An integrative <i>in silico</i> and <i>in vitro</i> approach to target uterine fibroids using natural compounds

Uterine fibroids (UFs) are uterine tumours in fertile-age females, impairing fertility and quality of life. Current treatments are predominantly surgical, necessitating safer non-invasive alternatives. This study investigated the therapeutic potential of Gloriosa superba (Langali), Capparis spinosa (Himsra), and Leonotis nepetefolia (Granthiparni) for UF therapy. The plants were characterised using WHO-recommended physicochemical parameters. Methanolic extracts selectively inhibited fibroid cells’ viability with IC50 values of 570.05, 318.45, and 303.65 µg/mL for Langali (root), Himsra (whole plant), and Granthiparni (root), respectively, while 675.7 µg/mL, 499.55 µg/mL, and 698.9 µg/mL, respectively, for normal myometrium cells, indicating selective cytotoxicity. Liquid chromatography-mass spectrometry identified phytochemicals were docked against oestrogen and progesterone receptors. Twenty complexes showed binding energies ≥5 kcal/mol, with quercetin and cholorogenic acid demonstrating the highest binding affinities. Simulation study confirmed five stable complexes. Drug-likeness and pharmacokinetics studies supported safety, suggesting these plants as promising candidates for non-surgical UF therapy, warranting further investigations.