Elucidation of Underlying Mechanisms by Which<i>Millettia macrophylla</i>Benth Induces Its Estrogenic Activity

Zingue, Stéphane; Nde, Chantal Beatrice Magne; Clyne, Colin; Njamen, Dieudonné

doi:10.1155/2014/763781

Cited by 5 publications

(6 citation statements)

References 29 publications

(21 reference statements)

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“…In order to contribute to a better understanding of the previous reported estrogenic/antiestrogenic properties of M. macrophylla [ 18 – 20 ], its major components were isolated. As striking observation, it was noted that most of these compounds belonging to the flavonoids group, specifically, isoflavone, pterocarpan and coumestan subgroups, which are well known as phytoestrogens.…”

Section: Discussionmentioning

confidence: 99%

“…Twenty-four hours after the last administration, animals were euthanized by decapitation. The uterine wet weight, total protein levels in uterine, uterine and vaginal epithelial heights and mammary gland were assessed as described before by Zingue et al [ 20 ].…”

Section: Methodsmentioning

confidence: 99%

“…Our previous work showed that M. macrophylla dichloromethane (DCM) and methanol (MeOH) extracts have estrogen-like effects on estrogen target organs of ovariectomized Wistar rats and prevent postmenopausal osteoporosis [ 18 , 19 ]. In addition the estrogen-like effects of these extracts were inhibited in vitro and in vivo by the pure ER antagonist ICI 182, 780 (Fulvestrant), indicating that their effects were primarily mediated through ERs [ 20 ]. These findings suggest the presence of estrogenic/antiestrogenic compounds in M. macrophylla helpful for the treatment of estrogen-dependent cancers, since two thirds of newly diagnosed invasive breast tumors are estrogen-dependent [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

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

Zingue

Tchoumtchoua

Ntsa

et al. 2016

BMC Complement Altern Med

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Zingue

Tchoumtchoua

Ntsa

et al. 2016

BMC Complement Altern Med

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“…M. thonningii is known to treat dysentery, constipation, and diarrhea while M. carulea has anti-inflammatory effects [8,9]. M. macrophylla is also used to relieve menopausal symptoms [10].…”

Section: Introductionmentioning

confidence: 99%

Isoflavones Isolated from the Seeds of Millettia ferruginea Induced Apoptotic Cell Death in Human Ovarian Cancer Cells

et al. 2020

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The seeds of Millettia ferruginea are used in fishing, pesticides, and folk medicine in Ethiopia. Here, the anti-cancer effects of isoflavones isolated from M. ferruginea were evaluated in human ovarian cancer cells. We found that isoflavone ferrugone and 6,7-dimethoxy-3’,4’-methylenedioxy-8-(3,3-dimethylallyl)isoflavone (DMI) had potent cytotoxic effects on human ovarian cancer cell A2780 and SKOV3. Ferrugone and DMI treatment increased the sub-G1 cell population in a dose-dependent manner in A2780 cells. The cytotoxic activity of ferrugone and DMI was associated with the induction of apoptosis, as shown by an increase in annexin V-positive cells. Z-VAD-fmk, a broad-spectrum caspase inhibitor, and z-DEVD-fmk, a caspase-3 inhibitor, significantly reversed both the ferrugone and DMI-induced apoptosis, suggesting that cell death stimulated by the isoflavones is mediated by caspase-3-dependent apoptosis. Additionally, ferrugone-induced apoptosis was found to be caspase-8-dependent, while DMI-induced apoptosis was caspase-9-dependent. Notably, DMI, but not ferrugone, increased the intracellular levels of reactive oxygen species (ROS), and antioxidant N-acetyl-L-cysteine (NAC) attenuated the pro-apoptotic activity of DMI. These data suggest that DMI induced apoptotic cell death through the intrinsic pathway via ROS production, while ferrugone stimulated the extrinsic pathway in human ovarian cancer cells.

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“…For the in vivo experiments, estradiol benzoate (E2B) and faslodex were administered subcutaneously at the doses of 2 μg/kg and 300 μg/kg, respectively as described by Zingue et al [ 19 ]. The well-known phytoestrogen genistein was administered at a dose of 10 mg/kg [ 20 ].…”

Section: Methodsmentioning

confidence: 99%

Estrogen-like and tissue-selective effects of 7-methoxycoumarin from Ficus umbellata (Moraceae): an in vitro and in vivo study

Zingue

Michel

Nde

et al. 2017

BMC Complement Altern Med

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Background Ficus umbellata is a medicinal plant previously shown to endow estrogenic properties. Its major component was isolated and characterized as 7-methoxycoumarin (MC). Noteworthy, coumarins and the respective active metabolite 7-hydroxycoumarin analogs have shown aromatase inhibitory activity, which is of particular interest in the treatment of estrogen-dependent cancers. The present work aimed at evaluating the estrogenic/antiestrogenic effects of MC in vitro and in vivo.MethodsTo do so, in vitro assays using E-screen and reporter gene were done. In vivo, a 3-day uterotrophic assay followed by a postmenopausal-like rat model to characterize MC as well as F. umbellata aqueous extract in ovariectomized Wistar rats was performed. The investigations focused on histological (vaginal and uterine epithelial height) and morphological (uterine wet weight, vagina stratification and cornification) endpoints, bone mass, biochemical parameters and lipid profile.ResultsMC induced a significant (p < 0.05) MCF-7 cell proliferation at a concentration of 0.1 μM, but did not inhibit the effect induced by estradiol in both E-screen and reporter gene assays. In vivo, MC treatment did not show an uterotrophic effect in both rat models used. However, MC (1 mg/kg) induced a significant increase (p < 0.01) of vaginal epithelial height. No significant change was observed with MC in abdominal fat weight, serum lipid levels and bone weight.ConclusionThese results suggest that MC has a weak estrogenic activity in vitro and in vivo that accounts only in part to the estrogenicity of the whole plant extract. MC could be beneficial with regard to vagina dryness as it showed a tissue specific effect without exposing the uterus to a potential tumorigenic growth.Electronic supplementary materialThe online version of this article (doi:10.1186/s12906-017-1895-9) contains supplementary material, which is available to authorized users.

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Elucidation of Underlying Mechanisms by WhichMillettia macrophyllaBenth Induces Its Estrogenic Activity

Cited by 5 publications

References 29 publications

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

Isoflavones Isolated from the Seeds of Millettia ferruginea Induced Apoptotic Cell Death in Human Ovarian Cancer Cells

Estrogen-like and tissue-selective effects of 7-methoxycoumarin from Ficus umbellata (Moraceae): an in vitro and in vivo study

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