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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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Acute-on-chronic liver failure (ACLF) is a condition characterized by acute decompensation of cirrhosis, associated with organ failure(s), and high short-term mortality. The microRNAs or miRNAs are small non-coding RNA molecules, stable in circulating samples such as biological fluids, and the difference in expression levels may indicate the presence, absence and/or stage of the disease. We analyzed here the miRNA profiling to identify potential diagnostic or prognostic biomarkers for ACLF. The major miRNAs discovered were validated in a cohort of patients with acute decompensation of cirrhosis grouped in no ACLF or ACLF according to EASL-CLIF definition. Relationship between serum miRNAs and variables associated with liver-damage and survival outcomes were verified to identify possible prognostic markers. Our results showed twenty altered miRNAs between no ACLF and ACLF patients, and twentyseven in patients who died in 30 days compared with who survived. In validation phase, miR-223-3p and miR-25-3p were significantly altered in ACLF patients and in those who died in 30 days. miR-223-3p and miR-25-3p expression were associated with the lowest survival in 30 days. The decrease in miR-223-3p and miR-25-3p expression was associated with the presence of ACLF and poor prognosis. Of these, miR-25-3p was independently related to ACLF and 30-day mortality. The natural history of cirrhosis is usually characterized by a long-standing compensated phase followed by a transition to the decompensated disease, identified by the occurrence of specific complications of cirrhosis, such as ascites, variceal bleeding, and hepatic encephalopathy 1. Patients with both compensated or decompensated cirrhosis are at risk of progression to acute-on-chronic liver failure (ACLF), a condition characterized by an acute deterioration of the liver function and characterized by progression to extrahepatic organ failure and high short-term mortality 2,3. Although a precise definition is still lacking, the European Association for the Study of the Liver-Chronic Liver Failure (EASL-CLIF) Consortium definition is one of the most validated criteria for ACLF in patients with cirrhosis and it is based on a modified version of SOFA score called CLIF-SOFA 2,4. According to a recently published study 5 , mortality rates in ACLF patients are 25.5% and 40% in 28 and 90 days of admission, respectively. Therefore, searching for new biomarkers associated with the presence of ACLF and prognosis of patients with acute decompensation of cirrhosis may improve clinical decision and help to implement risk-adapted treatment strategies. In recent years, miRNAs have been studied as promising biomarkers for the diagnosis and prognostic in many clinical scenarios 6-8 , including liver diseases 9. The miRNAs are a group of small non-coding RNAs, with approximately 22 nucleotides, which post-transcriptionally regulate gene expression

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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.