Dietary supplementation with seeds of Sesamum indicum L. (pedaliaceae) mitigates the 7,12-dimethylbenz(a)anthracene-induced breast tumor burden in rats.

OBJECTIVES: Sesamum indicum L. seeds; rich in zinc and lignans are endowed with antioxidant and immunomodulatory properties which attract research on their anticancer potential. Although many studies have reported the in vitro antitumor potential of S. indicum and its phytoconstituents, much is yet to be known about its in vivo effects. To fill this gap, the effects of dietary supplementation with seeds of S. indicum in 7,12-dimethylbenz(a)anthracene-exposed rats was assessed. METHODS: 42 rats aged 30-35 days were randomized into six groups (n=6) as follows: the normal (NOR) and negative (DMBA) control groups were fed with standard diet; the positive control group (DMBA + Zinc) was fed with standard diet supplemented with commercial zinc (0.01 %); the test groups were fed with standard diet supplemented with S. indicum seeds in different proportions (6.25 , 12.5 and 25 %). Breast cancer was induced by a single administration of DMBA (50 mg/kg BW, s.c.) diluted in corn oil. The experiment lasted 20 weeks and afterward, tumor incidence; tumor burden, tumor volume, tumor micro-architecture and some biochemical parameters were evaluated. RESULTS: As salient result, 100 % of rats in the DMBA group developed tumors, while rats feed with rat chow supplemented with S. indicum seeds (25 %) had a reduced incidence of tumors (33.3 %) and tumor volume (2.71 cm3 in sesame 25 % vs. 4.69 cm3 in the DMBA group, p˂0.01). The seeds (25 %) also slowed DMBA-induced neoplasm expansion in mammary ducts as compared to rats of DMBA group. CONCLUSIONS: In summary, supplementation with S. indicum seeds slowed breast tumorigenesis via its antioxidant capacity.

Aridanin and oleanane-3- O-ß-D-glucoside-2'-acetamide obtained from Tetrapleura tetraptera (Schumach. & Thonn) Taub. (Fabaceae) induces potent apoptotic activity in human prostate cancer cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Tetrapleura tetraptera (Schumach. and Thonn.) Taub. (Fabaceae) is a tropical plant that is used in Cameroon pharmacopeia for the treatment of many cancers including prostate cancer (PCa), which is a major cause of men's death worldwide. The objective of this study was to evaluate the anticancer properties as well as underlying mechanisms of isolates from T. tetraptera on DU145, PC3 and LNCaP cancer cell lines. MATERIALS AND METHODS: Eight (8) compounds were purified from T. tetraptera stem bark extract through silica gel column chromatography (CC) and characterized using spectroscopic techniques (1D and 2D NMR), HRESIMS. Cell growth was assessed by a well-characterized MTT assay, while BrdU and clonogenicity assays provided information on the cell proliferation index. Further, the impact of the compounds on cell cycle progression and cell death were performed through Flow cytometry. Cell adhesion, cell migration and chemotaxis along with some proteins of epithelial-mesenchymal transition (EMT) were assayed. RESULTS: Out of the eight (1-8) isolates from T. tetraptera only oleanane-3-O-ß-D-glucoside-2'-acetamide and aridanin showed potent cell growth arrest with an estimated CC50 of 15, 23, 16 and 17, 26, 16 µg/mL on DU145, PC3 and LNCaP cells, respectively. A 15% (DU145) and 25% (LNCaP) increase in apoptotic cells induced by oleanane-3-O-ß-D-glucoside-2'-acetamide and aridanin at 10 µg/mL were noticed. Oleanane-3-O-ß-D-glucoside-2'-acetamide and aridanin at 2.5 and 10 µg/mL reduced the number of cells in S-phase and raised cells in G2/M phase. At the same concentrations, they decreased the number of invading DU145 cells and increased the adherence of DU145 cells to fibronectin and collagen matrix at tested concentrations, accompanied by an increase in integrin ß-1 (10 µg/mL) and integrin ß-4 (2.5 µg/mL) expression. Furthermore, a down-regulation of pcdk1, cdk2, Bcl-2, N-Cad, vimentin and cytokeratine 8-18 was noticed while, p19, p27, p53 pAKT, Bax, caspase-3 and E-Cad were up-regulated. CONCLUSIONS: This study outlines for the first time, the anticancer ability of compounds oleanane-3-O-ß-D-glucoside-2'-acetamide (4) and aridanin (6) from Tetrapleura tetraptera and proposes their putative mechanisms of action.

Automated silylation of flavonoids using 3D printed microfluidics prior to chromatographic analysis: system development.

Flavonoids are a class of secondary plant metabolites with low molecular weights. Most flavonoids are highly polar and unsuitable for gas chromatographic analyses. Derivatization is commonly used to make them amenable to gas chromatography by altering their physicochemical properties. Although highly effective, derivatization techniques introduce extra preparation steps and often use hazardous chemicals. The aim of this study was to automate derivatization (specifically, silylation) by developing 3D printed microfluidic devices in which derivatization of flavonoids can occur. A microfluidic device was designed and 3D printed using clear polypropylene. Quercetin and other flavonoids (TED 13 and ZTF 1016) isolated from plant extracts were silylated with N-tert-butyldimethylsilyl-N-methyltrifluoroacetamide (MTBSTFA) at room temperature both in batch and in continuous flow. All the samples were analyzed using Fourier transform infrared (FTIR) spectroscopy, gas chromatography combined with mass spectrometry (GC-MS), and high-resolution accurate mass spectrometry (HR-MS). Interestingly, the HR-MS results showed that the flow method was about 25 times more efficient than the batch method for quercetin samples. The TED 13 flavonoid was completely derivatized in the flow method compared to the batch method where the reaction was incomplete. Similar results were observed for ZTF 1016, where the flow method resulted in a four times derivatized compound, while the compound was only derivatized once in batch. In conclusion, 3D printed microfluidic devices have been developed and used to demonstrate a semi-automated, inexpensive, and more efficient natural product derivatization method based on continuous flow chemistry as an alternative to the traditional batch method.

Effect of variety and malting conditions on proteolytic activity, free amino nitrogen, and soluble protein contents of two maize varieties (Atp-Y and Coca-sr): amylolytic activity and physico-chemical and functional properties of optimal sample.

Introduction: The utilization of sprouted meals in beer production and enhancing the physicochemical properties of supplementary foods is widespread in Africa. This work aimed to determine the influence of soaking, germination, maturation and variety conditions on the physicochemical properties, proteolytic activity, free amino nitrogen (FAN) and soluble protein contents of Coca-sr and Atp-Y maize varieties. Methods: To achieve this, the central composite design (CCD) was used for the optimization of five parameters, namely soaking time (18-42 h), plant salt concentration (0.5-1.2%), soaking temperature (25-41°C), sprouting time (80-195 h) and ripening time (17.50-42 h), and following dependent variables were investigated: proteolytic activity, FAN content and soluble protein. Optimal samples flours obtained were then subsequently subjected to physicochemical and functional analysis. Results: The analysis of results showed that the linear, interactive and quadratic effects of the factors significantly (p<0.05) affected the proteolytic activity, FAN and soluble protein contents of both varieties. The direction of each factor's variation and its effects were not similar in the two varieties. The optimal malting conditions were 7.31 h soaking with 1.678% vegetable salt at a temperature of 34.65°C followed by sprouting for 245.59 h and maturation for 0.765 h for the Atp-Y variety. For the Coca-sr variety, it requires 1.608 h of soaking with 1.678% vegetable salt at a temperature of 51.93°C followed by 273.94 h and 58.73 h for sprouting and ripening time respectively. The meals of Coca-sr produces using these optimal conditions showed a significantly (p<0.05) higher proteolytic activity, FAN and soluble protein content. The amylolytic activity was more pronounced in the Atp-Y variety, as was the content of essential amino acids. The above optimal conditions reduced the content of anti-nutrients (phytates, saponins, oxalates, condensed and hydrolysable tannins), improved the availability of minerals (Ca and Mg), reduced the pH, mass density, water retention capacity and swelling rate. Conclusion: As a result, the optimal flours of these two maize varieties could be applied in the formulation of supplementary foods, bakery products and beer by industrialists.

Estrogenic and anti-amnesic potential of Millettia griffoniana Baill. (Fabaceae) ethanolic extract on scopolamine-induced memory impairment in ovariectomized Wistar rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Dementias including Alzheimer disease (AD) are three times higher in menopausal women than in men. Phytoestrogens, a group of plant-derived compounds are known to alleviate menopausal complaints including dementia. Millettia griffoniana Baill is a phytoestrogen-rich plant used to treat menopausal complaints and dementia. AIM: Evaluating the estrogenic and neuroprotective potential of Millettia griffoniana on ovariectomized (OVX) rats. MATERIALS AND METHODS: The in vitro safety of M. griffoniana ethanolic extract was assayed by MTT in human mammary epithelial (HMEC) and mouse neuronal (HT-22) cells and its lethal dose 50 (LD50) was estimated following OECD 423 guidelines. For estrogenicity, in vitro the well known E-screen assay on MCF-7 cells was performed and in vivo four groups of OVX rats were treated either with 75, 150 and 300 mg/kg M. griffoniana extract doses or estradiol (1 mg/kg BW) for three days; and changes in uterine and vagina were analyzed. Then, for neuroprotective effect, Alzheimer-type dementia induction was achieved by scopolamine (1.5 mg/kg B.W., i.p.) injection four days/week and M. griffoniana extract as well as piracetam (standard) were administered daily for 2 weeks to evaluate the extract's neuroprotective potential. The endpoints were the assessment of learning and working memory, oxidative stress state (SOD, CAT, and MDA) in brain, acetylcholine esterase (AChE) activity and the histopathological changes in hippocampus. RESULTS: No toxic effect was observed when incubating mammary (HMEC) and neuronal (HT-22) cells with M. griffoniana ethanol extract for 24 h and its LD50 was found >2000 mg/kg. The extract also exhibited both in vitro and in vivo estrogenic activities, displayed by a significant (p < 0.01) increment in MCF-7 cells population in vitro and an increase in the epithelium height of the vagina and the wet weight of the uterus mainly with the 150 mg/kg BW extract dose compared to untreated OVX rats. The extract also reversed scopolamine-induced memory impairment in rat by improving learning, working and reference memory. This was associated with an increment in CAT and SOD expression, alongside a decrement in MDA content and AChE activity in hippocampus. Further, the extract reduced neuronal cell loss in hippocampal structures (CA1, CA3 and dentate gyrus). High Performance Liquid Chromatography coupled with Mass Spectrometry (HPLC-MS) spectra, revealed the presence of numerous phytoestrogens in M. griffoniana extract. CONCLUSION: M. griffoniana ethanolic extract has estrogenic, anticholinesterase and antioxidant activities that could account for its anti-amnesic effects. These findings therefore sheds light on why this plant is commonly used in the therapy of menopausal complaints and dementia.

Ethnopharmacological Study of Medicinal Plants Used for the Treatment of Cardiovascular Diseases and Their Associated Risk Factors in sub-Saharan Africa.

Cardiovascular diseases (CVDs) are the leading cause of global mortality, including deaths arising from non-communicable diseases in sub-Saharan Africa (SSA). Consequently, this study aimed to provide details of medicinal plants (MPs) employed in SSA for the treatment of CVDs and their related risk factors to open new avenues for the discovery of novel drugs. The extensive ethnopharmacological literature survey of these MPs in 41 SSA countries was based on studies from 1982 to 2021. It revealed 1,085 MPs belonging to 218 botanical families, with Fabaceae (9.61%), Asteraceae (6.77%), Apocynaceae (3.93%), Lamiaceae (3.75%), and Rubiaceae (3.66%) being the most represented. Meanwhile, Allium sativum L., Persea americana Mill., Moringa oleifera Lam., Mangifera indica L., and Allium cepa L. are the five most utilised plant species. The preferred plant parts include the leaves (36%), roots (21%), barks (14%), fruits (7%), and seeds (5%), which are mostly prepared by decoction. Benin, Mauritius, Nigeria, South Africa, and Togo had the highest reported use while most of the investigations were on diabetes and hypertension. Despite the nutraceutical advantages of some of these MPs, their general toxicity potential calls for caution in their human long-term use. Overall, the study established the need for governments of SSA countries to validate the efficacy/safety of these MPs as well as provide affordable, accessible, and improved modern healthcare services.

Effects of Hibiscus sabdariffa Calyxes Aqueous Extract on Antioxidant Status and Histopathology in Mammary Tumor-Induced in Rats.

Breast cancer is a major threat worldwide. Hibiscus sabdariffa is widely consumed as beverage in sub-Saharan Africa for its anticancer potential. The present study therefore aimed at scientifically verifying its anticancer effect in rats. For this, 48 Wistar rats (∼55 days) were treated either with tamoxifen at 3.3 mg/kg BW (standard) or with a decoction of H. sabdariffa (125, 250, and 500 mg/kg BW) or distilled water (vehicle). Breast cancer was induced by a single dose of 50 mg/kg of 7,12-dimethylbenz(a)anthracene (DMBA). At the end of the 21 weeks of treatment, the tumor incidence, tumor morphology, histopathology, as well as some biochemical parameters in the tumors were assessed. As a result, 86% of DMBA's rats developed mammary tumors. The H. sabdariffa extract (125 and 250 mg/kg) reduced tumor incidence by 63% and 75%, respectively; inhibited tumor burden by 84.86% and 38.78%, respectively, and decreased tumor volume by more than 72% compared to the DMBA group. It also protected rats against DMBA-induced diffuse breast neoplasia, and the optimal effect was recorded at 125 mg/kg. Furthermore, it significantly increases the SOD activity and decreases the MDA level. In summary, H. sabdariffa has antibreast tumor and antioxidant properties in rats, which could justify its common use to treat cancer.

Chemical constituents from fruits of Cnestis ferruginea Vahl ex. DC (Connaraceae) and evaluation of their anticholinesterase and antiradical activities.

The phytochemical investigation of the DCM/MeOH (1:1) extract of the fruits of Cnestis ferruginea led to the isolation and characterization of one new quinic acid derivative, ferruginoic acid (1), together with six known compounds 2-7. Compounds 3-7 were reported for the first time from this species. The structures of compounds 1-7 were elucidated on the basis of 1 D and 2 D NMR spectroscopic data, mass spectrometry and by comparison of spectroscopic data with those from the literature. The anticholinesterase (AChE and BChE) activity and DPPH free radical scavenging assay of compounds 1, 3, 4 and 7 were evaluated. Ferruginoic acid (1) exhibited moderate anticholinesterase activity with IC50 value of 36.18 ± 1.78 µg/mL against AChE. Compounds 3, 4 and 7 showed high activity against free radical (DPPH•) scavenging assay (DPPH) with IC50 values 40.09 ± 0.96 µg/mL, 61.70 ± 0.78 µg/mL and 41.87 ± 0.62 µg/mL respectively. These results indicate that C. ferruginea and its constituents could be employed in the management of Alzheimer's disease.

Phytochemicals and Amino Acids Profiles of Selected sub-Saharan African Medicinal Plants' Parts Used for Cardiovascular Diseases' Treatment.

For years, the focus on the lipid-atherosclerosis relationship has limited the consideration of the possible contribution of other key dietary components, such as amino acids (AAs), to cardiovascular disease (CVD) development. Notwithstanding, the potential of plant-based diets, some AAs and phytochemicals to reduce CVDs' risk has been reported. Therefore, in this study, the phytochemical and AA profiles of different medicinal plants' (MPs) parts used for CVDs' treatment in sub-Saharan Africa were investigated. Fourier-transform infrared analysis confirmed the presence of hydroxyl, amino and other bioactive compounds' functional groups in the samples. In most of them, glutamic and aspartic acids were the most abundant AAs, while lysine was the most limiting. P. biglobosa leaf, had the richest total branched-chain AAs (BCAAs) level, followed by A. cepa bulb. However, A. cepa bulb had the highest total AAs content and an encouraging nutraceutical use for adults based on its amino acid score. Principal component analysis revealed no sharp distinction between the AAs composition of MPs that have found food applications and those only used medicinally. Overall, the presence of medicinally important phytochemicals and AAs levels in the selected MPs' parts support their use for CVDs treatment as they might not add to the AAs (e.g., the BCAAs) burden in the human body.

Anti-breast cancer potential of Anonidium mannii (Oliv.) Engl. & Diels barks ethanolic extract: UPLC-ESI-QTOF-MS detection of anticancer alkaloids.

ETHNOPHARMACOLOGICAL RELEVANCE: Breast cancer is a serious threat in low-income as well as developed countries. To face this, many herbal preparations are prescribed by traditional healers in Cameroon, among which is Anonidium mannii commonly called "wild soursop". AIM: This study was undertaken to assess the anti-tumor effect of A. mannii ethanolic extract on cancer cell growth and against DMBA-induced mammary tumors in rats. MATERIALS AND METHODS: The well characterized MTT bioassay was used to assess the cytotoxic potential of A. mannii ethanolic extract in liver (HepG2), prostate (DU145 & PC3) and breast (MCF-7) cancer cell lines. Considering the fact that breast cells were the most sensitive to the extract, a 7,12-dimethylbenz(a)anthracene (DMBA)-induced breast tumor rat model was used to assess the possible anticancer effect of A. mannii extract. Indeed, rats were treated with either tamoxifen (3.3 mg/kg BW) or A. mannii extract (16.5, 50 and 150 mg/kg BW) or vehicle (2% ethanol) for 20 weeks. Tumor incidence, tumor mass and volume, oxidative stress status in tumor as well as tumor histoarchitecture were evaluated. RESULTS: A 24 h incubation of tested cells with the A. mannii extract significantly slowed cell growth in a concentration-dependent manner with an interesting effect in breast cells (IC50 ~61.5 µg/mL). As compared to the DMBA rats, those treated with A. mannii extract (50 and 150 mg/kg) showed reduced breast tumor incidence (28%), tumor burden (95.34% at 50 mg/kg and 99.14% at 150 mg/kg) and tumor volume (~92%). A. mannii extract counteracted the high proliferation of terminal mammary ducts induced by DMBA, mainly at 50 mg/kg. Furthermore, the extract decreased MDA and nitrite levels but increased SOD activity in the mammary gland. High Performance Liquid Chromatography coupled with Mass Spectrometry (HPLC-MS) analysis detected potential anticancer and antioxidant alkaloids in A. manni extract, which are close to those found in Annona muricata. CONCLUSION: These results provide evidence on the in vitro and in vivo anticancer effects of A. mannii, and therefore support its use in traditional medicine system to fight against cancer.

Regular consumption of "Nkui", a Cameroonian traditional dish, may protect against cardiovascular and bone disorders in an estrogen deficiency condition.

OBJECTIVES: There is a growing body of evidence indicating the potential of culinary herbs and spices to decrease the incidence of several chronic diseases or conditions. Because of this, the WHO recommends their regular consumption. In the Cameroonian culinary practices, "Nkui" is a famous dish made from a mixture of 10 spices. In our previous study, the ethanolic extract of this mixture exhibited promising estrogenic properties. Thus, this study aimed to evaluate its protective effects on some menopause-related cardiovascular and bone disorders. METHODS: For this purpose, a post-menopause-like model (ovariectomized rats) has been used. Animals were orally treated with the "Nkui" extract for 60 days. The investigation focused on the oxidative stress status, endothelial function (NO bioavailability), lipid profile, and bone mass, biochemical (calcium and inorganic phosphorus contents, serum alkaline phosphatase activity) and histomorphological features. RESULTS: The extract regulated lipid metabolism in a way to prevent accumulation of abdominal fat, gain in body weight and increased atherogenic indexes induced by ovariectomy. It prevented menopause-related low levels of nitric oxide and oxidative stress damage by increasing superoxide dismutase and catalase activities, while reducing glutathione and malondialdehyde levels in the heart and aorta. Moreover, it prevented ovariectomy-induced bone mass loss, bone marrow disparities and the disorganization of the trabecular network. It also increased femur calcium and inorganic phosphorus contents. CONCLUSIONS: These results suggest that a regular consumption of "Nkui" may have health benefits on cardiovascular system and osteoporosis, major health issues associated with menopause.

Elemental measurements and health risk assessment of sub-Saharan African medicinal plants used for cardiovascular diseases' and related risk factors' treatment.

BACKGROUND: Dietary factors have been noted to influence the development of cardiovascular diseases (CVDs) which are the number one global cause of death. In this study, the nutritional importance and human health risk of the minerals composition of 20 medicinal plants' (MPs) parts used for treating CVDs and related risk factors in sub-Saharan Africa (SSA) were assessed. METHODS: Inductively coupled plasma technology was used for determining the minerals composition of the MPs while human health risk assessment was based on hazard quotients, hazard indexes and non-carcinogenic risk analysis of the studied heavy metals. RESULTS: The investigation showed varied level of minerals in the studied MPs' parts with K having the highest concentration in most. Although level of some elements inM. lucida, V. amygdalina leaves, T. cacao seed and Z. officinale rhizome revealed their possibility in preventing the occurrence of atherosclerosis, unsafe levels of some trace elements were recorded in M. lucida and V. amygdalina leaves. V. amygdalina leaves and A. cepa bulb also had their Pb contents higher than the WHO/FAO Codex permitted maximum level for leafy and bulb vegetables, respectively. In spite of the desirable Na/K and Zn/Cu ratios in all the tested MPs with their Cd and Pb levels below the WHO recommended maximum levels for dried medicinal plant materials, health risk assessment showed that habitual use of almost all of the studied MPs would present an unacceptable risk of non-carcinogenic effects on health. With the exception of S. aromaticum flower bud and T. tetraptera fruit, principal component and hierarchical cluster analyses of other plants' parts (MPs' parts aside from the leaves) analysed provided a distinction between MPs which have found food applications and those solely used for medicinal purposes. CONCLUSIONS: The study revealed that type of MP, plants' part, maturity stage, agricultural practice, growing environment and conditions, are among the factors determining the safety of plant materials used for CVDs' and related risk factors' treatment in SSA. To protect the lives of CVDs patients who rely on traditional medicine for treatment, government of SSA countries and relevant authorities need to set a regulatory limit for maximum acceptable concentration of minerals in MPs used in the region. Assessment of the physicochemical properties and pollution level of soil used for cultivation of these MPs is also encouraged.

The antimammary tumor effects of ethanolic extract of propolis from Adamawa region (Cameroon) are by apoptosis via reactive oxygen species-mediated mitochondrial pathway.

Identification of novel natural treatment to combat cancer is a current need. This study was aimed at assessing the anticancer effects of ethanol-extracted Cameroonian propolis (EEP). The antitumor effect of EPP was evaluated in vitro by measuring; cell viability, cell cycle, cell death mechanism, cell migration/invasion, reactive oxygen species (ROS), mitochondrial potential (ΔΨm), caspase activity, and apoptosis-regulating proteins (Bcl-2 and Bcl-XL) in cell lines. In vivo, the effect of EEP against 7,12 dimethylbenz(a)anthracene (DMBA)-induced breast tumorigenesis in rats was assessed. EEP was found to induce cytotoxicity against ER negative MDA-MB-231 breast cancer cells by activating apoptosis through ROS-mediated mitochondrial pathway. The extract equally triggered caspase-3 and caspase-9, increment of ROS level, disruption of ΔΨm and down-regulation of Bcl-XL and Bcl-2 proteins. Besides, EPP prevented migration and invasion activities by inhibiting MMP-2 activity. At all doses it prevented breast tumor incidence (20% in EEP 150 mg/kg vs 70% in DMBA) as well as tumor burden. Tumor sections from EEP-treated rats showed middle proliferation of mammary ducts with weak inflammatory responses. In summary, Cameroonian propolis exhibited antimammary tumor effects via the intrinsic pathway of apoptosis.

Abyssinone V-4' Methyl Ether, a Flavanone Isolated from Erythrina droogmansiana, Exhibits Cytotoxic Effects on Human Breast Cancer Cells by Induction of Apoptosis and Suppression of Invasion.

Abyssinone V-4' methyl ether (AVME) isolated from Erythrina droogmansiana was recently reported to exhibit anti-mammary tumor effect in mice. The present work was therefore aimed at elucidating its cellular and molecular mechanisms. To achieve our goal, the cytotoxicity of AVME against tumoral and non-tumoral cell lines was evaluated by resazurin reduction test; flow cytometry allowed us to evaluate the cell cycle and mechanisms of cell death; the mitochondrial transmembrane potential, reactive oxygen species (ROS) levels, and caspase activities as well as apoptosis-regulatory proteins (Bcl-2 and Bcl-XL) were measured in MDA-MB-231 cells. Further, the antimetastatic potential of AVME was evaluated by invasion assay. AVME exhibited cytotoxic effects in all tested tumor cell lines and induced a significant increase in the percentage of MDA-MB-231 cells at G2/M and S phases of the cell cycle in a concentration-dependent manner. AVME also induced apoptosis in MDA-MB-231 cells, which was accompanied by the activation of caspase-3 and caspase-9 and downregulation of Bcl-2 and Bcl-XL proteins. Moreover, AVME suppressed cancer cell invasion by the inhibition of the metalloproteinase-9 activity. Findings from this study suggest that AVME has anti-breast cancer activities expressed through mitochondrial proapoptotic pathway including impairment of aggressive behaviors of breast cancer cells.

Synthesis of gold nanoparticles using Crinum macowanii bulb extracts and the application of these materials in blood detections at crime scenes.

We here in report the synthesis of gold nanoparticles (AuNPs) using a Crinum macowanii bulb water extract. The as-synthesized AuNPs were characterized using ultraviolet-visible spectroscopy, Fourier transform infrared spectroscopy, X-ray diffraction, transmission electron microscopy, and a zeta potential-sizer. The results showed that the as-synthesized AuNPs were crystalline and mostly spherical in shape with a small mixture of triangular, tetrahedral, hexagonal, octagonal, and diamond shapes. The as-synthesized AuNPs together with those synthesized by conventional methods were subsequently used as enhancers for the luminol signal in blood detection. It was noted that the AuNPs synthesized from the Crinum macowanii bulb water extract could enhance the chemiluminescence signal for blood detection by luminol to the same extent as AuNPs prepared by conventional methods. Furthermore, both types of AuNPs served as fluorescence enhancers for blood detection when luminol was replaced with the bulb water extract.

Bioguided identification of daucosterol, a compound that contributes to the cytotoxicity effects of Crateva adansonii DC (capparaceae) to prostate cancer cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Crateva adansonii DC (Capparaceae) is a shrub used to treat tumors in Cameroon. In our previous reports, a Crateva adansonii dichloromethane-methanol (DCM/MeOH) extract was shown to prevent chemically induced tumors in Wistar rats. AIM OF STUDY: To determine the bioactive principle of Crateva adansonii extract and to elucidate its underlying mechanism. MATERIALS AND METHODS: An activity-guided fractionation was realized using MTT assay. To investigate if the bioactive compound daucosterol (CA2) accounted for the previously observed anticancer effects of the C. adansonii extract, it was tested on cell growth, cell proliferation, cell cycle, cell death mechanism and cell migration. In addition, cell cycle- and apoptosis-regulating proteins were assessed by Western blotting. RESULTS: Daucosterol (CA2), a steroid saponin, was identified as major anticancer principle of the C. adansonii extract. Daucosterol significantly inhibited LNCaP, DU145 and PC3 prostate carcinoma cell growth and proliferation at the optimal concentration of 1 µg/mL. It also significantly increased the number of late apoptotic (DU145) and apoptotic (PC3) cells. The number of cells in S phase increased in DU145, while the number of G0/G1 cells decreased. Cell cycle proteins (cdk1, pcdk1, cyclin A and B) were down-regulated in DU145 and PC3 cells, whereas only cdk2 was down-regulated in PC3 cells. Moreover, the anti-apoptotic Akt, pAKT and Bcl-2 proteins were down-regulated, while the pro-apoptotic protein Bax was up-regulated. CA2 induced anti-metastatic effects by decreasing chemotaxis and cell migration, while it increased cell adhesion to fibronectin and collagen matrix. CONCLUSION: These results suggest that daucosterol is the major active principle responsible at least in part for the anticancer effect of the extract of Crateva adansonii.

Anthonotha macrophylla P. Beauv (Caesalpiniaceae) aqueous extract exhibits antiestrogenic effects in vitro and in vivo.

Background Phytoestrogens are natural compounds known as natural selective estrogen receptor modulators used as alternatives against estrogen-dependent cancers. This study aims to evaluate the antiestrogenic effects of Anthonotha macrophylla, a plant used to treat cancer in Cameroon. Methods The estrogenic/antiestrogenic activities of A. macrophylla aqueous extract were evaluated in vitro using MCF-7 cell proliferation assay. Moreover, a classical uterotrophic test was carried out to evaluate the antiestrogenic effects of A. macrophylla in rats. Changes in the uterus, vagina, and mammary glands were used as endpoints of estrogenicity. Results Anthonotha macrophylla induced antiestrogenic effects in vitro at all the tested concentrations by inhibiting estradiol-induced MCF-7 cell proliferation (p < 0.001). In vivo, a coadministration of estradiol with A. macrophylla extract led to the decrease of uterine [150 (p < 0.05) and 300 (p < 0.01) mg/kg body weight (BW)] and vaginal [75 (p < 0.01) and 300 (p < 0.05) mg/kg BW] epithelial thickness. In addition, a reduction in the mammary gland acini lumen's diameter was also observed at 75 and 150 mg/kg. Gas chromatography-time-of-flight-mass spectrometry analysis showed that phenolic acid derivatives are present in A. macrophylla extract, which are well known to be endowed with estrogenic/antiestrogenic properties. The LD50 of A. macrophylla was estimated to be less than 2000 mg/kg. Conclusions Anthonotha macrophylla aqueous extract has antiestrogenic properties. This could promote more studies to explore its ability to prevent estrogen-dependent cancers.

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.

The hydro-ethanolic extract of Acacia seyal (Mimosaceae) stem barks induced death in an ER-negative breast cancer cell line by the intrinsic pathway of apoptosis and inhibited cell migration.

BACKGROUND: Despite the 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. Acacia seyal is a plant used in Cameroonian traditional system to treat cancer. It exhibited cytotoxic effects towards human breast adenocarcinoma cells. The present work was therefore designed to elucidate the underlying mechanisms by which A. seyal extract induced its cytotoxic effect. METHODS: The cell death mechanism (apoptosis or necrosis) and cell cycle analyses were assessed using flow cytometry. The levels of reactive oxygen species (ROS), mitochondrial membrane potential (ΔΨm), caspases activities as well as Bcl-2 and Bcl-xL protein contents were assessed in MDA-MB-231 cells. Afterwards, cell migration/invasion was also assessed. RESULTS: The A. seyal extract induced apoptosis in MDA-MB-231 cells, while it failed to do so in MCF-7 cells. It induced cell cycle arrest in G2/M phase. Further it induced a decrease in ΔΨm, an increase in ROS levels and caspases activities as well as a down regulation in Bcl-2 and Bcl-xL protein contents in MDA-MB-231 cells. Moreover, A. seyal extract exhibited anti-migration, anti-invasion activities in MDA-MB-231 cells. CONCLUSION: These results demonstrate that A. seyal extract induced its antitumor effects mainly by interference in metastasis related events, by triggering apoptosis through a ROS-mediated mitochondrial pathway.

Synthesis of silver nanoparticles from a Desmodium adscendens extract and its antibacterial evaluation on wound dressing material.

The one-pot synthesis of silver nanoparticles (AgNPs) using the medium-polar extract of Desmodium adscendens (Sw.) DC. is presented here as an alternative synthesis of metal NPs. Characterisation of the formed NPs showed polydispersed AgNPs ranging from 15 to 100 nm where the concentration of metal ions was found to play a role in the size and shape of the prepared NPs. It could be established that the flavonoids, saponins, and alkaloids present in the extract acted as both reducing and stabilising agents during the formation of the capped metal NPs. This means of NP synthesis was also employed during the in situ immobilisation of AgNPs on gauze and plaster. An evaluation of the antibacterial activity of the medium-polar D. adscendens extract, AgNPs suspended in solution, and the immobilised AgNPs against Staphylococcus aureus (ATCC 25923), Bacillus cereus (ATCC 11778), and Escherichia coli (ATCC 25922) showed high efficacy against the latter in particular. This suggests that gauze, dilute silver nitrate solutions, and D. adscendens extract could be used successfully in the simple in situ preparation of effective antibacterial wound dressings.