Antibacterial Activities of Selected Cameroonian Plants and Their Synergistic Effects with Antibiotics against Bacteria Expressing MDR Phenotypes

The present work was designed to assess the antibacterial properties of the methanol extracts of some Cameroonian medicinal plants and the effect of their associations with currently used antibiotics on multidrug resistant (MDR) Gram-negative bacteria overexpressing active efflux pumps. The antibacterial activities of twelve methanol extracts of medicinal plants were evaluated using broth microdilution. The results of this test showed that three extracts Garcinia lucida with the minimal inhibitory concentrations (MIC) varying from 128 to 512 μg/mL, Garcinia kola (MIC of 256 to 1024 μg/mL), and Picralima nitida (MIC of 128 to 1024 μg/mL) were active on all the twenty-nine studied bacteria including MDR phenotypes. The association of phenylalanine arginine β-naphthylamide (PAβN or efflux pumps inhibitor) to different extracts did not modify their activities. At the concentration of MIC/2 and MIC/5, the extracts of P. nitida and G. kola improved the antibacterial activities of some commonly used antibiotics suggesting their synergistic effects with the tested antibiotics. The results of this study suggest that the tested plant extracts and mostly those from P. nitida, G. lucida and G. kola could be used alone or in association with common antibiotics in the fight of bacterial infections involving MDR strains

Antibacterial activities of selected edible plants extracts against multidrug-resistant Gram-negative bacteria

BACKGROUND: In response to the propagation of bacteria resistant to many antibiotics also called multi-drug resistant (MDR) bacteria, the discovery of new and more efficient antibacterial agents is primordial. The present study was aimed at evaluating the antibacterial activities of seven Cameroonian dietary plants (Adansonia digitata, Aframomum alboviolaceum, Aframomum polyanthum, Anonidium. mannii, Hibiscus sabdarifa, Ocimum gratissimum and Tamarindus indica). METHODS: The phytochemical screening of the studied extracts was performed using described methods whilst the liquid broth micro dilution was used for all antimicrobial assays against 27 Gram-negative bacteria. RESULTS: The results of the phytochemical tests indicate that all tested extracts contained phenols and triterpenes, other classes of chemicals being selectively present. The studied extracts displayed various degrees of antibacterial activities. The extracts of A. digitata, H. sabdarifa, A. polyanthum, A. alboviolaceum and O. gratissimum showed the best spectra of activity, their inhibitory effects being recorded against 81.48%, 66.66%, 62.96%, 55.55%, and 55.55% of the 27 tested bacteria respectively. The extract of A. polyanthum was very active against E. aerogenes EA294 with the lowest recorded minimal inhibitory concentration (MIC) of 32 μg/ml. CONCLUSION: The results of the present work provide useful baseline information for the potential use of the studied edible plants in the fight against both sensitive and MDR phenotypes

Phytochemical analysis and antibiotic-modulating activity of Cocos nucifera, Glycine max and Musa sapientum methanol extracts against multidrug resistant Gram-negative bacteria

Background: The rapid emergence of multidrug resistant (MDR) bacteria is occurring worldwide, endangering the efficacy of antibiotics, which have transformed medicine and saved millions of lives. Antibiotic-resistant infections are already widespread in the Sub-Saharan Africa and across the globe. To extend the search for new and more efficient antimicrobial drugs from natural sources, this work has been carried out to study the phytochemical composition and the antibacterial activities of some Cameroonian dietary plants (Cocos nucifera, Glycine max and Musa sapientum) against several MDR Gram-negative strains including Escherichia coli, Enterobacter aerogenes, Providencia stuartii, Klebsiella pneumoniae, Pseudomonas aeruginosa species expressing efflux pumps.Methods: Phytochemical screening of plant extracts was performed using qualitative standard methods and the antimicrobial assays of these extracts alone and in combination with antibiotics were done using serial 96-wells microplate dilution essays.Results: Each plant extract contained at least three mean classes of secondary metabolites. Glycine max, epicarps, leaves and bark of C. nucifera as well as mesocarps of M. sapientum contained each alkaloids, polyphenols, flavonoids, and triterpenes. Moreover, steroids were also found in G. max, steroids and saponins in epicarps and saponins in bark of C. nucifera. Meanwhile epicarps from M. sapientum contained only polyphenols, flavonoids and saponins. Antibacterial assays showed that different parts of C. nucifera were more active than other extracts. Their minimal inhibitory concentrations (MICs) varied from 128 to 2048 μg/mL. The bark part presented the highest antibacterial potential inhibiting the growth of 90% of strains with significant activity (100≤MIC≤512 μg/mL) against 50% of them (three E. coli, four E. aerogenes and three K. pneumoniae). It showed bactericidal effects (MBC/MIC≤4) on 45% of the same bacterial species. It was followed by epicarps and leaves parts which exhibited an inhibitory power against 75% and 60% of bacteria with significant activity on 40% and 20% of them respectively. They also showed bactericidal effects on E. coli ATCC8739 for epicarps extract and E. coli ATCC8739 and P. stuartii NEA16 for leaves extract. Extracts from G. max were less active and those from mesocarps and epicarps of M. sapientum did not showed any activity on all studied bacteria. Bark and epicarps extracts of C. nucifera potentiated the activities of all used antibiotics against at least 70% of bacteria while leaves extract exhibited this effect improving the activities of 67% of antibiotics with improvement activity factors (IAF) ranging from 2 to 256 suggesting that they contain bioactive compounds which could be considered as efflux pumps inhibitors. Extracts from G. max, epicarps and mesocarps of M. sapientum enhanced the inhibitory potential of 56%, 34% and 23% of antibiotics respectively against at least 70% of studied bacteria. These increases of activities also characterize synergistic effects between antibiotics and bioactive compounds of plants.Conclusion: The findings of this work suggest that infections by resistant bacteria can be treated using different parts of C. nucifera as an alternative to commonly used antibiotics. Keywords: Edible plants; antibiotics; infectious diseases; MDR bacteria; efflux pump

Cytotoxicity, acute and sub-chronic toxicities of the leaves of Bauhinia thonningii (Schumach.) Milne-Redh. (Caesalpiniaceae)

Abstract Background Bauhinia thonningii is a plant traditionally used against many human diseases such as gastric ulcers, fever, inflammations, coughs, dysentery, diarrhea, and malaria. In the present investigation, the cytotoxicity of methanol extract of Bauhinia thonningii leaves (BTL), fractions and the isolated phytoconstituents was determined in a panel of 9 human cancer cell lines including drug sensitive and multidrug-resistant (MDR) phenotypes. The acute and sub-chronic oral toxicity of BTL was investigated as well. Methods Compounds were isolated using chromatographic techniques while their chemical structures were determined using spectroscopic methods. The resazurin reduction assay (RRA) was used to evaluate the cytotoxicity of samples, propidium iodide (PI) for apoptosis, 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazolylcarbocyanine iodide (JC-1) staining for mitochondrial membrane potential (MMP) analysis, 2´,7´-dichlorodihydrofluoresceine diacetate (H2DCFH-DA) staining for the quantification of reactive oxygen species (ROS), whereas Caspase Glo assays were combined by means of flow cytometry. Furthermore, the toxicological investigations were performed as recommended by the Organization for Economic Cooperation and Development (OECD). Results The botanicals as well as 6-C-methylquercetin-3,7-dimethyl ether (2), quercetin-3-O-L-rhamnopyranoside (5), quercetin-3-O-β-glucopyranoside (6), 6,8-C-dimethylkaempferol 3,7-dimethyl ether (7), and 6,8-C-dimethylkaempferol-3-methyl ether (8) had promising cytotoxic effects in the 9 tested cancer cell lines. The IC50 values below 20 µg/mL (botanicals) or 10 µM (compounds) on at least 1/9 tested cancer cell lines were considered. The best cytotoxic effects with IC50 values below 5 µM were achieved with compounds 7 against CEM/ADR5000 leukemia cells (2.86 µM) and MDA-MB-231-pcDNA breast adenocarcinoma cells (1.93 µM) as well as 8 against CCRF-CEM leukemia cells (3.03 µM), CEM/ADR5000 cells (2.42 µM), MDA-MB-231-pcDNA (2.34 µM), and HCT116 p53 −/− cells (3.41 µM). BTL and compound 8 induced apoptotic cell death in CCRF-CEM cells through caspase activation, alteration of MMP, and increased ROS production. BTL did not cause any adverse effects in rats after a single administration at 5000 mg/kg or a repeated dose of 250 mg/kg body weight (b. w.). Conclusion Bauhinia thonningii and its constituents are sources of cytotoxic drugs that deserve more in-depth studies to develop novel antiproliferative phytomedicine to fight cancer including resistant phenotypes

Unprecedented new nonadecyl <i>para</i>-hydroperoxycinnamate isolated from <i>Erythrina excelsa</i> and its cytotoxic activity

<div><p>A new unprecedented cinnamate derivative (<b>1</b>) was obtained from <i>Erythrina excelsa</i> (Leguminosae) and identified as nonadecyl <i>para</i>-hydroperoxycinnamate. This compound was isolated together with three known compounds, namely lupeol (<b>2</b>), mixture of sitosterol and stigmasterol (<b>3</b>), and isoneorautenol (<b>4</b>). Their structures were established on the basis of NMR and mass spectroscopic data in conjunction with those reported in the literature. Compound <b>1</b> was evaluated for its capability of inhibiting cancer cell lines and growth of a panel of microbial strains. It turned out that <b>1</b> is moderately to significantly cytotoxic against six cancer cell lines and shows weak to no antimicrobial activity.</p></div

Cytotoxicity of the methanol extracts and compounds of Brucea antidysenterica (Simaroubaceae) towards multifactorial drug-resistant human cancer cell lines

Youmbi LM, Makong YSD, Mbaveng AT, et al. Cytotoxicity of the methanol extracts and compounds of Brucea antidysenterica (Simaroubaceae) towards multifactorial drug-resistant human cancer cell lines. BMC Complementary Medicine and Therapies. 2023;23(1): 48.BACKGROUND: Cancer remains a global health concern and constitutes an important barrier to increasing life expectancy. Malignant cells rapidly develop drug resistance leading to many clinical therapeutic failures. The importance of medicinal plants as an alternative to classical drug discovery to fight cancer is well known. Brucea antidysenterica is an African medicinal plant traditionally used to treat cancer, dysentery, malaria, diarrhea, stomach aches, helminthic infections, fever, and asthma. The present work was designed to identify the cytotoxic constituents of Brucea antidysenterica on a broad range of cancer cell lines and to demonstrate the mode of induction of apoptosis of the most active samples.; METHODS: Seven phytochemicals were isolated from the leaves (BAL) and stem (BAS) extract of Brucea antidysenterica by column chromatography and structurally elucidated using spectroscopic techniques. The antiproliferative effects of the crude extracts and compounds against 9 human cancer cell lines were evaluated by the resazurin reduction assay (RRA). The activity in cell lines was assessed by the Caspase-Glo assay. The cell cycle distribution, apoptosis via propidium iodide (PI) staining, mitochondrial membrane potential (MMP) through 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolylcarbocyanine iodide (JC-1) staining, and the reactive oxygen species (ROS) via 2,7-dichlorodihydrofluoresceine diacetate (H2DCFH-DA) staining, were investigated by flow cytometry.; RESULTS: Phytochemical studies of the botanicals (BAL and BAS) led to the isolation of seven compounds. BAL and its constituents 3, (3-(3-Methyl-1-oxo-2-butenyl))1H indole (1) and hydnocarpin (2), as well as the reference compound, doxorubicin, had antiproliferative activity against 9 cancer cell lines. The IC50 values varied from 17.42g/mL (against CCRF-CEM leukemia cells) to 38.70g/mL (against HCT116 p53-/- colon adenocarcinoma cells) for BAL, from 19.11M (against CCRF-CEM cells) to 47.50M (against MDA-MB-231-BCRP adenocarcinoma cells) for compound 1, and from 4.07M (against MDA-MB-231-pcDNA cells) to 11.44M (against HCT116 p53+/+ cells) for compound 2. Interestingly, hypersensitivity of resistant cancer cells to compound 2 was also observed. BAL and hydnocarpin induced apoptosis in CCRF-CEM cells mediated by caspase activation, the alteration of MMP, and increased ROS levels.; CONCLUSION: BAL and its constituents, mostly compound 2, are potential antiproliferative products from Brucea antidysenterica. Other studies will be necessary in the perspective of the discovery of new antiproliferative agents to fight against resistance to anticancer drugs. © 2023. The Author(s)

Additional file 1 of Cytotoxicity, acute and sub-chronic toxicities of the leaves of Bauhinia thonningii (Schumach.) Milne-Redh. (Caesalpiniaceae)

Additional file 1: Figure S1-Figure S24

Ericoside, a new antibacterial biflavonoid from Erica mannii (Ericaceae)

A new dihydroflavonol-flavonol biflavonoid derivative, named ericoside was isolated from the ethanol extract of the whole plant of Erica mannii along with the known flavonoid, taxifolin 3-O-α-l-rhamnopyranoside; and two readily available sterols (sitosterol, sitosterol 3-O-β-d-glucopyranoside). The isolation was performed using chromatographic methods and the structure of purified molecules were elucidated using spectroscopic techniques (e.g. MS, NMR) and by comparison with literature data. The crude ethanol extract, ericoside, and taxifolin 3-O-α-l-rhamnopyranoside were tested against ten Gram-negative bacteria including multidrug resistant clinical isolates using a broth microdilution method. The crude ethanol extract showed no noteworthy activity. Of the purified compounds, ericoside displayed moderate activity against the resistant Escherichia coli AG100 with a MIC of 64 μg/mL