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

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.

Cytotoxicity of the methanol extracts of Elephantopus mollis, Kalanchoe crenata and 4 other Cameroonian medicinal plants towards human carcinoma cells

“…This plant was moderately active against HepG2 cells, providing additional information on the anticancer activity of the plant. The poor cytotoxic effects of compounds and phenolic fractions of M. macrophylla towards breast cancer cells MCF-7 and MDA-MB-231, was reported [26]. Data obtained herein are in accordance with this previous study, as a moderate effect of MML was obtained in MCF-7 cells.…”

Lupeol, the major compound of the dichloromethane extract of Millettia macrophylla Benth (Fabaceae), displays estrogenic effects in ovariectomized rats

“…Triterpenoids of M . macrophylla DCM extract were isolated as previously reported (Zingue et al, ). Briefly, 8 g of DCM extract was chromatographed using a normal phase medium pressure liquid chromatography (BÜCHI Labortechnik AG) conditioned in a column with metal sheath glass (36 × 460 mm), adapted to the pressure of work (15 bar).…”

“…Twenty‐four hours after the last administration, animals were euthanized by decapitation. The relative uterine wet weight, uterine and vaginal epithelial heights, and differentiation of the mammary gland were assessed as described before by Zingue et al () and Zingue et al ().…”

Application of ultra‐performance liquid chromatography coupled with quadrupole time‐of‐flight mass spectrometry in identification of three isoflavone glycosides and their corresponding metabolites

“…Isoflavones, the secondary metabolites of herbal medicine, possess a variety of bioactivities such as antitumor, anti‐inflammatory, antioxidative, antiviral, antibacterial, and estrogenic effects . Recently, metabolites of isoflavones in the human body have aroused great interest due to the potential higher bioactivities, which became one of the most efficient ways for drug discovery . The intestinal flora in the gastrointestinal tract exert an important influence on the in vivo biotransformation of the components in phytomedicines .…”

“…Furthermore, the proposed metabolic pathways will be helpful for understanding the in vivo metabolic process of isoflavone.Recently, metabolites of isoflavones in the human body have aroused great interest due to the potential higher bioactivities, which became one of the most efficient ways for drug discovery. [18][19][20] The intestinal flora in the gastrointestinal tract exert an important influence on the in vivo biotransformation of the components in phytomedicines. 21 Previous studies found that the intestinal flora participated in the metabolism of flavones 22,23 and phenolic acids, 24 in which a deconjugating enzyme in bacteria played an important role on the biotransformation of parent compounds to new metabolites with more bioactivities.…”