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

The present work deals with the assessment of the in vitro and in vivo estrogenic effects of the triterpenoids (lupenone, lupeol, and stigmastenone) isolated from Millettia macrophylla extract. The in vitro estrogenicity was performed by a reporter gene assay and estrogen receptor-α (ERα) target gene expression, whereas the in vivo estrogenicity was evaluated by a 3-day uterotrophic assay in ovariectomized rats. As results, lupenone and lupeol did not transactivate ERα as well as ERß of human embryonic kidney 293T (HEK293T) cells. However, lupeol seems to be antagonistic to estrogen (E2) only in HEK293T-ERα (10-9 and 10-8  µM). Furthermore, lupeol slightly upregulated GREB1 gene expression at the concentration of 1 µM, suggesting a weak activation of endogenous ERα. In vivo, only lupeol at a dose of 1 mg/kg significantly increased the uterine wet weight (p < 0.05), uterine (p < 0.05), and vaginal (p < 0.01) epithelial heights. The concomitant administration of lupeol (1 mg/kg) with a pure antiestrogen fulvestrant abrogated its effects only in the vagina, whereas in combination with E2, lupeol exhibited a significant antiestrogen-like effect in uterine wet weight and synergistic effects on endometrium. Lupeol has estrogenic effects that is partly through ERs transcriptional activity and does involve alternative mechanisms that are still to be uncovered.

Abyssinone V-4' Methyl Ether Isolated from Erythrina droogmansiana (Leguminosae) Inhibits Cell Growth and Mammary Glands Hyperplasia Induced in Swiss Mice by the 7,12-Dimethylbenz(a)anthracene.

There is a long standing interest in the identification of medicinal plants and derived natural products for developing cancer therapeutics. The present study was designed to evaluate the in vitro and in vivo antiproliferative effects of Abyssinone V-4' methyl ether (AVME) on breast tissue of mice. The cytotoxicity of AVME was evaluated using MTT assay in four cancer cell lines (DU145, PC3, HepG2, and MCF-7). Further, a protective effect of AVME was evaluated on 7,12-dimethylbenz(a)anthracene- (DMBA-) induced breast tumor in Swiss mice. Incidence, burden, volume, and histological analysis of mammary tumors were measured. As a result, AVME inhibits DU145, PC3, HepG2, and MCF-7 cells growth. In vivo, no tumor was detected in mice from the normal group as compared to those of DMBA group. Moreover, AVME inhibits the DMBA-induced mammary glands hyperplasia in mice at the dose of 10 mg/kg, evidenced by a decrease of tumor incidence, tumor weight, and volume as well as a protective effect against the lobular alveolar hyperplasia. Taken all together, these results suggest that Abyssinone V-4' methyl ether is endowed with antitumor properties and could be a source of traditional medicine which deserves to be more elucidated and explored in the foreseeable future.

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

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 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 ERß 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. CONCLUSION: 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.