Estrogenic and cytotoxic potentials of compounds isolated from Millettia macrophylla Benth (Fabaceae): towards a better understanding of its underlying mechanisms

Estrogenic and cytotoxic potentials of compounds isolated from Millettia macrophylla Benth (Fabaceae): towards a better understanding of its underlying mechanisms

BMC Complementary Medicine and Therapies, October 2016

27784319

Stéphane Zingue, Job Tchoumtchoua, Dieudonnée Mireille Ntsa, Louis Pergaud Sandjo, Julia Cisilotto, Chantal Beatrice Magne Nde, Evelyn Winter, Charline Florence Awounfack, Derek Tantoh Ndinteh, Colin Clyne, Dieudonné Njamen, Maria Halabalaki, Tânia Beatriz Creczynski-Pasa

Millettia macrophylla was previously reported to have estrogenic effects and to prevent postmenopausal osteoporosis in Wistar rats. So, the study deals with the identification of its secondary metabolites and the evaluation of their estrogenicity and cytotoxicity toward tumoural cells. Thus, 13 known compounds were obtained from successive chromatographic columns and identified by NMR data compared to those previously reported. In vitro estrogenicity of the isolates and the phenolic fraction (PF) of M. macrophylla were performed by E-screen and reporter gene assays, while their cytotoxicity was evaluated by Alamar Blue (resazurin) assay. A 3-days uterotrophic assay and the ability of PF to alleviate hot flushes in ovariectomized adult rats were tested in vivo. Seven of the 13 secondary metabolites turned to be estrogenic. Only two exhibited cytotoxic effects on MCF-7 and MDA-MB-231 with CC50 values of 110 μM and 160 μM, respectively. PF induced a significant (p < 0.01) MCF-7 cells proliferation and transactivated both ERα and ERβ in the reported gene assay at 10(-2) μg/mL. In vivo, PF acted more efficiently than the methanol crude extract, resulting to a significant (p < 0.01) increase in the uterine wet weight, uterine protein level, uterine and vaginal epithelial height at the dose of 10 mg/kg BW. In addition, PF reduced the average duration and frequency of hot flushes induced in rat. These aforementioned results indicate that PF is a good candidate for the preparation of an improved traditional medicine able to alleviate some menopausal complaints such as vaginal dryness and hot flushes. Estrogenic and cytotoxic potentials of compounds isolated from Millettia macrophylla Benth. (Fabaceae): towards a better understanding of its underlying mechanism.