetic wounds in rats, alongside an assessment of the gene expression of inflammatory biomarkers. The phytochemical study identified 93 chemicals, predominantly phenolic acids and flavonoids. Topical application of henna extract to infected diabetic wounds significantly enhanced healing, downregulated tumor necrosis factor-alpha (TNF-α) and Caspase-3 encoding genes, and upregulated the expression of transforming growth factor beta (TGF-β), interleukin-10 (IL-10), and vascular endothelial growth factor B (VEGF-B) encoding genes. Histopathological examination showed that henna extract-treated diabetic lesions developed mature epidermis, keratin, and basal cell layers after 15 days. The ethanolic henna extract is an effective natural treatment for DFUs, demonstrating wound healing and antimicrobial effects.