In vitro and in vivo antiestrogenic effects of dichloromethane-methanol extract of Crateva adansonii DC

Abstract: Despite significant developments occurring in the treatment of cancer, it still remains the second deadly disease, responsible for 8.2 million deaths every year. Various natural substances have been studied for active molecules of tumor suppression in the past and the tropical flora, by its diversity, continues to provide new antitumor drugs. Crateva adansonii dichloromethane-methanol (DCM/MeOH) extract was previously reported to prevent breast tumors in Wistar rats. However, it exhibited weak cytotoxic effect in human MCF-7 cells. The present study, therefore, deals with the investigation of its estrogenic and antiestrogenic effects. In vitro estrogenicity and antiestrogenicity of C. adansonii DCM/MeOH extract were performed by E-screen assay. In vivo, the investigation was carried out using the 3 days uterotrophic assay in ovariectomized rats, a classical tool for the prediction of estrogenicity of chemicals. As a result, C. adansonii extract did not induce MCF-7 cells proliferation, which is an estrogenic hallmark. However, C. adansonii extract induced a significant (P <0.05) decrease in a concentration-dependent manner of the MCF-7 proliferation when co-administered with E2B. In vivo, no estrogen-like effect was observed following a 3-day treatment with C. adansonii extract in estrogen target organs. However, the co-administration of C. adansonii extract with E2V lead to decreased uterine wet weight (P <0.05), total protein levels in uteri (P <0.01) as well as uterine and vaginal epithelial heights (P <0.05) as compared to animals treated with E2V only. These results suggest that C. adansonii has antiestrogenic effects but not estrogenic effects, which might account for its previously observed antimammary tumour effects 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

Duguetia confinis Engl. &amp; Diels (Annonaceae) inhibitory and cytotoxic effects on breast adenocarcinoma growth both in vitro and in vivo

Background: Breast cancer is ranked as the most common malignant tumor in women globally with ∼ 2.3 million new cases (11.7 %) diagnosed in 2020. The multiple drawbacks associated with treatments, prompt researchers and patients to search for alternative therapy. Plants continue to offer encouraging leads, in particular those of the Annonaceae family, to which belongs Duguetia confinis, used by Cameroonian traditional healers to fight cancers. This study was aimed at investigating the effect of Duguetia confinis against human breast cancer cells. This was carried out by investigating the cytotoxicity, underlying mechanism of action and chemopreventive potential of D. confinis on 7,12-dimethylbenz(a)anthracene (DMBA)-induced breast cancer. Methods: To achieve this goal, the ethanolic extract of the bark of D. confinis was prepared and assayed for its ability to inhibit cell growth, cell proliferation and clone formation. Furthermore, cell death mechanisms, cell cycle progression and anti-metastatic potential were investigated. The in vivo study consisted in a once-off administration of 50 mg/kg BW DMBA (in olive oil, s.c) from the 10th day after pretreatment with D. confinis extract (50 and 100 mg/kg BW) or standards [tamoxifen (3.3 mg/kg) and letrozole (1 mg/kg)] or leaf extract of Annona muricata L. (200 mg/kg as pharmacological control). Normal and negative controls received vehicle (3 % ethanol). The treatment of animals was done for 20 weeks, followed by the assessment of the incidence, burden and volume of tumors, breast cancer biomarker (CA 15-3), antioxidant status, inflammatory status and histopathology profile. The LD50 of D. confinis extract was estimated according to OECD guideline 423. Results: D. confinis displayed cytotoxicity at 80 μg/mL on all the tested breast cancer cell lines. It induced apoptosis and caused a blockade at G0/G1; S-phase of MDA-MB 231 cells, thus, suggesting anticancer potential. A significant concentration-dependent antimetastatic potential was observed with D. confinis extract at 50 (p < 0.05) and 100 (p < 0.01) μg/mL, evidenced by a reduction in cell migration, chemotaxis and increased adhesion to extracellular matrix. With respect to the chemopreventive study, D. confinis was able to prevent the onset of breast adenocarcinoma in Wistar rats by preventing the growth of tumor mass and volume, as well as the histopathological severity of the disease. This was achieved through the modulation of antioxidant parameters (SOD, CAT, MDA) and inflammatory parameters (IL-12, IL-6, INF- gamma, TNF). Also, the LD50 of D. confinis extract was greater than 2000 mg/kg, indicating low acute toxicity and thus, favorable for therapeutic use. Conclusion: In summary, this study outlines for the first time the beneficial effect of D. confinis as a plant candidate in the fight against breast cancer just like other species of the Annonaceae family. However, further research studies are still warranted regarding its bioactive components, and in depth investigation of its anticancer mechanism of action are also needed

Dietary Plants for the Prevention and Management of Kidney Stones: Preclinical and Clinical Evidence and Molecular Mechanisms

Kidney stones are one of the oldest known and common diseases in the urinary tract system. Various human studies have suggested that diets with a higher intake of vegetables and fruits play a role in the prevention of kidney stones. In this review, we have provided an overview of these dietary plants, their main chemical constituents, and their possible mechanisms of action. Camellia sinensis (green tea), Rubus idaeus (raspberry), Rubia cordifolia (common madder), Petroselinum crispum (parsley), Punica granatum (pomegranate), Pistacia lentiscus (mastic), Solanum xanthocarpum (yellow-fruit nightshade), Urtica dioica (stinging nettle), Dolichos biflorus (horse gram), Ammi visnaga (khella), Nigella sativa (black-cumin), Hibiscus sabdariffa (roselle), and Origanum vulgare (oregano) have received considerable interest based on scientific evidence. Beside these dietary plants, phytochemicals—such as catechin, epicatechin, epigallocatechin-3-gallate, diosmin, rutin, quercetin, hyperoside, and curcumin—as antioxidant dietary phyto-phenols were found to be effective for the prevention of urolithiasis (the process of stone formation in the urinary tract). The main underlying mechanisms of these dietary plants and their isolated phytonutrients in the management of urolithiasis include diuretic, antispasmodic, and antioxidant activity, as well as an inhibitory effect on crystallization, nucleation, and aggregation of crystals. The results as presented in this review demonstrate the promising role of dietary plants and phytophenols in the prevention and management of kidney stones. Further investigations are required to confirm the safety and efficacy of these compounds

Correction to: Ficus sycomorus extract reversed behavioral impairment and brain oxidative stress induced by unpredictable chronic mild stress in rats

Correction After the publication of this article [1] it came to our attention that Harquin Simplice Foyet was incorrectly included as Harquin Simplice Harquin Foyet. The corrected name is included in the author list. The original article was updated

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

Cucumis sativus (Curcubitaceae) inhibits prostate carcinoma cell growth and prevents the testosterone-induced benign prostatic hyperplasia in Wistar rat

Pumpkin seeds are claimed to treat prostate tumour/cancer. The in vitro (ability to inhibit cell growth through MTT assay) and in vivo (ability to prevent testosterone-induced BPH in rats at the doses of 125, 250, 500 and 1000 mg/kg BW) of six edible pumpkin seeds found in Cameroonian were assessed. The endpoints were cell growth arrest, prostate mass and volume, prostatic epithelium height, prostatic proteins, prostate specific antigen (PSA) and inflammatory cytokines. In vitro, C. sativus seeds exhibited the most potent antiproliferative effects on DU145 and PC3 prostate cancer cells and its oil conserved almost all the effects of raw seeds. Further, it prevented the increased of prostate relative mass and volume, prostate epithelium height, PSA and testosterone dose-dependently compared to normal rats. This effect is thought to be mediated through antiandrogenic, estrogenic and anti-inflammatory activities, evidenced by a decreased in IL-1β, IL-6 and TNFα level. Overall, this results justify its traditional use

<em>In vitro</em> and <em>in vivo</em> antiestrogenic effects of dichloromethane-methanol extract<em> </em>of<em> Crateva adansonii</em> DC.

795-802Despite significant developments in the treatment of cancer, it still remains the second deadly disease, responsible for 8.2 million deaths every year. Various natural substances have been studied for active molecules of tumor suppression in the past, and the tropical flora, by its diversity, continues to provide new antitumor drugs. Crateva adansonii (the sacred barna) dichloromethane-methanol (DCM-MeOH) extract was previously reported to prevent breast tumors in Wistar rats. However, it exhibited weak cytotoxic effect in human MCF-7 cells. The present study, therefore, deals with the investigation of its estrogenic and antiestrogenic effects. In vitro estrogenicity and antiestrogenicity of C. adansonii DCM-MeOH extract were performed by E-screen assay. In vivo, the investigation was carried out using the 3-day uterotrophic assay in ovariectomized rats, a classical tool for prediction of estrogenicity of chemicals. As a result, C. adansonii extract did not induce MCF-7 cells proliferation, which is an estrogenic hallmark. However, C. adansonii extract induced a significant (P In vivo, no estrogen-like effect was observed following a 3-day treatment with C. adansonii extract in estrogen target organs. However, the co-administration of C. adansonii extract with E2V lead to decreased uterine wet weight (P P P C. adansonii has antiestrogenic effects but not estrogenic effects, which might account for its previously observed antimammary tumour effects in rats

Safety assessment of the methanol extract of the stem bark of Amphimas pterocarpoides Harms: Acute and subchronic oral toxicity studies in Wistar rats

Amphimas pterocarpoides Harms (Leguminosae) is widely used traditionally in Central and West Africa for the treatment of various ailments. However, no data regarding its safety have been published until now. Thus, the present study aimed to investigate the potential toxicity of the methanol extract of the stem bark of Amphimas pterocarpoides (AP) in Wistar rats following the OECD guidelines. In acute oral toxicity, female rats received a single dose of 2000 mg/kg of AP and were observed for 14 days. In subchronic toxicity, doses of 150, 300, 600 mg/kg/day of AP were given per os to rats (males and females) for 28 days. No death and abnormal behaviors were observed in acute toxicity and the LD50 was estimated higher than 5000 mg/kg. In the subchronic study, AP induced no significant variation in body weight and relative weight of organs, whereas a delayed decrease of white blood cell count and granulocytes was observed. Inconsistent increase of the total cholesterol/high density lipoprotein was observed at 600 mg/kg in males. Such variation (not dose dependent) and without biological relevance indicate a wide margin of safety for the traditional use of AP