Sylvin Benjamin Ateba

Eriosema laurentii De Wild (Leguminosae) methanol extract has estrogenic properties and prevents menopausal symptoms in ovariectomized Wistar rats

ETHNOPHARMACOLOGICAL RELEVANCE Eriosema laurentii De Wild (Leguminosae) is a medicinal plant used in West and Central Africa for different diseases. In Cameroon, this plant is used as a treatment for infertility, and various gynecological and menopausal complaints. However, despite this use as a natural remedy, the biological activity of Eriosema laurentii has not been studied until now. AIM OF STUDY In order to determine the potential use of this plant in gynecological conditions/disorders, we evaluated the estrogenic properties of a methanol extract of its aerial parts and its ability to prevent different menopausal health problems induced by bilateral oophorectomy. MATERIAL AND METHODS Two approaches were used. In vitro, recombinant yeast systems were applied, featuring either the respective human receptors (ERα, AR, and PR) or into chromosome III integrated human aryl hydrocarbon receptor (AhR) and the respective reporter plasmid. In vivo, the investigation was carried out using the 3 days uterotrophic assay and 9 weeks oral treatment in ovariectomized rats. RESULTS The results showed that the methanol extract of the aerial parts of Eriosema laurentii transactivated the estrogen receptor-α and displayed AhR agonistic activity but was neither androgenic nor progesteronic. In rats, the extract did not induce endometrium proliferation either in the 3-day or the 9-week treatment regimens, but induced vaginal stratification and cornification, prevented loss of femur bone mass, increased high density lipoprotein cholesterol (HDL-C), and reduced total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), TC/HDL-C ratio, LDL-C/HDL-C ratio and the atherogenic index of plasma (AIP). CONCLUSION These results suggest that the methanol extract of the aerial parts of Eriosema laurentii does not seem to have an undesirable influence on the endometrium but might prevent vaginal dryness and bone mass loss and improve the lipid profile.

Safety profile and gender specific differences of a methanol extract of Eriosema laurentii (Leguminosae) in acute and subchronic (28 days) oral toxicity studies in Wistar rats

Despite widespread use of Eriosema laurentii De Wild (Leguminosae) in West and Central Africa as herbal medicine and food additive the toxicity of this plant is unknown. Therefore, we performed the safety evaluation of a methanol extract (AEL). In acute toxicity, single oral administration of 2000mg/kg AEL caused neither toxicological symptoms nor mortality and the LD50 was estimated >5000mg/kg. In the subchronic oral toxicity, AEL induced no phenotypical signs of toxicity during and after treatment. Only a delayed decrease of relative spleen weight in males at the highest dose of 400mg/kg occurred. High density lipoprotein (HDL) increased significantly in females at 200 and 400mg/kg. Non-persistent increases in alanine aminotransferase activity within normal ranges were noted at 200mg/kg in males and at all doses in females. In males, AEL induced a decrease of white blood cell count at 400mg/kg, whereas lymphocytes increased at 200 and 400mg/kg and granulocytes at 400mg/kg. In females, no differences in haematological parameters occurred. Neither differences in bilirubin, creatinine and total protein levels were observed nor histological alterations in organs. The results indicate a broad safety margin for AEL.

Estrogenic properties of spices of the traditional Cameroonian dish “Nkui” in ovariectomized Wistar rats

Abstract Background: Besides the basic role to flavor and color foods, several health benefits have been attributed to spices. The traditional Cameroonian food “Nkui” is prepared using several spices (Afrostyrax lepidophyllus Mildbr., Capsicum frutescens Linn., Fagara leprieurii Guill. et Perr., Fagara tessmannii Engl., Mondia whitei Hook. F. Skell., Pentadiplandra brazzeana Baill., Solanum gilo Raddi., Tetrapleura tetraptera Taub. and Xylopia parviflora A. Rich. Benthane) that are believed to have a positive impact on the female reproductive physiology. Aiming to determine the potential effect of this food on the female reproductive tract, we evaluated the estrogenic properties of aqueous and ethanol extracts of Nkui using a 3-day uterotrophic assay in ovariectomized (OVX) rats. Methods: OVX female Wistar rats were randomly separated in several groups of five animals each and submitted to a 3-day uterotrophic assay (per os). At the end of treatment, animals were sacrificed and uterus, vagina and mammary gland collected and fixed in 10 % formalin for histological analysis. Results: These extracts increased the uterine wet weight, the uterine and vaginal epithelial heights, and the lumen and diameter of alveoli in the mammary glands. They also altered the estradiol-induced increase of uterine wet weight. The dichloromethane and methanol fractions of the ethanol extract exhibited estrogenic properties as well by increasing uterine and vaginal endpoints. Conclusions: These results suggest that the spices of “Nkui” contain estrogenic phytoconstituents and this traditional food may be considered as functional.

Potential Antiosteoporotic Natural Product Lead Compounds That Inhibit 17β-Hydroxysteroid Dehydrogenase Type 2

17β-Hydroxysteroid dehydrogenase type 2 (17β-HSD2) converts the active steroid hormones estradiol, testosterone, and 5α-dihydrotestosterone into their weakly active forms estrone, Δ4-androstene-3,17-dione, and 5α-androstane-3,17-dione, respectively, thereby regulating cell- and tissue-specific steroid action. As reduced levels of active steroids are associated with compromised bone health and onset of osteoporosis, 17β-HSD2 is considered a target for antiosteoporotic treatment. In this study, a pharmacophore model based on 17β-HSD2 inhibitors was applied to a virtual screening of various databases containing natural products in order to discover new lead structures from nature. In total, 36 hit molecules were selected for biological evaluation. Of these compounds, 12 inhibited 17β-HSD2 with nanomolar to low micromolar IC50 values. The most potent compounds, nordihydroguaiaretic acid (1), IC50 0.38 ± 0.04 μM, (−)-dihydroguaiaretic acid (4), IC50 0.94 ± 0.02 μM, isoliquiritigenin (6), IC50 0.36 ± 0.08 μM, and ethyl vanillate (12), IC50 1.28 ± 0.26 μM, showed 8-fold or higher selectivity over 17β-HSD1. As some of the identified compounds belong to the same structural class, structure–activity relationships were derived for these molecules. Thus, this study describes new 17β-HSD2 inhibitors from nature and provides insights into the binding pocket of 17β-HSD2, offering a promising starting point for further research in this area.

Myrianthus arboreus P. Beauv (Cecropiaceae) Extracts Accelerates Sexual Maturation, and Increases Fertility Index and Gestational Rate in Female Wistar Rats

Background: Despite the wide use of leaves of Myrianthus arboreus (Cecropiaceae) in several African countries including Cameroon as food and against amenorrhea and female infertility, it has never been tested for this purpose. Methods: Using immature female Wistar rats, the impact of M. arboreus on the sexual maturation parameters (vaginal opening, ovarian relative weight and follicle maturation, gonadotropins and ovarian hormones serum levels) and fertility index has been evaluated through a 30-day oral administration of aqueous and methanol extracts of leaves at the doses of 20, 110 and 200 g/kg/day. Results: Aqueous extract increased the ovarian relative weight (p < 0.001), progesterone (p < 0.001) and gonadotropins (p < 0.001) serum levels, and induced the maturation of ovarian follicles. The methanol extract additionally induced an early vaginal opening (p < 0.001), uterine growth (p < 0.01) and increased estradiol (p < 0.001) serum levels. The fertility index generally increased following treatments, while the gestation rate remained almost unaffected except at the highest tested dose of M. arboreus extracts where lowest values were observed. Conclusion: Globally, M. arboreus induced an early puberty onset and an increased fertility rate validating at least in part its traditional use for female infertility.

Lannea acida A. Rich. (Anacardiaceae) Ethanol Extract Exhibits Estrogenic Effects and Prevents Bone Loss in an Ovariectomized Rat Model of Osteoporosis

Phytoestrogens have been shown to prevent postmenopausal osteoporosis. Lannea acida is a medicinal plant traditionally used in Cameroon to treat infertility, gynaecological complaints, and rheumatism. These uses prompted us to evaluate estrogenic activity of Lannea acida bark ethanolic extract and its antiosteoporotic potential in ovariectomized Wistar rats. In vitro, the E-screen assay was used to assess the ability of L. acida extract to induce MCF-7 cells proliferation. In vivo, a 3-day uterotrophic assay and a 12-week oral treatment in ovariectomized adult rats were carried out to evaluate the ability of L. acida extract to prevent bone mass loss. L. acida extract induced MCF-7 cell proliferation. In vivo, it significantly increased the uterine wet weight, uterine and vaginal epithelial heights, and mammary glands differentiation. At 200 mg/kg, a long-term treatment with the extract prevented body weight gain (p < 0.05) and loss of bone mass and/or density (p < 0.05) induced by ovariectomy. Also, a significant (p < 0.001) decrease of alkaline phosphatase activity was observed with 50 mg/kg. L. acida extract improved bone microarchitecture and could restore normal bone mineralization by increasing the inorganic phosphorus and calcium level in bone. These findings provide evidence that Lannea acida is a potential alternative for the prevention of postmenopausal osteoporosis.

The Root Aqueous Extract of Entada africana Guill. et Perr. (Mimosaceae) Inhibits Implant Growth, Alleviates Dysmenorrhea, and Restores Ovarian Dynamic in a Rat Model of Endometriosis

Entada africana (Mimosaceae) was reported to have analgesic and antioxidant properties. The present study is aimed at investigating the effects of the root aqueous extract of Entada africana (EA) on an experimental model of endometriosis. The study was performed in rats orally treated with EA at doses of 127.5, 255, and 510 mg/kg. Microgynon® 30 served as the reference substance. Estradiol valerate and oxytocin were used to induce dysmenorrhea. Endometrial implant levels of catalase and malondialdehyde (MDA) allowed estimating tissue oxidative status. Ovarian dynamic and rat sexual behavior were assessed through histological analysis of ovaries, uterus, and vagina. EA decreased dysmenorrhea at tested doses following a 7-day treatment (p < 0.001). Endometrial implant volume decreased following the three treatment periods (p < 0.05). Catalase activity (p < 0.001) and MDA level (p < 0.01) increased only following a 3-day treatment. EA also increased antral follicles, reduced luteinized unruptured follicle number (p < 0.001), and induced animals to be in the estrus phase. In conclusion, EA prevented the progress of endometriosis, reduced dysmenorrhea, promoted ovarian follicle growth, prevented anovulation, and stimulated the special period of rat sexual desire. These results suggest that Entada africana could be a promising alternative option for the treatment of endometriosis.