Understanding the mechanism of Crassocephalum crepidiodes (Benth.) S. Moore leaf antifibrotic activity using in vivo and in silico methods

Approximately 30% of women of reproductive age are affected by uterine leiomyomas (fibroids). In women of reproductive age, these benign tumours have been associated with a higher risk of developing type II diabetes and infertility, which can lead to significant mental stress. Cytogenic abnormalities and somatic mutations-particularly in transcription factors such as GATA2 and FOXPI-are being considered as potential biomarkers for early detection and management. There is a pressing need for safer and more effective therapeutic options with fewer adverse effects. Therefore, this study evaluated the antioxidant, α-amylase, and α-glucosidase enzymes inhibitory and ameliorative effects of Crassocephalum crepidiodes on monosodium glutamate (MSG)-induced uterine leiomyoma in albino rats and proposed their mechanisms of action using an in silico approach. The NO radical scavenging efficacy of the control used, quercetin, is comparable to that of an aqueous extract of C. crepidiodes leaves. The extract's ability to chelate iron (Fe²⁺) is lower than quercetin, the used control. The extract's α-amylase inhibitory activity is lower than the control's. The IC₅₀ value for AChE inhibition by the extract was 0.113 ± 0.010 µg/mL, which is approximately 1.8-fold higher than that of the standard inhibitor, donepezil (0.061 ± 0.009 µg/mL), indicating considerable AChE inhibition. Similarly, the extract significantly inhibited MAO activity in a dose-dependent manner. Although the MSG-treated group and the C. crepidiodes-treated group had non-comparable levels of luteinizing hormone (LH) levels, the MSG-induced uterine leiomyoma rats also had noticeably higher levels of testosterone. The extract-treatment group's reduced levels of testosterone and oestradiol relative to the MSG-induced fibrotic group demonstrated that C. crepidiodes effectively corrected the fibrotic albino rats' hormonal abnormalities. C. crepidiodes extract's HPLC-identified components, chlorogenic acid and ellagic acid, demonstrated high binding profile and stability with GATA2 and FOXP1 targets, supporting the in vivo antifibrotic activity of this plant. Hence, C. crepidiodes may have intricate effects on the molecular pathways linked to uterine fibroids, such as re-establishing normal ovarian morphology, hormone balance, and insulin sensitivity.