Investigation of the uterine modulating activities and mechanisms of Brachystegia eurycoma Harms (Leguminosae) methanol stem bark extract and fractions

Abstract

Dysfunctional labour (DL) is a major cause of maternal and neonatal deaths worldwide. The only clinically available drug is oxytocin which is about 50% effective. Therefore, the development of new effective drugs for DL is a necessity. The medicinal plant Brachystegia eurycoma Harms (synonym B. spiceaformis) is used for labour management in ethnomedicine. In the search for new lead compounds for DL therapy, the stem bark of B. eurycoma was subjected to bioactivity-guided fractionation procedures to elucidate its uterine-modulating activities and active compounds. B. eurycoma stem bark extract (BE) was fractionated via vacuum liquid chromatographic techniques. The fractionation process was guided by ex vivo uterine contractility assays on the mouse uterus, performed using spontaneous, oxytocin, and high KCl-induced contractility assays. Furthermore, the characterization of the chemical constituents was performed using nuclear magnetic resonance (NMR) and mass spectrometry (MS). BE produced dual effects on uterine contractility which was dependent on the reconstitution period. The freshly prepared crude extract (BEF) inhibited uterine contractility (IC50 amplitude = 0.8 ± 0.1 mg/ml; IC50 frequency = 1.4 ± 0.2 mg/ml). However, contractility was augmented when the reconstituted extract was stored for 24 h and beyond (BES) (EC50 amplitude = 0.2 ± 1.2 mg/ml; EC50 frequency = 0.91 ± 1.2 mg/ml). In addition, the compounds caffeine, genistein, and prunetin were identified from the potent BE fractions via the different spectroscopic and spectrometric tools. This study demonstrated a storage-dependent dual effect of BE where BEF induced inhibition and BES augmented uterine contractility. Findings from this study also suggest that caffeine and phytoestrogens contributed to the uterine-modulating activities of BE. Thus, further investigation of these compounds in combination and as separate lead compounds is required for DL therapeutic management.