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

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

doi:10.1186/s12906-016-1385-5

Abstract

Background 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.MethodsIn 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.ResultsSeven 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.ConclusionThese 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.Graphical abstractEstrogenic and cytotoxic potentials of compounds isolated from Millettia macrophylla Benth. (Fabaceae): towards a better understanding of its underlying mechanism Electronic supplementary materialThe online version of this article (doi:10.1186/s12906-016-1385-5) contains supplementary material, which is available to authorized users.

Highlights

Millettia macrophylla was previously reported to have estrogenic effects and to prevent postmenopausal osteoporosis in Wistar rats
As part of our continuous search of new phytoestrogens, we focused the study on Millettia macrophylla (Fabaceae), a plant growing in sub-Saharan Africa
Phytochemical analysis of M. macrophylla Identification of M. macrophylla isolates A total of 13 secondary metabolites were isolated from M. macrophylla stem barks extracts

Summary

Introduction

Millettia macrophylla was previously reported to have estrogenic effects and to prevent postmenopausal osteoporosis in Wistar rats. Chemotherapy and surgery remain the major treatments of this ailment side effects and the treatment expense represent two major difficulties for affected patients, especially those from Sub-Saharan Africans. These two factors make approximately 80 % of the population rely and use medicinal plants for their primary healthcare problems or as an alternative solution to cure diseases [3]. Natural estrogenic compounds include coumestans, isoflavonoids and flavonoids [11, 12] Since they are endowed with both estrogenic and antiestrogenic properties, these natural selective estrogen receptors modulators are promoted as a preventive alternative against estrogendependent cancers such as breast, ovarian, uterine and prostate cancers [13]

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