Search

Abstract Background Origanum species have been used in various commercial constructions as a remedy against burns and wounds, agriculture, alcoholic drinks, fragrance, and flavoring substances of food products. The essential oil of Origanum onites L. (EOOO) and its component carvacrol (CV) possesses a wide range of biological activities including anti-cancer activity. Purpose The purpose of this study was to investigate the growth inhibitory activity of the essential oil and its major component CV and then hepatotoxicity pathway-related genes in HepG2 cells. Methods The effects of the EOOO and CV on cell growth and mRNA expressions of 84 hepatotoxicity pathway-related genes were investigated in HepG2, using trypan blue exclusion/ bromodeoxyuridine (BrdU) incorporation tests and real-time-polymerase chain reaction (RT-PCR) array, respectively. Results The EOOO and CV inhibited cell growth with IC50 values of 0.08 µg/mL and 45 µg/mL, respectively, after 24 h. Real-time, reverse-transcription-polymerase chain reaction (RT2-PCR) array analysis revealed that expressions of 32 genes out of 84 were changed at least 2-fold or more in the EOOO-treated cells. Among them, expression levels of 17 genes were elevated, while expression levels of 15 genes were diminished. Furthermore, after exposure of cells to 45 µg/mL of CV, the expression of 8 genes was increased while the other 8 genes were decreased. Both the EOOO and carvacrol affected the expression of 48 genes of HepG2 cells which are involved in the hepatotoxicity pathway, indicating their hepatoprotective and possible anti-hepatocarcinogenic effects. Conclusion The present study demonstrates that the essential oil of Origanum onites and carvacrol can be used in various applications such as anticancer or herbal drugs, since its non-hepatotoxicity.

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.

Malarial and bacterial coinfections in low-income countries are a serious cause of morbidity and mortality, necessitating coadministration of antibiotics and antimalarials. This study investigated the relationship between malaria infection and bacterial drug resistance in malaria and nonmalaria patients on consultation at the Dschang Regional Hospital. A follow-up study was carried out from October 2020 to December 2021 on 127 malaria and 174 nonmalaria patients having enteric infections. Clinical and haematological parameters were measured using standard methods. CD4 and CD8 cells were determined using flow cytometry. Enteric bacteria pathogens were isolated from stool, and antimicrobial and antimalarial profiles were determined using agar diffusion and microdilution methods, respectively. Significant reduction of RBCs, WBCs, CD4, CD8, granulocytes, monocytes and platelets was seen in coinfected patients compared to monoinfected participants (p≤0.0491). E. coli was the main pathogenic bacteria isolated from the digestive tract of coinfected patients (40.63%) and monoinfected patients (59.37%). E. coli showed a high level of resistance to AMX (57.69%) and CDA (61.54%) in coinfected patients compared to 55.26% and 41.67%, respectively, in monoinfected patients. Quinine (53[50.00%]; 6[42.86%]) presented a minimal inhibitory concentration (MIC) of 32 μg/mL on the bacteria isolates from coinfected and monoinfected patients, respectively, while Artemether 89 (83.96%), Maloxine 5 (3.94%) and Surquina 250 (39.37%) presented a MIC of 64 μg/mL on bacterial isolates of coinfected and monoinfected patients. E. coli showed high resistance against AKI (45.93%), AMX (43.75%) and ERY (59.37%) in malaria patients who were under antimalarial drugs compared to malaria patients who were not under malaria drugs (29.68%, 34.37% and 32.81%, respectively). This study highlights that antimalarial drugs might certainly have an influence on the acquisition and emergence of bacterial resistance in the case of malaria bacterial coinfection, and therefore, adequate management and planning effective control programmes might certainly go a long way to reduce the rate of morbidity and mortality.

Patients with cancer have weakened immune systems, making them more vulnerable to infections. This study was carried out to determine the bacterial origins of enteric disorders in cancer patients and noncancer patients at the Oncology Department of Laquintinie Hospital in Douala. A cross-sectional study was conducted from October 2021 to March 2023. Stool samples from 307 cancer patients with enteric disorders and 200 noncancer patients with enteric disorders were examined to diagnose the presence of bacteria using various techniques. Among all participants in this study, 62.13% were female and 37.87% were male. The average age of the participants was 46.38 ± 15.81 years, with a minimum age of 10 years and a maximum age of 84 years. The average age of participants was significantly higher (p

Background. Opportunistic infections are the second cause of death among cancer patients. This study aimed at determining the antimicrobial profile and the prevalence of extended-spectrum beta-lactamase (ESBL)-gene carriage of Pseudomonas aeruginosa isolates among cancer patients at the Douala Laquintinie Hospital, Littoral Region of Cameroon. Between October 2021 and March 2023, 507 study participants were recruited among whom 307 (60.55%) were cancer patients, compared to 200 (39.45%) noncancer patients. Fifty-eight P. aeruginosa isolates were isolated from fecal samples of forty-five cancer patients and thirteen noncancer patients using Cetrimide agar. The antimicrobial resistance profile of the isolates was determined using the Kirby–Bauer disk diffusion method. The polymerase chain reaction was used to detect the presence of extended-spectrum beta-lactamase genes among P. aeruginosa isolates. P. aeruginosa showed significant resistance rates in cancer patients compared to noncancer patients to imipenem, cefotaxime, and ceftazidime, piperacillin-tazobactam, ticarcillin-clavulanic acid, and ciprofloxacin. The multidrug resistance (MDR) rate was significantly (p

Abstract 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 17.42 µg/mL (against CCRF-CEM leukemia cells) to 38.70 µg/mL (against HCT116 p53 −/− colon adenocarcinoma cells) for BAL, from 19.11 µM (against CCRF-CEM cells) to 47.50 µM (against MDA-MB-231-BCRP adenocarcinoma cells) for compound 1, and from 4.07 µM (against MDA-MB-231-pcDNA cells) to 11.44 µM (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.

Abstract Background The rise of multidrug-resistant (MDR) bacteria is a real public health problem worldwide and is responsible for the increase in hospital infections. Donella welwitschii is a liana or shrub belonging to the family Sapotaceae and traditionally used to cure coughs. Objective This study was conducted with the objective to validate the medicinal properties of this plant, the aerial part was studied for its phytochemical composition using column and PTLC chromatography and exploring its antibacterial and antibiotic-modifying activity as well as those of its phytochemicals. Methods The structures of the compounds were elucidated from their physical and spectroscopic data in conjunction with literature. The antibacterial activity of the isolated metabolites was performed toward a panel of MDR Gram negative and Gram-positive bacteria. The broth micro-dilution method was used to determine antibacterial activities, efflux pump effect using the efflux pump inhibitor (EPI) (phenylalanine-arginine-ß-naphthylamide (PAβN)), as well as the modulating activity of antibiotics. Monitoring the acidification of the bacterial growth medium was used to study the effects of the samples on the bacterial proton-ATPase pumps and cellular ATP production. Results Eleven compounds were isolated including pentacyclic triterpenes, C-glucosyl benzophenones. With a MIC value

Abstract Background Tetrapleura tetraptera is a medicinal spice traditionally used to treat cancer, diabetes, and several other ailments. This study analyzed the cytotoxicity of the dichloromethane methanol extract of T. tetraptera fruits (TTF) and its constituents. The toxicity profile of the TTF extract was also evaluated in rats. Methods The Cytotoxicity of this extract was evaluated using the resazurin reduction assay (RRA). Acute and sub-chronic toxicity studies were performed according to the protocol described by the Organisation for Economic Cooperation, and Development (OECD). Hematological, serum, and urine biochemical parameters, as well as histological sections of the liver and kidney, were also evaluated based on standard methods. Results The TTF extract, compound 5, and the reference drug doxorubicin were active in all 9 tested cancer cell lines. The recorded IC50 ranged from 18.32 μM (against B16-F1 murine melanoma cells) to 36.18 μM (against SKMel-505 BRAF wildtype melanoma cells) for TTF, from 10.02 μM (towards MaMel-80a BRAF-V600E homozygous mutant melanoma cells) to 31.73 μM (against SKMel-28 BRAF-V600E homozygous mutant melanoma cells) for compound 5, and from 0.22 μM (against B16-F1 cells) to 9.39 μM (against SKMel-505 cells) for doxorubicin. The study of acute toxicity test showed that the lethal dose (LD50) of this extract was greater than 5000 mg/kg body weight. In the sub-chronic toxicity studies, variations were observed in some biochemical parameters, especially at higher doses. Conclusion TTF and its most active compound (5) are found to be potential cytotoxic agents, meanwhile, TTF was safe when given a single oral dose of 5000 mg/kg. However, caution is necessary in case of prolonged oral administration due to potential alterations of renal function at high doses (> 1000 mg/kg).

Abstract Background Multidrug-resistant (MDR) bacteria remain a major cause of morbidity and mortality globally. The present study was designed to investigate the in vitro antibacterial activities of crude methanol extract and constituents isolated by Column Chromatography (CC) from Cassia sieberiana bark (CSB) against ten MDR Gram-negative bacteria, as well as the mechanisms of action of the most active sample. Methods The antibacterial activity of the tested samples (extract, the fractions and their compounds isolated by CC and the structures obtained by exploiting 1H and 13C Nuclear magnetic resonance (NMR) spectra) in the presence and absence of an efflux pumps inhibitor, phenylalanine-arginine β-naphthylamide (PAβN), was evaluated using the micro-dilution method. The effects of the most active sample were evaluated on the cell growth kinetic and on the bacterial H+-ATPase proton pumps. Results Phytochemical composition of the crude extract showed a rather selective distribution of secondary metabolites (presence of polyphenols, tannins, steroids, triterpenes, flavonoids, alkaloids, saponins and absence of anthocyanins, anthraquinones). The tested samples displayed different antibacterial activities with minimal inhibitory concentrations (MICs) ranging from 64 to 512 μg/mL. Crude extract (CS) and fraction CSc showed the highest inhibitory spectra, both inhibiting all of the studied bacteria except Enterobacter aerogenes EA27 strain. Fraction CSc exerted bactericidal effects on most bacteria meanwhile, crude extract (CS) and sub-fraction CSc2 exerted bacteriostatic effects. Compounds 1 (spectaline) and 2 (iso-6-cassine) inhibited the growth of 70% (Escherichia coli ATCC8739 and AG102, Klebsiella pneumoniae ATCC11296, Enterobacter aerogenes ATCC13048 and EA27, Providencia stuartii ATCC29916, Pseudomonas aeruginosa PA01) and 60% (Escherichia coli ATCC8739, Klebsiella pneumoniae ATCC11296 and KP55, Providencia stuartii ATCC29916, Pseudomonas aeruginosa PA01 and PA124) of bacteria respectively with MICs ranging from 128 to 512 μg/mL. In the presence of PAβN, the activities of crude extract CS, fraction CAc and sub-fraction CSc2 strongly increased on most bacteria strains as their MICs significantly decreased. Sub-fraction CSc2 inhibited the H+-ATPase proton pumps and altered growth kinetic of Escherichia coli ATCC8739. Conclusion The overall results justify the traditional use of C. sieberiana for the treatment of bacterial infections.

Objectives This study aimed to investigate the immunological and bacterial profiles in pregnant women of Bafang-Cameroon. Methods Stool and midstream urine were cultured using specific culture media. The disk diffusion method was used for the antimicrobial susceptibility test. T-cell lymphocyte counts (CD3, CD4 and CD8), white blood cell counts, sensitive C-reactive protein, and interleukin-6, were measured by flow cytometry, optical detection, and the enzyme-linked immunosorbent assay solid phase direct sandwich method. Results Out of 700 participants, 71.43% were pregnant, and 28.57% were non-pregnant women. The mean age was 29.40 ± 8.27 and 27.41 ± 6.55 years in non-pregnant and pregnant women, respectively. CD4 T-cells were not significantly lower in pregnant women compared with non-pregnant women. There were 43.65% and 56.35% bacteria isolates obtained from urine and stool samples, respectively. Bacteria were mostly isolated in patients with a CD4 T-cell count between 461 and 806 cells/μL. Isolates of Klebsiella pneumoniae and Enterobacter aerogenes showed 100% resistance in non-pregnant women, however all isolated bacteria were shown to be multidrug resistant in pregnant women. Salmonella sp. (24.3%) and Escherichia coli (21.51%) showed an increase in multidrug resistant phenotypes in pregnant women. Conclusion This study demonstrated that routine bacteriological analysis during pregnancy is necessary for their follow-up care.

Abstract Background The cytotoxicity of the root’s methanol extract of Imperata cylindrica (ICR). was previously reported in a panel of human cancer cell lines, including multi-drug resistant phenotypes. The aim of this study was to assess the acute and sub-chronic oral toxicity of methanol root extract of Imperata cylindrica. Methods The acute toxicity was carried out according to the experimental protocol of OECD. The plant extract was administered orally to female rats at a single dose of 5000 mg/kg for 14 days and the animals were observed for any behavioral changes or mortality. For sub-chronic toxicity study, ICR was orally administered daily to male and female rats at different doses (250, 500 and 1000 mg/kg per b.w.) for 30 days. During these treatment days the animals were observed for any appearance of toxicity symptoms; following the treatment period, animals were sacrificed for hematological, biochemical and histopathology analysis. Results From the results of the acute oral toxicity assay, ICR was found to be non-toxic at the dose of 5000 mg/kg b.w. During the period of sub-chronic toxicity test, observation of signs, behavior and health status of the animals showed no abnormality in the groups of animals treated with ICR as compared to the controls. Significant variation of the relative body weights of heart and kidney were observed at dose a 1000 mg/kg b.w. Significant decrease of aspartate aminotransferase, creatinine level, low density lipoprotein concentration, triglyceride and total cholesterol were observed. In males, we noticed a significant decrease of the level of granulocytes with an increase of lymphocytes and mean corpuscular hemoglobin concentration levels. Histological examinations performed on kidney and liver showed a normal kidney architecture and liver also presented a normal hepatic architecture with slight degeneration at a dose 1000 mg/kg b.w. Conclusion ICR is safe for acute oral administration; however, for long-term oral administration, safety measures should be taken. Thus, oral sub-chronic exposure of ICR at lower doses are recommended while higher doses around 1000 mg/kg b.w. should be discouraged.

The upsurge of multiple drug resistance (MDR) bacteria substantially diminishes the effectiveness of antibiotic arsenal and therefore intensifies the rate of therapeutic failure. The major factor in MDR is efflux pump-mediated resistance. A unique pump can make bacteria withstand a wide range of structurally diverse compounds. Therefore, their inhibition is a promising route to eliminate resistance phenomenon in bacteria. Phytochemicals are excellent alternatives as resistance-modifying agents. They can directly kill bacteria or interact with the crucial events of pathogenicity, thereby decreasing the ability of bacteria to develop resistance. Numerous botanicals display noteworthy efflux pumps inhibitory activities. Edible plants are of growing interest. Likewise, some plant families would be excellent sources of efflux pump inhibitors (EPIs) including Apocynaceae, Berberidaceae, Convolvulaceae, Cucurbitaceae, Fabaceae, Lamiaceae, and Zingiberaceae. Easily applicable methods for screening plant-derived EPIs include checkerboard synergy test, berberine uptake assay and ethidium bromide test. In silico high-throughput virtual detection can be evaluated as a criterion of excluding compounds with efflux substrate-like characteristics, thereby improving the selection process and extending the identification of EPIs. To ascertain the efflux activity inhibition, real-time PCR and quantitative mass spectrometry can be applied. This review emphasizes on efflux pumps and their roles in transmitting bacterial resistance and an update plant-derived EPIs and strategies for identification.

Objectives This study aimed to identify virulent and antimicrobial resistant genes in fecal E. coli in Mbouda, Cameroon. Methods A total of 599 fecal samples were collected from patients with enteric infections who were ≥ 20 years old. E. coli was isolated on the MacConkey agar and virulent genes were detected by multiplex/simplex PCR. Isolates in which ≥ 1 virulent gene was detected were subjected to antibiotic susceptibility testing. The resulting resistant isolates were subjected to PCR, followed by sequencing for resistant genes detection. Results There were 119 enterovirulent E. coli identified, amongst which 47.05% were atypical enteropathogenic E. coli (EPEC), 36.97% enterotoxigenic E. coli, 10.08% Shiga toxin producing E. coli (STEC) and 5.88% were enteroinvasive E. coli (EIEC). The occurrence of the eae gene (47.06%) was higher compared with CVD432 (33.61%), aaic (13.45%), stx2 (10.08%) and stx1 (0.84%). High resistance rates were noted for ampicillin (94.64% EPEC, 91.67% STEC, 59.09% EAEC, and 57.14% EIEC) and sulfamethoxazole-trimethoprim (100% EPEC and 83.33% STEC, 81.82% EAEC and 71.43% EIEC). sul2 (71.43%), tetB (64.71%), tetA (59.94%) and blaTEM (52.10%) were detected. A double mutation (S83L; D87N) was seen in gyrA and a single mutation (S80I) was observed in parC. Conclusion These findings suggested that measures should be taken to reduce the harm of E. coli to public health.

Background: Cancer constitutes a major hurdle worldwide and its treatment mainly relies on chemotherapy. Objectives: The present study was designed to evaluate the cytotoxicity of eleven naturally occurring compounds including six phenolics amongst them were 4 chalcones and 2 flavanones as well as 5 terpenoids (3 clerodane and 2 trachylobane diterpenoids) against 6 human carcinoma cell lines and normal CRL2120 fibroblasts. Materials and methods: The neutral red uptake (NR) assay was used to evaluate the cytotoxicity of the compounds, whilst caspase-Glo assay was used to detect caspase activation. Cell cycle and mitochondrial membrane potential (MMP) were all analyzed via flow cytometry meanwhile levels of reactive oxygen species (ROS) was measured by spectrophotometry. Results: Chalcones: 2′,4′-dihydroxy-6′-methoxychalcone (1); 4′,6′-dihydroxy-2′,5′-dimethoxychalcone (2); 2′,4′,6′-trihydroxy-5′-methoxychalcone (3); 2′,6′-diacetate-4′-methoxychalcone (4), trachylobane diterpenoids: 2,6,19-trachylobanetriol; (ent-2α,6α)-form (10) and 2,18,19-trachylobanetriol; (ent-2α)-form (11) as well as doxorubicin displayed IC50 values below 110 μM in the six tested cancer cell lines. The IC50 values of the most active compounds were between 6.30 μM and 46.23 μM for compound 1 respectively towards breast adenocarcinoma MCF-7 cells and small lung cancer A549 cells and between 0.07 μM and 1.01 μM for doxorubicin respectively against SPC212 cells and A549 cells. Compounds 1 induced apoptosis in MCF-7 cells mediated by increasing ROS production and MMP loss. Conclusion: Chalcones 1–3 are potential cytotoxic phytochemicals that deserve more investigations to develop novel anticancer drugs against human carcinoma. Keywords: Carcinoma, Cytotoxicity, Diterpenoids, Mode of action, Phenolics

Abstract Background Albizia adianthifolia (Schum.) is medicinally used in Cameroon to manage bronchitis and skin diseases. Our previous study documented the antibacterial potential of its roots’ methanol extract. In this study, methanol roots extract was subjected to chromatography techniques and fractions (AARa and AARb), sub-fractions (AARa1–4, AARb1–2 and AARb11–14) together with isolated phytochemicals were assessed for their antimicrobial as well as their antibiotic-potentiating effects towards Gram-negative multidrug resistant (MDR) bacteria. Methods The antibacterial activities of the samples (determination of Minimal Inhibitory « MIC » and Minimal Bactericidal Concentration « MBC ») were determined by the modified rapid p-iodonitrotetrazolium chloride (INT) colorimetric assay, as well as those of antibiotics in association with the compounds. Column chromatography was applied to isolate phytochemicals from roots extract and their chemical structures were determined using spectroscopic techniques. Results The phytochemicals isolated were stearic acid (1), a mixture (1:1) of stigmasterol and β-sitosterol (2 + 3), β-sitosterol 3-O-β-D-glucopyranoside (4), palmatin (5), homomangiferin (6) and mangiferin (7). Fraction AARa exhibited selective inhibitory effects whilst all tested bacteria were inhibited by AARb in MIC ranges of 8 to 1024 μg/mL. Sub-fractions AARb1–2 had MIC values between 8 μg/mL and 1024 μg/mL on all tested bacteria. Phytochemicals 4, 2 + 3 and 7 inhibited the growth of 54.54% (6/11), 45.45% (5/11) and 27.27% (3/11) tested bacterial strains, respectively. When tested with an efflux pumps inhibitor (Phenylalanine-Arginine-β-Naphthylamide or PAβN), the inhibitory effects of compounds 2 + 3 and 4 increased towards all the tested bacteria. In association with erythromycin (ERY), streptomycin (STR) and tetracycline (TET), compounds 2 + 3 and 4 had the most significant synergistic activity on the seven selected bacteria. Conclusion The present study provides information on the possible use of Albizia adianthifolia and its constituents in the control of Gram-negative infections including MDR phenotypes.

An effective response that combines prevention and treatment is still the most anticipated solution to the increasing incidence of antimicrobial resistance (AMR). As the phenomenon continues to evolve, AMR is driving an escalation of hard-to-treat infections and mortality rates. Over the years, bacteria have devised a variety of survival tactics to outwit the antibiotic’s effects, yet given their great adaptability, unexpected mechanisms are still to be discovered. Over-expression of efflux pumps (EPs) constitutes the leading strategy of bacterial resistance, and it is also a primary driver in the establishment of multidrug resistance (MDR). Extensive efforts are being made to develop antibiotic resistance breakers (ARBs) with the ultimate goal of re-sensitizing bacteria to medications to which they have become unresponsive. EP inhibitors (EPIs) appear to be the principal group of ARBs used to impair the efflux system machinery. Due to the high toxicity of synthetic EPIs, there is a growing interest in natural, safe, and innocuous ones, whereby plant extracts emerge to be excellent candidates. Besides EPIs, further alternatives are being explored including the development of nanoparticle carriers, biologics, and phage therapy, among others. What roles do EPs play in the occurrence of MDR? What weapons do we have to thwart EP-mediated resistance? What are the obstacles to their development? These are some of the core questions addressed in the present review.

Bacterial multidrug resistance causes many therapeutic failures, making it more difficult to fight against bacterial diseases. This study aimed to investigate the antibacterial activity of extract, fractions, and phytochemicals from Plectranthus glandulosus (Lamiaceae) against multidrug-resistant (MDR) Gram-negative phenotypes expressing efflux pumps. The crude extract after extraction was subjected to column chromatography, and the structures of the isolated compounds were determined using spectrometric and spectroscopic techniques. Antibacterial assays of samples alone and in the presence of an efflux pump inhibitor (phenylalanine-arginine β-naphthylamide, PAβN) were carried out using the broth microdilution method. The phytochemical study of P. glandulosus plant extract afforded seven major fractions (A–G) which lead to the isolation of seventeen known compounds. The ethanol extract of P. glandulosus was not active at up to 1024 μg/mL, whereas its fractions showed MICs varying from 32 to 512 μg/mL on the studied bacteria. Fraction C of P. glandulosus showed the lowest MIC (32 μg/mL) on E. coli ATCC8739 strain. Fraction D presented the highest activity spectrum by inhibiting the growth of 90% (9/10) of the studied bacteria. The presence of PAβN has improved the activity of extract and all fractions. Overall, the tested phytochemicals showed low activity against the studied bacteria. The overall results obtained in this study show that some fractions from P. glandulosus, mainly fractions C and D, should be investigated more for their possible use to fight against MDR bacteria.

Microbial infections are leading causes of death and morbidity all over the world due to the development of the resistance to antibiotics by certain microorganisms. In this study, the chemical exploration of the ethanol (EtOH) extract of the aerial part of Dracaena stedneuri (Dracaenaceae) led to the isolation of one previously unreported chalcone derivative, i.e., 2′,4′-dihydroxy-2,3′-dimethoxychalcone (1), together with 12 known compounds: 8-(C)-methylquercetagetin-3,6,3′-trimethyl ether (2), methylgalangine (3), quercetin (4), kaempferol (5), 6,8-dimethylchrysin (6), ombuine-3-O-rutinoside (4ʹ,7-dimethylquercetin-3-O-α-L-rhamnopyranosyl-(1 → 6) -β-D-glucopyranoside) (7), alliospiroside A (8), β-sitosterol 3-O-glucopyranoside (9), ishigoside (10), betulinic acid (11), oleanolic acid (12), and lupeol (13). The structures were determined by spectroscopic and spectrometric analysis including 1- and 2-Dimensional Nuclear Magnetic Resonance (1D- and 2D-NMR), High-Resolution Electrospray Ionization Mass Spectrometry (HRESIMS), and comparison with literature data. The isolated secondary metabolites and crude extract displayed antibacterial activity against some multidrug-resistant strains with minimal inhibitory concentration (MIC) values ranging from 32 to 256 μg/mL. The antibacterial activity of compound 13 against Enterobacter aerogenes ATCC13048 (MIC value: 32 μg/mL) was higher than that of chloramphenicol used as the reference drug (MIC = 64 μg/mL).

The efficiency of cancer chemotherapy is seriously hampered by the development of resistance of neoplastic cells to cytotoxic agents. In the present investigation, the cytotoxicity of the dichloromethane-methanol (1:1) extract of Acacia sieberiana (ASL), fractions (ASLa-c) from the leaves and isolated compounds: chrysoeriol-7-O-rutinoside (1), luteolin-7-O-rutinoside (2), chrysoeriol-7-O-β-D-glucopyranoside (3), Apigenin-7-O-β-D-glucopyranoside (4), luteolin-3′,4′-dimethoxylether-7-O-β-D-glucoside (5) and luteolin (6) was investigated. The study was extended to the assessment of the mode of induction of apoptosis by ASL. The resazurin reduction assay (RRA) was used for cytotoxicity studies. Assessments of cell cycle distribution, apoptosis, and reactive oxygen species (ROS) were performed by flow cytometry. A caspase-Glo assay was used to evaluate caspase activities. Botanicals ASL, ASLb and ASLc as well as doxorubicin displayed observable IC50 values towards the nine tested cancer cell lines while ASLa and compounds 1–7 had selective activities. The IC50 values ranged from 13.45 μg/mL (in CCRF-CEM leukemia cells) to 33.20 μg/mL (against MDA-MB-231-BCRP breast adenocarcinoma cells) for ASL, from 16.42 μg/mL (in CCRF-CEM cells) to 29.64 μg/mL (against MDA-MB-231-pcDNA cells) for ASLc, and from 22.94 μg/mL (in MDA-MB-231-BCRP cells) to 40.19 μg/mL (against HCT116 (p53−/−) colon adenocarcinoma cells) for ASLb (Table 1), and from 0.02 μM (against CCRF-CEM cells) to 122.96 μM (against CEM/ADR5000 cells) for doxorubicin. ASL induced apoptosis in CCRF-CEM cells, mediated by ROS production. Acacia sieberiana is a good cytotoxic plant and should be further explored to develop an anticancer phytomedicine to combat both sensitive and drug resistant phenotypes.

Piper capense Linn is a plant used in Cameroon to treat cancer and several other diseases such as urinary tract disorder, fever, stomach-ache and to improve appetite. The methanol extract of Piper capense has been reported for its antiproliferative activity towards several human cancer cell lines. The aim of this work was to evaluate the acute and subchronic oral toxicities of a methanol extract from P. capense fruits on rats. The acute oral toxicity assay was carried out by administration of a single dose of 5000 mg/kg body weight of methanol extract of the Piper capense to five female rats, after which the behavior of the animals and the number of deaths were noted after 48 h. The animals were then kept for observation for 14 days. On the 15th day, the rats were sacrificed and macroscopic observation of the organs was made. Concerning the subchronic toxicity study, the rats composed of males and females received three doses (250, 500 and 1000 mg/kg body weight/day) for a period of 28 days by oral gavage. General animal behavior, food intake, weight gain, organ weights, haematological parameters, serum, and urinary biochemical parameters, and histological sections of liver and kidneys, were evaluated. Methanol extract from the Piper capense fruits did not cause any death in rats that were administered a single dose of 5000 mg/kg body weight of extract and therefore, the letal dose 50 (LD50) of the extract is greater than 5000 mg/kg body weight. Subchronic administration of the methanol extract of Piper capense fruits showed significant variations (P > 0.05) after analysis of certain biochemical parameters: serum urea, urinary urea, alanine aminotransferase (ALAT), aspartate aminotransferase, (ASAT), serum protein; in both male and female rats that received the dose of 1000 mg/kg body weight/day. No major signs of toxicity were observed in the liver and kidneys of animals after analysis of the histological sections performed. Beside, some signs of toxicity were observed, including cell lysis and inflammation on the liver and kidney organs at a dose of 1000 mg/kg body weight/day. Finally, the methanol extract of Piper capense fruits is safe at lower doses, but could cause some damages at doses as high as 1000 mg/kg body weight/day. Consequently, it should be taken with caution when used in therapy.

This study falls within the search for alternative solutions to problems related to diseases associated with oxidative stress. It involved the evaluation of antioxidant activities extracts from thirteen antibacterial Cameroonian food plants, namely, P. nigrum, A. cruentus, L. sativa, S. edule, S. nigrum, V. amygdalina, A. hybridus, V. hymenolepis, L. capensis, M. esculenta, C. melo, T. occidentalis, and T. triangulare. The thirteen plant extracts with a broad spectrum of antibacterial activity all showed total reducing powers ranging between 2.41 and 27.81 AAE (mg ascorbic acid equivalents per gram of dried extract) and total phenol contents between 2.65 and 35.03 GAE (mg of gallic acid equivalents per gram of dried extract) of dry extract. Except for extracts of L. capensis, the other 12 extracts showed flavonoid contents ranging between 0.29 and 5.99 RE (rutin equivalents per gram of dried extract). All 13 plant extracts also showed free radical scavenging activity against DPPH· with IC50 ranging between 1.65 and 310.52 μg/ml, while 12 of these extracts exhibited inhibitory activity against NO· radical (IC50 ranging from 19.77 to 157.72 μg/ml). Statistically insignificant positive correlations (p>0.5) were found between antibacterial activities of these plants and their antioxidant activities. The different results of this study provide scientific evidence for the use of these antibacterial food plants in the control of different conditions associated with oxidative stress.

Abstract Background Despite the remarkable progress in cancer therapy in recent years, this disease still remains a serious public health concern. The use of natural products has been and continues to be one of the most effective ways to fight malignancies. The cytotoxicity of 14 compounds from African medicinal plants was evaluated in four human carcinoma cell lines and normal fibroblasts. The tested samples included: β-spinasterol (1), friedelanone (2), 16β-hydroxylupeol (3), β-amyrin acetate (4), lupeol acetate (5), sequoyitol (6), rhamnitrin (7), europetin 3-O-rhamnoside (8), thonningiol (9), glyasperin F (10), seputhecarpan B (11), seputhecarpan C (12), seputhecarpan D (13) and rheediaxanthone A (14). Methods The neutral red uptake (NR) assay was used to evaluate the cytotoxicity of samples; caspase-Glo assay, flow cytometry for cell cycle analysis and mitochondrial membrane potential (MMP) as well as spectrophotometry to measure levels of reactive oxygen species (ROS) were performed to detect the mode of action of compounds 9 and 13 in MCF-7 breast adenocarcinoma cells. Results Compounds 3, 9–13 displayed cytotoxic effects against the four tested cancer cell lines with IC50 values below 85 μM. Compounds 9 and 13 had IC50 values below 10 μM in 4/4 and 3/4 tested cell lines respectively. The IC50 values varied from 0.36 μM (against MCF7 cells) to 5.65 μM (towards colon carcinoma DLD-1 cells) for 9, from 9.78 μM (against MCF7 cells) to 67.68 μM (against HepG2 cells) for 13 and 0.18 μM (towards HepG2 cells) to 72 μM (towards Caco-2 cells) for the reference drug, doxorubicin. Compounds 9 and 13 induced cell cycle arrest in Go/G1 whilst doxorubicin induced arrest in G2/M. The two molecules (9 and 13) also induced apoptosis in MCF-7 cells through activation of caspases 3/7 and 9 as well as enhanced ROS production. Conclusion Compounds 9 and 13 are good cytotoxic phytochemicals that should be explored more in future to develop a cytotoxic drug to fight human carcinoma.

Abstract Background Nutmeg is the seed kernel inside the fruit of Myristica fragrans Houtt. (Myristicaceae). It possesses various pharmacological activities but is used in Cameroon only for its flavor in making cakes. The present study thus aimed to investigate the in vitro antibacterial activity and antibiotic modifying activities of crude seed kernel methanol extract (MFS), fractions (MFSa-e) as well as 3′,4′,7-trihydroxyflavone from Myristica fragrans against a panel of multi-drug resistant (MDR) Gram-negative bacteria. Methods The modified rapid p-iodonitrotetrazolium chloride (INT) colorimetric assay was used to determine the Minimal Inhibitory Concentration (MIC) and Minimal Bactericidal Concentration (MBC) on the tested bacteria, as well as those of antibiotics in association with the extract and/or isolated compound. Column chromatography was used for the fractionation and purification of the seed kernel extract whilst the chemical structures of compounds were determined using spectroscopic techniques. Results Phytochemical investigations lead to the isolation of 3′,4′,7-trihydroxyflavone from the fraction MFSb. The crude extract showed antibacterial activity with MICs ranging from 32 to 1024 μg/mL on the majority of the 29 tested Gram-negative bacterial strains. Fraction MFSb inhibited the growth of 100% (29/29) of the tested bacterial strains, as well as the compound 3′,4′,7-trihydroxyflavone (12/12) with a MIC values ranging from 32 to 1024 μg/mL, and 4 to 128 μg/mL respectively. The lowest MIC value (4 μg/mL) was recorded with 3′,4′,7-trihydroxyflavone against Providencia stuartii ATCC299645 as well as the best MBC value (16 μg/mL) against the same strain. In the presence of Phenylalanine-Arginine-β-Naphthylamide (PAßN), an efflux pumps inhibitor, the activity of the extract increased on 73.33% (11/15) meanwhile that of 3′,4′,7-trihydroxyflavone increased on 100% tested bacteria. The compound 3′,4′,7-trihydroxyflavone potentiated the activity of antibiotics in the majority of the tested bacterial strains. Conclusion The results of the present work provide additional information on the use of nutmeg and it major antibacterial component, 3′,4′,7-trihydroxyflavone, as a potential drug in the treatment of bacterial infections including multidrug resistant phenotypes.

The local botanical Imperata cylindrica in Cameroon was investigated for its antibacterial potency. The methanol extract afforded a total of seven compounds, including five hitherto unreported compounds comprising three flavonoids (1–3) and two C-15 isoprenoid analogues (4 and 5) together with known derivatives (6 and 7). The novelty of the flavonoids was related to the presence of both methyl and prenyl groups. The potential origin of the methyl in the flavonoids is discussed, as well as the chemophenetic significance of our findings. Isolation was performed over repeated silica gel and Sephadex LH-20 column chromatography and the structures were elucidated by (NMR and MS). The crude methanol extract and isolated compounds showed considerable antibacterial potency against a panel of multi-drug resistant (MDR) bacterial strains. The best MIC values were obtained with compound (2) against S. aureus ATCC 25923 (32 µg/mL) and MRSA1 (16 µg/mL).

Abstract Background Multidrug resistant (MDR) bacteria are responsible for therapeutic failure and there is an urgent need for novels compounds efficient on them. Methods Eleven methanol extracts from seven Cameroonian medicinal plants were tested for their antibacterial activity using broth micro-dilution method against 36 MDR bacterial strains including Escherichia coli, Enterobacter aerogenes, Enterobacter cloacae, Klebsiella pneumoniae, Providencia stuartii, Pseudomonas aeruginosa and Staphylococcus aureus. Results Euphorbia prostrata extract was found active against all the 36 tested bacteria including Gram-negative phenotypes over-expressing efflux pumps such as P. aeruginosa PA124, E. aerogenes CM64 and E. coli AG102. E. prostrata had minimal inhibitory concentrations values between 128 and 256 µg/mL on 55.55% of the studied microorganisms. Other plants extract displayed selective antibacterial activity. Conclusions Results obtained in this study highlight the antibacterial potential of the tested plants and the possible use of E. prostrata to combat bacterial infections including MDR phenotypes.

Abstract Background Cancer still constitutes one of the major health concerns globally, causing serious threats on patients, their families, and the healthcare system. Methods In this study, the cytotoxicity of the methanol extract of Elephantopus mollis whole plant (EMW), Enantia chlorantha bark (ECB), Kalanchoe crenata leaves (KCL), Lophira alata bark (LAB), Millettia macrophylla leaves (MML) and Phragmanthera capitata leaves (PCL) towards five human solid cancer cell lines and normal CRL2120 fibroblasts, was evaluated. Extracts were subjected to qualitative chemical screening of their secondary metabolite contents using standard methods. The cytotoxicity of samples was evaluated using neutral red uptake (NR) assay meanwhile caspase activation was detected by caspase-Glo assay. Flow cytometry was used to analyze the cell cycle distribution and the mitochondrial membrane potential (MMP) whilst spectrophotometry was used to measure the levels of reactive oxygen species (ROS). Results Phytochemical analysis revealed the presence of polyphenols, triterpenes and sterols in all extracts. The IC50 values of the best samples ranged from 3.29 μg/mL (towards DLD-1 colorectal adenocarcinoma cells) to 24.38 μg/mL (against small lung cancer A549 cells) for EMW, from 2.33 μg/mL (mesothelioma SPC212 cells) to 28.96 μg/mL (HepG2 hepatocarcinoma) for KCL, and from 0.04 μg/mL (towards SPC212 cells) to 0.55 μg/mL (towards A549 cells) for doxorubicin. EMW induced apoptosis in MCF-7 cells mediated by MMP loss and increased ROS production whilst KCL induced apoptosis via ROS production. Conclusion This study provides evidences of the cytotoxicity of the tested plant extract and highlights the good activity of Elephantopus mollis and Kalanchoe crenata. They deserve more exploration to develop novel cytotoxic drugs.

Summary: This study investigated the variations in some cells of the immune system, as well as the antibiotic resistance of the bacteria responsible for enteric infections among HIV+ patients compared to HIV− patients in Mbouda AD LUCEM Hospital, Cameroon.A cross-sectional study was performed from September 2014 to February 2015 in 67 human immunodeficiency virus (HIV)-seropositive (HIV+) and 37 HIV-seronegative (HIV−) patients. Blood collected from these patients was used to perform cluster of differentiation 4 (CD4) and cluster of differentiation 8 (CD8) lymphocyte blood counts and a white blood cell count, as well as to measure C-reactive protein (CRP) blood by flow cytometry and perform optical and immuno-turbidimetric detection. Enteric bacteria were isolated from the stool of patients, and their antibiotic susceptibility profiles were determined using agar diffusion methods.The results showed that Escherichia coli was the main pathogenic bacteria in the digestive tracts of HIV+ (85.3%) and HIV− (81.1%) patients, and infections with Klebsiella sp. were also predominant among HIV− patients (29.4%). Resistance of Klebsiella sp. to ceftriaxone (CRO; P = 0.001), gentamicin (GEN; P = 0.005), chloramphenicol (CHL; P = 0.0004), ciprofloxacin (CIP; P = 0.005) and doxycycline (DOX; P

Human immunodeficiency virus (HIV) infection is a serious problem throughout the world and especially in developing countries. This study was conducted to define the bacterial aetiologies of enteric disorders and their association with CD4+ T-lymphocyte cell count and serum hs-CRP in HIV-seropositive patients coming for consultation at the AD-Lucem Banka Hospital. Stool samples from one-hundred HIV-positive patients with enteric disorders and forty HIV negative patients with enteric disorders were examined for the presence of bacteria by different diagnostic techniques. CD4+ T-lymphocyte count and serum hs-CRP of HIV-positive and HIV-negative patients were examined, respectively, by flux cytometry and the ELISA solid-phase direct sandwich method. Among all the participants, 39 (26.35%) were males and 109 (73.65%) were females. HIV-seropositive mean age (43.79 years) was significantly higher compared to HIV-seronegative (27.13 years) patients (p

Plukenetia huayllabambana is an edible plant traditionally used to cure wounds and various infections. The present work assessed, for the first time, the antibacterial efficacy of solvent fractions from P. huayllabambana fruits. The crude methanol extract was obtained applying ultrasound-assisted extraction, followed by partitioning through successive depletion among solvents of increasing polarity to yield fractions (n-hexane, dichloromethane, ethyl acetate, and n-butanol). The minimal inhibitory concentration (MIC) was determined following antibacterial testing, using the broth microdilution technique against a panel of drug-resistant Gram-negative and Gram-positive bacteria. Possible modes of action of the most active fraction were also investigated. Gas chromatography–mass spectrometry (GC–MS) was used to identify phytocompounds that may account for the recorded activities. Methanol, n-hexane (PH-n-Hex), and ethyl acetate extracts inhibited 100% of studied bacteria, with the recorded MIC ranging from 0.125–1 mg/mL. PH-n-Hex appeared as the most active partition, exerting a bacteriostatic effect. PH-n-Hex probably acts by interfering with bacterial biofilm formation, proton pumps, and bacterial cell membrane integrity. The GC–MS analysis of PH-n-Hex led to the identification of 11 potentially bioactive components, including fatty acids, phytosterol, and diterpene alcohol as major ones. P. huayllabambana can be considered as a plant of pharmacological value—a source of potent anti-infective drug entities.

A series of novel substituted 1-O-alkylglycerols (AKGs) containing methoxy (8), gem-difluoro (9), azide (10) and hydroxy (11) group at 12 position in the alkyl chain were synthesized from commercially available ricinoleic acid (12). The structures of these new synthesized AKGs were established by NMR experiments as well as from the HRMS and elementary analysis data. The antimicrobial activities of the studied AKGs 8–11 were evaluated, respectively, and all compounds exhibited antimicrobial activity to different extents alone and also when combined with some commonly used antibiotics (gentamicin, tetracycline, ciprofloxacin and ampicillin). AKG 11 was viewed as a lead compound for this series as it exhibited significantly higher antimicrobial activity than compounds 8–10.

Drug resistance is one of the main reasons of chemotherapy failure. Therefore, overcoming drug resistance is an invaluable approach to identify novel anticancer drugs that have the potential to bypass or overcome resistance to established drugs and to substantially increase life span of cancer patients for effective chemotherapy. Oridonin is a cytotoxic diterpenoid isolated from Rabdosia rubescens with in vivo anticancer activity. In the present study, we evaluated the cytotoxicity of oridonin toward a panel of drug-resistant cancer cells overexpressing ABCB1, ABCG2, or ΔEGFR or with a knockout deletion of TP53. Interestingly, oridonin revealed lower degree of resistance than the control drug, doxorubicin. Molecular docking analyses pointed out that oridonin can interact with Akt/EGFR pathway proteins with comparable binding energies and similar docking poses as the known inhibitors. Molecular dynamics results validated the stable conformation of oridonin docking pose on Akt kinase domain. Western blot experiments clearly revealed dose-dependent downregulation of Akt and STAT3. Pharmacogenomics analyses pointed to a mRNA signature that predicted sensitivity and resistance to oridonin. In conclusion, oridonin bypasses major drug resistance mechanisms and targets Akt pathway and might be effective toward drug refractory tumors. The identification of oridonin-specific gene expressions may be useful for the development of personalized treatment approaches.

Background. In this study, 18 methanol extracts from Cameroonian edible plants were tested for their antibacterial activities against 26 strains of S. aureus; the role of efflux pumps in the resistance of tested bacteria and the antibiotic resistance-modulating activities against selected multidrug-resistant (MDR) phenotypes were also investigated. Methods. Broth microdilution assay was used to evaluate the antibacterial activity, the role of efflux pumps, and the antibiotic resistance-modulating effects of plant extracts. Results. Extracts from Dacryodes edulis seeds (DES) and Dacryodes edulis bark (DEB) were active against all 26 tested bacterial strains, within the minimal inhibitory concentration (MIC) range of 256–1024 µg/mL. MIC values varied from 64 to 1024 µg/mL against 96.2% of the 26 tested bacteria for Phaseolus vulgaris leaves (PVL), 92.3% for Azadirachta indica bark (AIB), Dacryodes edulis leaves (DEL), and Ricinodendron heudelotii leaves (RHL). The lowest MIC value of 64 µg/mL was obtained with the extract from Cucurbita maxima beans (CMB) against MRSA4 strain and from Uapaca guineensis bark (UGB) against MRSA9 strain. Bacterial efflux pump inhibitor (EPI), carbonyl cyanide m-chlorophenyl hydrazone (CCCP), improved the activity of DES and UGB as well as that of extracts from Hibiscus esculentus leaves (HEL) and Uapaca guineensis leaves (UGL) against resistant S. aureus strains. Antibiotic-modulating effects against more than 70% of the S. aureus strains tested were obtained when RHL (at MIC/2) was combined with CIP, ERY, and KAN (88.89%), CHL (88.89%), TET (77.78%), and STR (88.89%). Conclusion. The present study demonstrated that the 13 tested plants had antistaphylococcal effects and that DES, HEL, UGL, and UGB could be used in combination with EPI to combat resistance to Staphylococcus aureus. Also, it demonstrated that some studied extracts and mostly RHL could be used as antibiotic resistance modulators to fight against resistant strains of S. aureus.

This work was designed to investigate the antibacterial activities of methanol extracts from thirteen Cameroonian edible plants and their antibiotic-potentiating effects against Gram-negative multidrug-resistant (MDR) phenotypes. The broth microdilution method was used to evaluate the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of the extracts, as well as their antibiotic-potentiating activities. The phytochemical screening of the extracts was carried out according to the standard methods. The results of phytochemical tests revealed the presence of sterols, polyphenols, and tannins in most of the tested extracts, with the other classes of secondary metabolites being selectively distributed. Tested extracts showed variable antibacterial activities with MIC values ranging from 64 to 1024 μg/mL. However, some extracts were significantly active against certain bacterial strains: seeds extract of Theobroma cacao (64 μg/mL) against Escherichia coli AG100Atet and Klebsiella pneumoniae K24, and the bark extract of Uapaca guineensis against E. coli ATCC 8739. The leaves extract of T. cacao displayed the best MBC values (256 μg/mL) against E. aerogenes EA27. Some tested extracts included extracts from the leaves of T. cacao and P. vulgaris, and the seeds of D. edulis and barks A. indica has selectively improved (2- to 64-fold) the antibacterial activities of some of the tested antibiotics, chloramphenicol (CHL), tetracycline (TET), kanamycin (KAN), streptomycin (STR), and erythromycin (ERY), against more than 70% of tested MDR bacteria. The findings of this work showed that tested plant extracts and particularly those from T. cacao and Phaseolus vulgaris can be used alone or in combination with conventional antibiotics in the treatment of infections involving multiresistant bacteria.

In order to contribute to the fight against infectious diseases, the in vitro antibacterial activity and the antibiotic-potentiating effects of Tristemma hirtum and five other Cameroonian edible plants have been evaluated against Gram-negative multidrug-resistant (MDR) phenotypes. The microdilution method was used to evaluate the bacterial susceptibility of the extracts and their combination to common antibiotics. The phytochemical screening of the extracts was carried out according to standard methods. Phytochemical analysis of the extracts revealed the presence of alkaloids, triterpenes, steroids, and polyphenols, including flavonoids in most of the tested extracts. The entire tested extracts showed moderate (512 μg/mL ≤ MIC ≤ 2048 μg/mL) to weak (MIC > 2048 μg/mL) antibacterial activities against the tested bacteria. Furthermore, extracts of leaf of Tristemma hirtum and pericarps of Raphia hookeri (at their MIC/2 and MIC/4) strongly potentiated the activities of all antibiotics used in the study, especially those of chloramphenicol (CHL), ciprofloxacin (CIP), kanamycin (KAN), and tetracycline (TET) against 70% (7/10) to 100% (10/10) of the tested MDR bacteria, with the modulating factors ranging from 2 to 128. The results of this study suggest that extracts from leaves of Tristemma hirtum and pericarps of Raphia hookeri can be sources of plant-derived products with antibiotic modifying activity.

This review focuses on pyridoacridine-related metabolites as one biologically interesting group of alkaloids identified from marine sources. They are produced by marine sponges, ascidians and tunicates, and they are structurally comprised of four to eight fused rings including heterocycles. Acridine, acridone, dihydroacridine, and quinolone cores are features regularly found in these alkaloid skeletons. The lack of hydrogen atoms next to quaternary carbon atoms for two or three rings makes the chemical shift assignment a difficult task. In this regard, one of the aims of this review is the compilation of previously reported, pyridoacridine 13C NMR data. Observations have been made on the delocalization of electrons and the presence of some functional groups that lead to changes in the chemical shift of some carbon resonances. The lack of mass spectra information for these alkaloids due to the compactness of their structures is further discussed. Moreover, the biosynthetic pathways of some of these metabolites have been shown since they could inspire biomimetic synthesis. The synthesis routes used to prepare members of these marine alkaloids (as well as their analogues), which are synthesized for biological purposes are also discussed. Pyridoacridines were found to have a large spectrum of bioactivity and this review highlights and compares the pharmacophores that are responsible for the observed bioactivity.

Summary: Treatment of infectious diseases with antimicrobials constituted a great achievement in the history of medicine. Unfortunately, the emergence of resistant strains of bacteria to all classes of antimicrobials limited their efficacy. The present study was aimed at evaluating the effect of combinations of antibiotics on multi-drug resistant Gram-negative (MDRGN) bacteria.A liquid micro-broth dilution method was used to evaluate the antibacterial activity of 10 different classes of antimicrobials on 20 bacterial strains belonging to six different species. The antimicrobials were associated with phenylalanine β-naphthylamide (PAβN), an efflux pump inhibitor, and with other antimicrobials at their sub-inhibitory concentrations. The effectiveness of each combination was monitored using the minimal inhibitory concentration (MIC) and the fractional inhibitory concentration (FIC).Most of the antimicrobials tested showed low antibacterial activity with a MIC value of 128 mg/L on a majority of the bacterial strains, justifying their multidrug-resistant (MDR) profile. Synergistic effects were mostly observed (FIC ≤ 0.5) when ampicillin (AMP), cloxacillin (CLX), erythromycin (ERY), chloramphenicol (CHL), kanamycin (KAN) and streptomycin (STR) were combined with tetracycline (TET) at the sub-inhibitory concentration of MIC/5 or MIC/10.The results of the present work suggest that the association of several antimicrobials with TET could improve the fight against MDRGN bacterial species. Keywords: Antimicrobials, Gram-negative, Multi-drug-resistant bacteria, Synergy, Tetracycline

Cancer remains a major health hurdle worldwide and has moved from the third leading cause of death in the year 1990 to second place after cardiovascular disease since 2013. Chemotherapy is one of the most widely used treatment modes; however, its efficiency is limited due to the resistance of cancer cells to cytotoxic agents. The present overview deals with the potential of the flora of Central, Eastern and Western African (CEWA) regions as resource for anticancer drug discovery. It also reviews the molecular targets of phytochemicals of these plants such as ABC transporters, namely P-glycoprotein (P-gp), multi drug-resistance-related proteins (MRPs), breast cancer resistance protein (BCRP, ABCG2) as well as the epidermal growth factor receptor (EGFR/ErbB-1/HER1), human tumor suppressor protein p53, caspases, mitochondria, angiogenesis, and components of MAP kinase signaling pathways. Plants with the ability to preferentially kills resistant cancer cells were also reported. Data compiled in the present document were retrieved from scientific websites such as PubMed, Scopus, Sciencedirect, Web-of-Science, and Scholar Google. In summary, plant extracts from CEWA and isolated compounds thereof exert cytotoxic effects by several modes of action including caspases activation, alteration of mitochondrial membrane potential (MMP), induction of reactive oxygen species (ROS) in cancer cells and inhibition of angiogenesis. Ten strongest cytotoxic plants from CEWA recorded following in vitro screening assays are: Beilschmiedia acuta Kosterm, Echinops giganteus var. lelyi (C. D. Adams) A. Rich., Erythrina sigmoidea Hua (Fabaceae), Imperata cylindrical Beauv. var. koenigii Durand et Schinz, Nauclea pobeguinii (Pobég. ex Pellegr.) Merr. ex E.M.A., Piper capense L.f., Polyscias fulva (Hiern) Harms., Uapaca togoensis Pax., Vepris soyauxii Engl. and Xylopia aethiopica (Dunal) A. Rich. Prominent antiproliferative compounds include: isoquinoline alkaloid isotetrandrine (51), two benzophenones: guttiferone E (26) and isoxanthochymol (30), the isoflavonoid 6α-hydroxyphaseollidin (9), the naphthyl butenone guieranone A (25), two naphthoquinones: 2-acetylfuro-1,4-naphthoquinone (4) and plumbagin (37) and xanthone V1 (46). However, only few research activities in the African continent focus on cytotoxic drug discovery from botanicals. The present review is expected to stimulate further scientific efforts to better valorize the African flora.

New aryl-hydrazinyl-1,3-selenazole and aroyl-hydrazonyl-1,3-selenazoles were synthesized via Hantzsch type condensation reactions of selenosemicarbazides with α-halogenocarbonyl derivatives, under classical versus microwave heating conditions. Excellent yields and shorter reaction times were obtained under irradiation conditions. The structures of the synthesized compounds were assigned based on spectroscopic data (FT-IR, 1H-NMR), MS and elemental analysis. Selenazole derivatives were screened for their anti-proliferative effects against two leukemia cell lines (CCRF-CEM and HL60) and three carcinoma cell lines (MDA-MB231, HCT116 and U87MG).

BACKGROUND: Natural products are well recognized as sources of drugs in several human ailments. In the present work, we carried out a preliminary screening of six natural compounds, xanthone V(1) (1); 2-acetylfuro-1,4-naphthoquinone (2); physcion (3); bisvismiaquinone (4); vismiaquinone (5); 1,8-dihydroxy-3-geranyloxy-6-methylanthraquinone (6) against MiaPaCa-2 pancreatic and CCRF-CEM leukemia cells and their multidrug-resistant subline, CEM/ADR5000. Compounds 1 and 2 were then tested in several other cancer cells and their possible mode of action were investigated. METHODOLOGY/FINDINGS: The tested compounds were previously isolated from the Cameroonian medicinal plants Vismia laurentii (1, 3, 4, 5 and 6) and Newbouldia laevis (2). The preliminary cytotoxicity results allowed the selection of xanthone V(1) and 2-acetylfuro-1,4-naphthoquinone, which were then tested on a panel of cancer cell lines. The study was also extended to the analysis of cell cycle distribution, apoptosis induction, caspase 3/7 activation and the anti-angiogenic properties of xanthone V(1) and 2-acetylfuro-1,4-naphthoquinone. IC(50) values around or below 4 µg/ml were obtained on 64.29% and 78.57% of the tested cancer cell lines for xanthone V(1) and 2-acetylfuro-1,4-naphthoquinone, respectively. The most sensitive cell lines (IC(50)

Many developing countries including Cameroon have mortality patterns that reflect high levels of infectious diseases and the risk of death during pregnancy and childbirth, in addition to cancers, cardiovascular diseases and chronic respiratory diseases that account for most deaths in the developed world. Several medicinal plants are used traditionally for their treatment. In this review, plants used in Cameroonian traditional medicine with evidence for the activities of their crude extracts and/or derived products have been discussed. A considerable number of plant extracts and isolated compounds possess significant antimicrobial, antiparasitic including anti-malarial, anti-proliferative, anti-inflammatory, anti-diabetes, and antioxidant effects. Most of the biologically active compounds belong to terpenoids, phenolics and alkaloids. Terpenoids from Cameroonian plants showed best activities as anti-parasitic, but rather poor antimicrobial effects. The best antimicrobial, anti-proliferative and antioxidant compounds were phenolics. In conclusion, many medicinal plants traditionally used in Cameroon to treat various ailments displayed good activities in vitro. This explains the endeavor of Cameroonian research institutes in drug discovery from indigenous medicinal plants. However, much work is still to be done to standardize methodologies and to study the mechanisms of action of isolated natural products.