Oleocanthal Modulates Estradiol-Induced Gene Expression Involving Estrogen Receptor α

Oleocanthal is a bioactive compound from olive oil. It has attracted considerable attention as it is anti-inflammatory, antiproliferative, and has been shown to possess neuroprotective properties in vitro and in vivo. Delineated from its polyphenolic structure, the aim of this study was to characterize oleocanthal towards estrogenic properties. This might contribute to partly explain the beneficial effects described for the Mediterranean diet. Estrogenic properties of oleocanthal were assessed by different methods: a) stimulation of reporter gene activity in MVLN or RNDA cells either expressing estrogen receptor α or β, b) stimulation of luciferase reporter gene activity in U2OS osteosarcoma cells expressing estrogen receptor α or β, and c) elucidation of the impact on estradiol-induced gene expression in U2OS cells transduced with both estrogen receptors. Depending on the cell line origin, oleocanthal inhibited luciferase activity (MVLN, U2OS-estrogen receptor β) or weakly induced reporter gene activity at 10μM in U2OS-estrogen receptor α cells. However, oleocanthal inhibited stimulation of luciferase activity by estradiol from both estrogen receptors. Oleocanthal, if given alone, did not stimulate gene expression in U2OS cells, but it significantly modulated the response of estradiol. Oleocanthal enhanced the effect of estradiol on the regulation of those genes, which are believed to be regulated through heterodimeric estrogen receptors. As the estrogenic response pattern of oleocanthal is rather unique, we compared the results obtained with oleacein. Oleocanthal binds to both estrogen receptors inducing estradiol-agonistic or antiagonistic effects depending on the cell line. Regarding regulation of gene expression in U2OS-estrogen receptor α/β cells, oleocanthal and oleacein enhanced estradiol-mediated regulation of heterodimer-regulated genes. © Georg Thieme Verlag KG Stuttgart · New York

Estrogenic and anxiolytic effects of the decoction of stem bark of Khaya anthotheca (Welw.) C.DC (Meliaceae) in ovariectomised Wistar rats

Khaya anthotheca (Welw.) C.DC (Meliaceae) is a plant used in Cameroon to alleviate vaginal dryness in postmenopausal women and is also known to have anxiolytic properties.This work was designed to evaluate estrogen-like effects of this plant on primary estrogens targets of ovariectomized adult rats, as well as to evaluate its anxiolytic activities in the elevated plus-maze (EPM) test. In the 3-day uterotrophic assay, the extract increased (p < 0.01) the size of the vaginal epithelia and stimulated the acini differentiation of the mammary gland. In the EPM test, the extract increased the percentage of number of entries (p <0.05; p <0.01) and the percentage of time spent (p < 0.05) into open arms.Italso induced a decrease in percentage of number of entries (p < 0.05; p < 0.01) and the percentage of time spent (p < 0.05) into closed arms. The extract also induced an increase of total arms entries (p < 0.05; p < 0.01) and rearing (p < 0.05). Moreover, there was a decrease of defecation and grooming (p < 0.05; p < 0.01). These results suggest that K. anthotheca is endowed with estrogenic and anxiolytic properties, likely due to the presence of some estrogen-like compounds

Isoflavonoids from Erythrina poeppigiana: Evaluation of their binding affinity for the estrogen receptor

Five new isoflavones, named 5,4′-dihydroxy-7-methoxy-3′-(3- methylbuten-2-yl)isoflavone (1), 5,2′,4′-trihydroxy-7-methoxy- 5′-(3-methylbuten-2-yl)isoflavone (2), 5,4′-dihydroxy-7-methoxy- 3′-(3-methyl-2-hydroxybuten-3-yl)isoflavone (3), 3′-formyl-5, 4′-dihydroxy-7-methoxyisoflavone (4), and 5-hydroxy-3″-hydroxy- 2″,2″-dimethyldihydropyrano[5″,6″: 3′,4′] isoflavone (5), as well as six known compounds, wighteone (6), 3′-isoprenylgenistein (7), isolupabigenin (8), alpinumisoflavone (9), erypoegin D (10), and crystacarpin (11), were isolated from Erythrina poeppigiana. The structures of the isolated compounds were elucidated on the basis of chemical and spectroscopic analysis. The affinity of these compounds for the estrogen receptors ERα and ERβ was evaluated using a receptor binding assay. While isoprenyl and dimethylpyrano substituents in ring A reduced the affinity of binding to ERβ ca. 100-fold compared to genistein, the isoprenyl substituent in ring B was better accommodated, allowing 7 to bind with ca. 10-fold lower affinity than genistein. © 2009 American Chemical Society and American Society of Pharmacognosy

Effect of spices formulations on the physicochemical and sensory properties of Nnam gon, a Cameroonian dish prepared with cucurbitaceae seeds

Nnam gon, a cake made by steam cooking a mixture of Cucurbitaceae seeds paste and others ingredients specially spices, is a highly prized dish in Central African region. A preliminary investigation conducted as part of this study highlighted that formulations used in the processing of Nnam gon vary according to the spices used. This study was carried out to determine the best formulation for the preparation of this dish. For this purpose, Nnam gon samples were produced from four formulations which differ according to the number of spices used: F0 (no spices); F1 (0.91 g of Allium cepa paste); F2 (0.88 g of A. cepa paste, 0.35 g of Allium sativum paste, 0.41 g of fresh Officinale zingiber paste, 0.41 g of fresh Petroselinum crispum paste, 0.33 g of Monodora myristica, 0.48 g of fresh Celery graveolens paste, 1.19 g of fresh Allium porrum paste, 0.13 g of Allium lepidophyllus powder, and 0.13 g of Piper nigrum), and F3 (0.90 g of A. cepa paste, 0.35 g of A. sativum paste, and 0.42 g of fresh O. zingiber paste). The samples were evaluated for their physicochemical characteristics and sensory profile (Quantitative Descriptive Analysis). The results revealed that proteins (16.56–17.38%), carbohydrates (4.71–5.10%), lipids (23.14–24.25%), ash (4.03–5.92%), and fibers (2.17–2.68%) increased significantly (p < .05) with spices adding. The increase in polyphenols (310.55–592.80 mg/100 g FM) and phytates (2.23–12.49 mg/100 g FM) contents was positively correlated with antioxidant properties of Nnam gon which also increased with spices adding. Significant differences were observed between the samples for all attributes generated (appearance, odor, taste, flavor, texture, and oral texture). Spices adding induced a decrease in hardness, cohesivity, elasticity, and granulous of cake but enhanced oily. Nnam gon produced with spicy formulation (F2 and F3) had higher mean score for general acceptance which was highly correlated (p < .05) with spice odor (r = .99), spice taste (r = .92), and color (r = .84). From this study, it is suggested that spicy Cucurbitaceae paste could improve nutritional value, antioxidant properties, and general acceptance of Nnam gon

Effects of Ficus umbellata (Moraceae) Aqueous Extract and 7-Methoxycoumarin on Scopolamine-Induced Spatial Memory Impairment in Ovariectomized Wistar Rats

The present work was undertaken to evaluate the ability of F. umbellata aqueous extract and its major component 7-methoxycoumarin (MC) to improve scopolamine-induced spatial memory impairment in ovariectomized Wistar rats. For this to be done, 10 sham-operated and 30 postmenopausal-like rats were randomly distributed in eight groups (n=5) and treated with distilled water (2 mL/250 g), estradiol valerate (1 mg/kg BW), piracetam (1.5 mg/kg BW), F. umbellata aqueous extract (50 and 200 mg/kg BW), or MC (1 mg/kg BW) for 21 consecutive days. Before and after the memory impairment with scopolamine (2 mg/kg BW), animals underwent behavioral evaluations on Y- and radial mazes. As results, age and ovariectomy did not induce significant changes in the reference memory errors. While age decreased working memory errors, ovariectomy increased it. The MC as well as F. umbellata extract significantly increased (p<0.01) the percentage of spontaneous alternation and decreased (p<0.001) working and spatial reference memory errors and anxiety parameters (rearing and grooming) in ovariectomized rats. MC significantly reduced (p<0.05) the MDA level, but resulted in an increase in GSH level in brain homogenates. These results suggest that MC is endowed with neuroprotective effects and could account for the neuroprotective effects of F. umbellata in rats

Evaluation of the estrogenic properties of aqueous extracts of Tragia benthamii Baker (Euphorbiaceae) and Graptophyllum pictum (Acanthaceae) and their ability to alleviate some menopausal symptoms induced by ovariectomy in Wistar rats

Tragia benthamii Baker (Euphorbiaceae) and Graptophyllum pictum Linn (Acanthaceae) are two Cameroonian medicinal plants traditionally used against female reproductive tract disorders, during and after the reproductive period, and as an abortifacient. Since there were no scientific data supporting the above claims and pharmacological studies characterizing their estrogenic properties, we therefore aimed to evaluate their ability to induce estrogen-like effects on primary estrogens targets, uterine, vagina and mammary gland; as well as their ability to alleviate hot flushes in ovariectomized adult rats. For this purpose, we applied a 3-day uterotrophic assay to determine the estrogenic effects of each extract and the mixture of both plants as used by traditional practitioners. The extracts were administered orally for 3 days to the 10 to 12 weeks aged ovariectomized rats. The results obtained showed that the aqueous extract of T. benthamii at the dose of 500 mg / kg BW, the aqueous extract of G. pictum at all the tested doses as well as the aqueous extract of the mixture  at 275 mg / kg body weight induced a significant increase (p ˂ 0.01) of the uterine epithelium thickness. In addition, the aqueous extract of T. benthamii at the dose of 500 mg / kg BW, as well as the aqueous extract of the mixture at the doses of 50 and 275 mg / kg induced acinar development and eosinophil secretions. These results are proof of estrogen-like effects of T. benthamii and G. pictum and therefore justify the traditional use of these plants. This suggests the presence in these plants, of secondary metabolites with estrogenic properties, can induce cell proliferation, and to correct disorders of post-oophorectomy œstrogénopénia in the Wistar rats and therefore menopausal disorders

Antidiabetic properties of the methanolic extract of Bridelia grandis (Euphorbiacae) in ob/ob and db/db mice

Bridelia grandis is used in most parts of tropical Africa for the treatment of diabetes. The anti-diabetic properties of the methanolic stem bark extract of this plant was studied in ob/ob and db/db mice. The plant extract induced hypoglycaemic effects of long duration in the ob/ob mice, while its effects were less pronounced in the db/db mice. Twenty four hours after the cessation of drug administration, both ob/ob and db/db extract treated animals still had significantly lower fasting blood sugar levels when compared to controls, thus confirming its antidiabetic properties.Key words: Bridelia grandis (Euphorbiaceae), antidiabetic properties, ob/ob and db/db mice

Estrogenic properties of naturally occurring prenylated isoflavones in U2OS human osteosarcoma cells: Structure-activity relationships

Eight isoflavones derivatives, with isoprenyl and/or 7-methoxy substitution, isolated from Erythrina poeppigiana (Fabaceae) have been investigated for their estrogenic properties in receptor subtype-specific reporter gene assays. First we focused on their estrogen receptor alpha and beta (ERα and ERβ) selectivity, second we addressed structure-activity relationships, using bone-derived human osteosarcoma cell line (U2OS cells) stably expressing ERα or transiently expressing ERβ. Our results show that a substitution at position 3&apos; together with a 7-methoxy substitution on the genistein skeleton is associated with a statistically significant activation of the ERα- and ERβ-dependent reporter gene expression in U2OS cells starting from 0.1. nM. Particularly, the 7-methoxy-3&apos;-isoprenyl (1) and the 7-methoxy-3&apos;-(3-methyl-2-hydroxybuten-3-yl) (3) derivatives of genistein induces an ERα- and ERβ-coupled luciferase activity at a concentration ten times lower than that of genistein, for which a statistically significant effect was observable at 1. nM. On the other hand, isoprenyl substitution at position 6 of the A ring, compound 5, seems to have very little impact on the genistein ability to induce ER-coupled luciferase activity in U2OS cells, while a double prenylation at positions 8 and 3&apos;, compound 7, is associated with an almost complete loss of function on the reporter gene activation in U2OS-ERα, but in ERβ expressing system the effectiveness remains on a statistically significant level, demonstrating an &quot; exclusive ERβ-selectivity&quot; in U2OS human osteosarcoma cells, and therefore 7 can be considered as an isotype-selective ER ligand. Finally all the tested isoflavones derivatives appear to exhibit a slightly pronounced ERβ preference, depending upon the position and the nature of the substituent moiety on the isoflavone skeleton. The estrogen-like effect of these prenylated isoflavone derivatives could be inhibited by the pure ER antagonist ICI 182 780, indicating that these effects were primarily mediated through ERs. © 2010 Elsevier Ltd