Chantal Beatrice Magne Nde

Preventive Effects of an Extract of Erythrina Lysistemon (Fabaceae) on Some Menopausal Problems: Studies on the Rat

Objective - Our purpose was to determine the advantage of early treatment (before ovariectomy) on a preventive basis of an ethyl acetate extract of Erythrina lysistemon (EL) on menopausal signs, an extract which has previously shown estrogenic activity by acting through the oestrogen receptors.Methods - Female Wistar rats aged 1-1.5 month were randomised in groups and treated respectively from 28 days before ovariectomy to 84 days after. The fasting lipids levels, glucose tolerance, bone and uterine weight, uterine and vaginal epithelial height were determined at days 0, 28, 56 and 84; whereas body weight was determined every forth night.Results - Oral administration of 200mg/kg/d of EL significantly increased HDL-cholesterol and LDL-cholesterol levels on days 0 and 28 and decreased them at days 56 (70%) and 84 (48.27%) compared to untreated ovariectomized rats. It also significantly increased bone weight. Further, EL at day-56 controlled glucose intolerance; but it failed to do so at day-84 and significantly increased blood glucose level. At day 0, EL significantly decreased uterine weight of animals as well as E1. In contrast 28 days after ovariectomy, EL significantly increased uterine weight (36.43%), uterine (19.71%) and vaginal (31.76%) epithelial height with a more advance vaginal cornification compared to controls.Conclusion - These results suggest that oral administration of 200mg/kg/d of EL 28 days before ovariectomy prevented bone loss. EL had a transient effect on glucose intolerance. However EL significantly increased HDL-cholesterol and decreased TG levels.

Crateva adansonii DC, an African ethnomedicinal plant, exerts cytotoxicity in vitro and prevents experimental mammary tumorigenesis in vivo

ETHNOPHARMACOLOGICAL RELEVANCE Crateva adansonii DC is a plant traditionally used in Cameroon to treat constipation, asthma, snakebites, postmenopausal complaints and cancers. AIM The anticancer potential of the dichloromethane/methanol extract of C. adansonii stem barks was investigated using human breast cancer cell and 7,12 dimethylbenz(a)anththracene (DMBA)-induced mammary tumorigenesis model in rats. MATERIAL AND METHODS The cytotoxicity of C. adansonii extract was assessed in vitro towards breast carcinoma (MCF-7 and MDA-MB-231) and non-tumoral cell lines (NIH/3T3 and HUVEC) by Alamar Blue assay. Furthermore, in vivo studies were performed on female Wistar rats treated either with C. adansonii extract at a dose of 75 or 300mg/kg body weight or with tamoxifen (3.3mg/kg body weight), starting 1 week prior DMBA treatment and lasted 12 weeks. The investigation focused on tumour burden, tumour DNA fingerprint, morphological, histological, hematological, and biochemical parameters. RESULTS CC50 values for the in vitro assays were 289µg/mL against MCF-7 cells and >500µg/mL in others cells, leading to a selectivity index ≥1.73. C. adansonii extract significantly (p<0.001) revealed in vivo the reduction of the cumulative tumour yield (87.23%), total tumour burden (88.64%), average tumour weight (71.11%) and tumour volume (78.07%) at the dose of 75mg/kg as compared to DMBA control group. A weak effect was also observed at 300mg/kg. This extract showed a moderate hyperplasia at the dose of 75mg/kg while at 300mg/kg no significant change was noted as compared to DMBA group. It protected rats from the DNA alteration induced by DMBA and increased antioxydant enzymes activities in mammary gland tissue homogenates. In addition, Ultra-High Performance Liquid Chromatography/ESI-QTOF-Mass Spectrometry analysis of C. adansonii extract detected structure-related of many well-known anticancer agents such as flavane gallate, flavonol, phenylpropanoïds, sesquiterpene derivatives, gallotannins and lignans. The LD50 of C. adansonii was estimated to be greater than 5000mg/kg. CONCLUSIONS These aforementioned results suggest that the C. adansonii extract may possess antitumor constituents, which could combat breast cancer and prevent chemically-induced breast cancer in rats.

Elucidation of Underlying Mechanisms by Which Millettia macrophylla Benth Induces Its Estrogenic Activity

Millettia macrophylla is used traditionally to treat menopause related symptoms. This plant was shown to exhibit estrogenic effects in vitro on human embryonic kidney cells and in vivo on ovariectomized rats. The present study aimed at elucidating underlying mechanisms by which M. macrophylla induced its estrogenic effects. To accomplish our goal, kidney Hek293T cells transiently transfected with estrogen alpha or beta receptor expression plasmids were cotreated with a pure antiestrogen ICI 182,780 and the dichloromethane or methanol soluble fractions of M. macrophylla. To follow up, we cotreated ovariectomized rats with both extracts and ICI 182,780 for 3 days in the classical uterotrophic assay. Animals were then sacrificed and the uterine wet weight, total protein levels in uteri, uterine, and vaginal epithelial heights, and mammary gland were assessed. In vitro, the results suggested that the induction of the estrogenic activity by M. macrophylla is due to the binding of its secondary metabolites to ERα and ERβ. In vivo, the cotreatment of extracts and ICI 182,780 significantly abrogated the biological responses induced by the extracts alone. Taken together, these results indicate that the active principles of M. macrophylla induce their beneficial effects on menopausal symptoms by activating the ERs.

The methanol-soluble fraction of Millettia macrophylla (Fabaceae) stem bark endowed with estrogenic properties has adverse effects on the male reproductive system of Wistar rats

Abstract Background: The use of traditional medicinal plants to treat various diseases is common in Sub-Saharan African countries, including Cameroon. Millettia macrophylla, one of such plants, was previously found to exhibit estrogenic properties in female Wistar rats. However, its effects on the male reproductive system are unknown. Based on literature evidence that phytoestrogens impair male sexual behavior, we aimed at assessing the effect of the extracts of M. macrophylla stem bark on the male reproductive system of Wistar rats. Materials and methods: We evaluated the effects of the dichloromethane (DCM) and methanol (MeOH) soluble fractions of M. macrophylla stem bark on male rat sexual behavior, as well as androgen-dependent parameters for 60 days. Results: Data showed a significant decrease (p<0.05) in the wiring-touch frequency, mount frequency, intromission frequency, ejaculatory frequency, penile-licking frequency, and computed indices of sexual behavior, throughout the experimental period, as well as a significant increase (p<0.001) in mount, intromission, and ejaculatory latencies as well as post-ejaculatory interval. Moreover, we observed a significant decrease (p<0.05) in the androgen-dependent sexual parameters evaluated. The DCM extract did not induce significant effects on the assessed parameters. Conclusions: These results suggest that long-term exposure to the estrogenic MeOH fraction of M. macrophylla stem bark negatively alters sexual behavior and spermatogenesis.

Timeless Is a Novel Estrogen Receptor Co-activator Involved in Multiple Signaling Pathways in MCF-7 Cells

Activation of estrogen receptor α (ERα) stimulates cell division and tumor growth by modulating the expression of ERα target genes. This activation involves the recruitment of specific proteins with activities that are still not fully understood. Timeless, the human homolog of the Drosophila gene involved in circadian rhythm, was previously shown to be a strong predictor of tamoxifen relapse, and is involved in genomic stability and cell cycle control. In this study, we investigated the interplay between Timeless and ERα, and showed that human Timeless is an ERα coactivator. Timeless binds to ERα and enhances its transcriptional activity. Overexpressing Timeless increases PARP1 expression and enhances ERα-induced gene regulation through the proximal LXXLL motif on Timeless protein and ERα PARylation. Finally, Timeless is recruited with ERα on the GREB1 and cMyc promoters. These data, the first to link Timeless to steroid hormone function, provide a mechanistic basis for its clinical association with tamoxifen resistance. Thus, our results identify Timeless as another key regulator of ERα in controlling ERα transactivation.

The Efficacy of Some Comestible Natural Products in Treatment of Cancer

Despite the fact that cancer is primarily a preventable disease, recent statistics indicate cancer is the number one killer worldwide. Conventionally, cancer therapy includes surgery, radiation and drugs, separately or in combination. This modality of cancer treatment is still not successful. Therefore, the identification of new cytotoxic drugs with low or none side effects is of great interest worldwide. Since traditional medicines have been used for maintaining health, as well as in the prevention, therapy and remission of cancer, natural products can serve as chemopreventive and chemotherapeutic agent. Here, we describe the efficacy of 3 comestible natural products such as garlic, green tea and cruciferous vegetables in cancer therapy.