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Background. Continuous efforts from scientists of diverse fields are necessary not only to better understand the mechanism by which multidrug-resistant (MDR) cancer cells occur, but also to boost the discovery of new cytotoxic compounds to fight MDR phenotypes. Objectives. The present review reports on the contribution of African flora in the discovery of potential cytotoxic phytochemicals against MDR cancer cells. Methodology. Scientific databases such as PubMed, ScienceDirect, Scopus, Google Scholar, and Web of Knowledge were used to retrieve publications related to African plants, isolated compounds, and drug resistant cancer cells. The data were analyzed to highlight cytotoxicity and the modes of actions of extracts and compounds of the most prominent African plants. Also, thresholds and cutoff points for the cytotoxicity and modes of action of phytochemicals have been provided. Results. Most published data related to the antiproliferative potential of African medicinal plants were from Cameroon, Egypt, Nigeria, or Madagascar. The cytotoxicity of phenolic compounds isolated in African plants was generally much better documented than that of terpenoids and alkaloids. Conclusion. African flora represents an enormous resource for novel cytotoxic compounds. To unravel the full potential, efforts should be strengthened throughout the continent, to meet the challenge of a successful fight against MDR cancers.

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. [Display omitted] •Active efflux as the main resistance strategy in bacteria.•Phytochemicals as promising alternatives against efflux pumps-mediated MDR.•Herbals-based efflux pump inhibitors screening, the methods.

The pharmacopoeias of most African countries are available and contain an impressive number of medicinal plants used for various therapeutic purposes. Many African scholars have distinguished themselves in the fields of organic chemistry, pharmacology, and pharmacognosy and other areas related to the study of plant medicinal plants. However, until now, there is no global standard book on the nature and specificity of chemicals isolated in African medicinal plants, as well as a book bringing together and discussing the main bioactive metabolites of these plants. This book explores the essence of natural substances from African medicinal plants and their pharmacological potential. In light of possible academic use, this book also scans the bulk of African medicinal plants extract having promising pharmacological activities. The book contains data of biologically active plants of Africa, plant occurring compounds and synthesis pathways of secondary metabolites.This book explores the essence of natural substances from African medicinal plants and their pharmacological potentialThe authors are world reknowned African Scientists.

Global public health is facing a real challenge due to infections caused by multidrug-resistant bacteria. Among these bacteria, Staphylococcus aureus is known to rapidly develops antibiotic resistance. This study aimed to evaluate the antibacterial potential of Harungana madagascariensis fruit extracts and their effects on the antioxidant system of multidrug-resistant Staphylococcus aureus . Moreover, the extracts were evaluated for their antibiotic-resistance modulation effects against some multidrug-resistant Staphylococcus aureus . The antibacterial activity of the extracts and their effect in combination with antibiotics were assessed using the micro-dilution method. The catalase activity was assessed by measuring the height of foam, whereas the lipid peroxidation was carried out through spectrophotometric quantification of malondialdehyde. The phytochemical analysis of extracts was carried out using qualitative and quantitative standard assays. The tested extracts showed antibacterial activities, with minimum inhibitory concentrations ranging from 32 to 2048 μg/mL. The most active extract (hexane extract) has inhibited the catalase activity and induced the lipid peroxidation in S. aureus DO18SA, indicating its ability to interact with the antioxidant system of the bacteria. Moreover, the dichloromethane/methanol extract increased by 2–128-fold the activity of levofloxacin, ampicillin, and cefotaxime against selected multidrug-resistant S. aureus . It also showed synergistic effect with cefotaxime against D051SA. Alkaloids, triterpenes, and phenols were detected in all the extracts, whereas the other phytochemical classes were selectively distributed. The methanol extract had the highest phenolic content (142.20 ± 16.75 mg GAE/g of extract). Overall, the findings of this study suggest that extracts of Harungana madagascariensis fruits could be valuable sources of new agents for treating multidrug-resistant Staphylococcus aureus infections.

Botanicals have shown promise in mitigating antibiotic resistance in bacteria. This study examined the efficacy of methanolic extracts from two food plants (Nephelium lappaceum and Hyphaene thebaica), alone and in combination with antibiotics, against critical class priority bacteria, including multi-drug resistant (MDR) strains and clinical isolates of Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterobacter aerogenes, and Escherichia coli. The herbals underwent testing using a 96-well microplate serial dilution technique before being analyzed for their effects on bacterial cell membrane integrity and H+-ATPase-mediated proton pumping. Phytochemical analysis was carried out using established techniques. The bioactive extracts displayed very good to weak antibacterial activities (128 ≤ MIC ≤ 2048 μg/mL). The bark, leaf, and peel extracts of N. lappaceum were found to be effective against all studied MDR bacteria. N. lappaceum leaf extract exhibited the best activity (128 ≤ MIC ≤ 1024 μg/mL on all studied MDR bacteria). Interestingly, all MBC/MIC ratios calculated were ≤ 4, suggesting bactericidal activities. N. lappaceum leaf extract has shown significant inhibition of bacterial H+-ATPase-mediated proton pumping and changes in the cell membrane integrity, suggesting possible modes of action. N. lappaceum (leaves and peels) and H. thebaica (fruits) extracts demonstrated a notable potential to synergize with tetracycline, vancomycin, imipenem, ciprofloxacin, and cefixime (up to 8-fold reduction of the antibiotic's MIC was recorded). N. lappaceum leaves and peels, and fruits of H. thebaica significantly improved the efficacy of all antibiotics tested against K. pneumoniae ATCC11296 at MIC/2. Similar effects were observed against P. aeruginosa PA01 and E. coli AG100, respectively, with leaves and peels of N. lappaceum. No antagonistic interactions were recorded. Qualitative phytochemical screening revealed the presence of tannins, phenols, and saponins in all test extracts. The findings of this study are promising and suggest that N. lappaceum and H. thebaica can be used either for direct action on bacteria or to revitalize outdated antibiotics that are gradually losing their potency due to resistance.

Multidrug resistance is a major factor causing the failure of cancer chemotherapy. Efflux pumps of the ATP-binding cassette (ABC) transporter family expel a large array of diverse anticancer drugs out of tumor cells thereby rendering them unresponsive to drug treatment. During the past 2 decades, we focused on three ABC transporters, i.e. P-glycoprotein (MDR1/ABCB1), breast cancer resistance protein (BCRP/ABCG2), and ABCB5 with the aim to find natural products with activity against multidrug-resistant cells. We investigated more than 102 cytotoxic medicinal plants and more than 228 isolated cytotoxic phytochemicals with defined chemical structures from 16 countries in Africa, Near East, Asia, and Europe for their activity to kill multidrug-resistant cells. A synopsis of these results is given in this review article. ABCB1-, ABCG2- or ABCB5-expressing cells were moderately or strongly cross-resistant to a considerable portion of plant extracts or phytochemicals, making them less suitable for the treatment of multidrug resistant tumors. While another large portion of compounds inhibited sensitive and multidrug-resistant cells with similar efficacy, a small fraction of medicinal plants and phytochemicals (3–8%) suppressed multidrug-resistant cells with even much better efficacy as their drug-sensitive counterparts. This hypersensitivity phenomenon is termed “collateral sensitivity”. These compounds may be exquisitely suited to kill otherwise resistant and refractory tumors. Molecular modes of action of collateral sensitivity as well as possibilities for further drug development, chemical derivatization of natural lead compounds and rationale phytotherapy are discussed.

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.

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).

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 < 10 μg/mL, diospyric acid ( 7 ) significantly inhibited the growth of Escherichia coli AG102, Enterobacter aerogenes ATCC13048, Klebsiella pneumoniae KP55, Providencia stuartii NEA16 and Staphylococcus aureus MRSA3. 28-hydroxy- β -amyrin ( 8 ) significantly impaired the growth of Enterobacter aerogenes EA27, Klebsiella pneumoniae ATCC11296 and Staphylococcus aureus MRSA6; and oleanolic acid ( 9 ) strongly impaired the growth of Escherichia coli AG 102, Enterobacter aerogenes EA27 and Providencia stuartii PS2636. Diospyric acid ( 7 ) and 28-hydroxy- β -amyrin ( 8 ) induced perturbation of H + -ATPase pump and inhibition of the cellular ATP production. Moreover, at MIC/2 and MIC/4, compounds 7 , 8 , and 9 strongly improved the antibacterial activity of norfloxacin, ciprofloxacin and doxycycline with antibiotic-modulating factors ranging between 2 and 64. Conclusion The overall results of the current work demonstrate that diospyric acid ( 7 ), 28-hydroxy- β -amyrin ( 8 ) and oleanolic acid ( 9 ) are the major bioactive constituents of Donella welwitschia towards Gram-negative bacteria expressing MDR phenotypes.

Summary Introduction Continuous efforts from scientists of diverse fields are necessary not only to better understand the mechanism by which multidrug resistant (MDR) cancer cells occur, but also to boost the discovery of new cytotoxic compounds. This work was designed to assess the cytotoxicity and the mechanism of action of flavonoids abyssinone IV ( 1 ), atalantoflavone ( 3 ) and neocyclomorusin ( 6 ) and isoflavonoids sigmoidin I ( 2 ), sophorapterocarpan A ( 4 ), bidwillon A ( 5 ) and 6α-hydroxyphaseollidin ( 7 ) isolated from Erythrina sigmoidea against nine drug sensitive and multidrug resistant (MDR) cancer cell lines. Methods The resazurin reduction assay was used to evaluate the cytotoxicity of the studied compounds whilst caspase-Glo assay was used to detect the activation of caspases enzymes by 1 , 2 , 4 and 7 . Cell cycle, mitochondrial membrane potential and levels of reactive oxygen species were all analyzed via flow cytometry. Results The pterocarpan isoflavonoid 7 displayed the best antiproliferative activity with the IC 50 values below 10 μM obtained on the nine tested cancer cell lines. The IC 50 values below 50 μM were also recorded with compounds 1 , 2 and 4 against the nine cancer cell lines whilst 3 , 5 and 6 showed selective activities. The IC 50 values varied from 14.43 μM (against MDA-MB-231- pcDNA cells) to 20.65 μM [towards HCT116 ( p53 +/+ ) cells] for compound 1 , from 4.24 μM (towards CCRF-CEM cells) to 30.98 μM (towards MDA-MB-231- BCRP cells) for 2 , from 3.73 μM (towards CCRF-CEM cells) to 14.81 μM (against U87MG.Δ EGFR cells) for 4 , from 3.36 μM (towards CCRF-CEM cells) to 6.44 μM (against HepG2 cells) for 7 , and from 0.20 μM (against CCRF-CEM cells) and 195.12 μM (against CEM/ADR5000 cells) for the positive control drug, doxorubicin. Compared to their corresponding sensitive cell lines, collateral sensitivity was observed with HCT116 ( p53 −/− ) to 1 , 2 , 4 , 5 , and 7 and with U87MG.Δ EGFR to 1 to 6 . Compound 7 induced apoptosis in CCRF-CEM cells mediated by the activation of caspases 3/7, 8 and 9 and breakdown of MMP and increase in ROS production, whereas the apoptotic process induced by 1 , 2 and 4 was mediated by the loss of MMP as well as increase in ROS production. Conclusions Compounds from Erythrina sigmoidea and mostly 6α-hydroxyphaseollidin are potential antiproliferative natural products that deserve more investigations to develop novel anticancer drugs against sensitive and otherwise drug-resistant phenotypes.