title: 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.
  
  
  METHODS
  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.
  
  
  RESULTS
  Seven of the 13 secondary metabolites turned to be estrogenic. Only two exhibited cytotoxic effects on MCF-7 and MDA-MB-231 with CC50values 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 10-2μg/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.
  
  
  CONCLUSIONS
  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.
authors: Laboratory of Physiology and Natural Products Research, Department of Live and Earth Sciences, Higher Teachers' Training College, University of Maroua, P.O. Box 55, Maroua, Cameroon. stephanezingue@gmail.com.|Department of Animal Biology and Physiology, Faculty of Sciences, University of Yaoundé I, P.O. Box 812, Yaoundé, Cameroon. stephanezingue@gmail.com.|Division of Pharmacognosy and Natural Products Chemistry, School of Pharmacy, University of Athens, Panepistimioupoli Zografou, 15771, Athens, Greece. stephanezingue@gmail.com.|Department of Pharmaceutical Sciences, Health Sciences Centre, Federal University of Santa Catarina, CEP 88040-900, Florianópolis, Santa Catarina, Brazil. stephanezingue@gmail.com.
authors: Stéphane
authors: S
authors: Zingue
authors: Department of Animal Biology and Physiology, Faculty of Sciences, University of Yaoundé I, P.O. Box 812, Yaoundé, Cameroon.|Division of Pharmacognosy and Natural Products Chemistry, School of Pharmacy, University of Athens, Panepistimioupoli Zografou, 15771, Athens, Greece.
authors: Job
authors: J
authors: Tchoumtchoua
authors: Department of Animal Biology and Physiology, Faculty of Sciences, University of Yaoundé I, P.O. Box 812, Yaoundé, Cameroon.
authors: Dieudonnée Mireille
authors: DM
authors: Ntsa
authors: Department of Pharmaceutical Sciences, Health Sciences Centre, Federal University of Santa Catarina, CEP 88040-900, Florianópolis, Santa Catarina, Brazil.
authors: Louis Pergaud
authors: LP
authors: Sandjo
authors: Department of Pharmaceutical Sciences, Health Sciences Centre, Federal University of Santa Catarina, CEP 88040-900, Florianópolis, Santa Catarina, Brazil.
authors: Julia
authors: J
authors: Cisilotto
authors: Hudson Institute of Medical Research, Clayton, VIC, 3168, Australia.
authors: Chantal Beatrice Magne
authors: CBM
authors: Nde
authors: Department of Pharmaceutical Sciences, Health Sciences Centre, Federal University of Santa Catarina, CEP 88040-900, Florianópolis, Santa Catarina, Brazil.
authors: Evelyn
authors: E
authors: Winter
authors: Department of Animal Biology and Physiology, Faculty of Sciences, University of Yaoundé I, P.O. Box 812, Yaoundé, Cameroon.
authors: Charline Florence
authors: CF
authors: Awounfack
authors: Department of Applied Chemistry, Faculty of Sciences, University of Johannesburg, Doornfontein, 2028, South Africa.
authors: Derek Tantoh
authors: DT
authors: Ndinteh
authors: Hudson Institute of Medical Research, Clayton, VIC, 3168, Australia.
authors: Colin
authors: C
authors: Clyne
authors: Department of Animal Biology and Physiology, Faculty of Sciences, University of Yaoundé I, P.O. Box 812, Yaoundé, Cameroon.|Department of Applied Chemistry, Faculty of Sciences, University of Johannesburg, Doornfontein, 2028, South Africa.
authors: Dieudonné
authors: D
authors: Njamen
authors: Division of Pharmacognosy and Natural Products Chemistry, School of Pharmacy, University of Athens, Panepistimioupoli Zografou, 15771, Athens, Greece.
authors: Maria
authors: M
authors: Halabalaki
authors: Department of Pharmaceutical Sciences, Health Sciences Centre, Federal University of Santa Catarina, CEP 88040-900, Florianópolis, Santa Catarina, Brazil. tania.pasa@ufsc.br.
authors: Tânia Beatriz
authors: TB
authors: Creczynski-Pasa
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004967:Estrogens / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity*; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D033641:Millettia / Q000737:chemistry*; D010052:Ovariectomy; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity*; D051381:Rats; D014599:Uterus / Q000737:chemistry / Q000187:drug effects; D014621:Vagina / Q000166:cytology / Q000187:drug effects
chemical_list: D004967:Estrogens; D010936:Plant Extracts
keywords: Cytotoxicity; E-screen assay; Estrogen-dependent cancer; Millettia macrophylla; Phytoestrogens; Uterotrophic assay