Invasive melanoma accounts for only 1% of skin cancer diagnosed but causes most fatalities. It is the most prevalent malignancy diagnosed in the United States. Scientific databases like Pubmed, ScienceDirect, Scopus, and Google Scholar were used to retrieve information on the cytotoxic activity of botanicals and phytochemicals from the flora of Africa toward drug-sensitive and multidrug-resistant (MDR) melanoma cancer cells. This information was further compiled. As a result, botanicals from Piper capense and Callicarpa longissimi as well as 8,8-bis-(dihydroconiferyl)-diferulate (1), licarin A (2), and soyauxinium chloride (3) were the more suitable samples that could be helpful to combat the multidrug resistance of melanoma cell lines. Extensive preclinical and clinical studies on these natural products are required, to develop novel anti-melanoma drugs.

Abstract Background: Pseudomonas aeruginosa is a critical-class priority pathogen showing high resistance to almost all classes of conventional antibiotics. As a result, discovering new drugs capable of combating Pseudomonas infections becomes critical. The current study looked at the antibacterial and antibiotic-resistance reversal properties of the leaf (PGL) and bark (PGB) methanol extracts of Psidium guajava (Myrtaceae), a popular food plant, towards multidrug-resistant (MDR) P. aeruginosa over-expressing active efflux. Methods: The activities were assessed using a 96-well plate microdilution technique, with iodonitrotetrazolium chloride (INT) to detect living bacteria. The action of herbals was further carried out on Pseudomonas kinetic growth, cell membrane, and H+-ATPase mediated proton pumps, using standards. Results: PGL and PGB produced inhibitory effects on all the fourteen MDR strains and clinical isolates of P. aeruginosa, with the minimum inhibitory concentrations (MIC) recorded ranging from 64 to 2048 μg/mL. PGB was shown to be more effective, having MICs ≤ 512 μg/mL on 100% of the MDR pathogens tested. It also exhibited the lowest MICs (best activity) of 64 μg/mL against three MDR clinical isolates P124, P57, and P29, with activity higher than that of the reference medication (chloramphenicol). PGL and PGB were shown to have significant antibiotic-resistance reversal action when combined with conventional antibiotics, with PGB enhancing the efficacy of all standard drugs employed. PGB was shown to lengthen the latent phase of kinetic growth, also, it significantly inhibited the H+-ATPase-mediated proton pump and altered cell membrane integrity, at MIC and 2×MIC. Conclusion: The current investigation provides justification for considering P. guajava extracts, alone or in combination with antibiotics, as potential treatments for MDR P. aeruginosa infections. Keywords: Antibiotics; efflux pumps; food plants; multidrug-resistant bacteria; Pseudomonas aeruginosa; Psidium guajava.

The present chapter focused on the antibacterial potency of African medicinal plants and their constituents against drug-sensitive and drug-resistant Gram-positive bacteria. Based on collected data, we have established rationale cut-off values for the classification of antibacterial agents towards the Gram-positive bacteria. For botanicals: Outstanding activity: minimal inhibitory concentration (MIC) <= 8 mu g/mL; Excellent activity: 8 < MIC <= 40 mu g/mL; Very good activity: 40 < MIC <= 128 mu g/mL; Good activity: 128 < MIC <= 320 mu g/mL; Average activity: 320 < MIC <= 625 mu g/mL; Weak activity: 625 < MIC <= 1024 mu g/mL; Not active: MIC values > 1024 mu g/mL; (ii) For phytochemicals: Outstanding activity: MIC = 2 mu g/mL; Excellent activity: 2 < MIC <= 4 mu g/mL; Very good activity: 4 < MIC <= 8 mu g/mL; Good activity: 8 < MIC <= 32 mu g/mL; Average activity: 32 < MIC <= 64 mu g/mL; Weak activity: 64 < MIC <= 512 mu g/mL; Not active: MIC > 512 mu g/mL. Based on the above cut-off points, we have identified five African plants displaying outstanding to excellent activities on Gram-positive bacteria. They include Macaranga capensis Benth. (Euphorbiaceae); Macaranga kilimandscharica Pax. and Macaranga conglomerata Brenan (Euphorbiaceae), Salvia africana-lutea L. (Lamiaceae), Erythrophleum lasianthum Corbishley (Caesalpinioideae). Compounds with the corresponding inhibitory effects were plumbagin, emodin, and rapanone. These botanicals and phytochemicals deserve further in-depth studies to develop new medicine to combat Gram-positive bacteria.

Background: Imperata cylindrica is a medicinal spice used in traditional medicine to cure several ailments including cancer, wounds, hypertension, and inflammation. The current study aimed to compile phytochemicals and pharmacological data on Imperata cylindrica. Methods: A bibliographic study was carried out by analyzing conventional textbooks, authentic published studies, and consulting wide-reaching accepted scientific databases. In this review, an attempt is being made to establish an up-to-date chemical profile of I. cylindrica and the classification of its compounds in the main classes of plant secondary metabolites. Moreover, our study highlights the traditional usage of I. cylindrica and the reported investigations regarding the pharmacological properties of this plant. Results: The 43 phytochemicals isolated by various investigators mainly from the roots of I. cylindrica could be classified as bioactive phenolic compounds (coumarins, flavonoids, phenols, lignan glycosides, nor-lignans, phenolic acids, and aurone), few of them also belong to the group of terpenoids (sesquiterpenoids and triterpenoids), steroids and phytosterols. Based on the examined published data, the roots, and leaves of I. cylindrica are outstanding cytotoxic agents against several sensitive and resistant primary cancers through apoptosis induce, G1 cell cycle arrest (roots), and G2/M cell cycle arrest (leaves). Moreover, the root extract prevents metastasis invasion through inhibition of the PI3K/AKT/Snail pathway and the epithelial to mesenchymal transition (EMT) process via modulation of certain key genes. I. cylindrica tackles the growth of sensitive and multidrug-resistant (MDR) pathogenic microorganisms from various species and potentiates the antimicrobial activities of certain families of antibiotics towards MDR bacterial strains. The plant also has significant antihypertensive, anti-hyperglycemic, anti-parasitic, antioxidant activity, and several other pharmacological properties. Various studies characterized the Imperata cylindrica root extract as non-toxic to humans by oral route. Conclusion: From the outcome of this review, I. cylindrica is a potent candidate for drug formulation against primary and metastatic cancers, some drug-resistant microbial infections, and hypertension.

Chemical investigation of the methanol extract from the leaves of H. roeperianum led to the isolation of a new tetraoxygenated xanthone along with eleven known compounds including six xanthones, one polyketide, one flavonoid, one ferulic acid derivative and two pentacyclic triterpenoids. Their structures were established on the basis of 1D- and 2D-NMR, UV, IR, and MS experiments, and by comparison of their spectroscopic data with those of similar compounds reported in the literature. The new xanthone was tested against a panel of eight bacterial strains including six Gram-negative and two Gram-positive bacteria. As results, it exhibited weak antibacterial activity with MIC values ranging from 64 to 128 µg/mL.

Background: The antibiotic resistance of pathogenic bacteria is one of the major health problems worldwide. The development of novel antimicrobial therapies based on natural products that greatly reduce this resistance is urgent. The present study aimed at evaluating the antimicrobial potential of four animal methanol extracts, Gryllus campestris, Testudo hermanni, Cardisoma guanhumi, and Rhinella jimi as well as their synergistic effects with antibiotics against twenty Gram-negative bacteria. Methods: Zoochemical analysis of extracts was performed using qualitative reference methods for the detection of secondary metabolites and the ninhydrin reaction for the detection of protein constituents. The antibacterial activity of animal extracts alone and in combination with antibiotics was carried out using broth microdilution methods. Results: Amino acids, peptides, or proteins were present in all extracts. Alkaloids were detected in extracts of C. guanhumi and R. jimi and were absent in other extracts. Flavonoids, tannins, and steroids were evidenced only in dried and fresh extracts of R. jimi. Polyphenols, anthocyanins, anthraquinones, and saponins were not detected in all extracts. Dried extract from R. jimi was most active. It had antibacterial potential against 85% of the tested bacterial strains with significant activity (100≤MIC≤512 µg/mL) against 35% of bacteria; this included three E. coli (ATCC8739, AG100ATet and MC4100), one E. aerogenes (ATCC13048), one K. pneumoniae (ATCC11296) and two P. aeruginosa (PA01 and PA124). Dried and fresh extracts from C. guanhumi displayed an antibacterial activity against 40% and 20% of the bacteria tested, respectively, whereas dried extracts from G. campestris and fresh extracts from T. hermanni inhibited the growth of 15% and 10% of bacteria, respectively (MIC range of 512 to 2048 µg/mL). The dried and fresh extracts of R. jimi, at MIC/2 and MIC/4, potentialized the activities of more than 70% of the antibiotics respectively against more than 70% of studied bacteria. Both extracts highly improved the activity of oxacillin, gentamicin, erythromycin, and ciprofloxacin with improved activity factors (IAFs) ranging from 16 to 256. Conclusion: This work demonstrated that R. jimi extracts had a broad spectrum of antibacterial activities. The overall data provided evidence that animals investigated in this study might be potential sources of natural antimicrobial agents; They can be combined with clinically used antibiotics to overcome bacterial resistance. Keywords: Animal extract, antibiotics; Gram-negative bacteria; efflux pumps; multidrug resistance; Rhinella jimi.

Background: Bacterial infections, especially those caused by multidrug-resistant (MDR) Gram-negative bacteria, remain a global health concern. Previous studies have reported the antibacterial activities of the methanol extract of the leaves of Acacia polyacantha Willd. (Fabaceae) (APL) as well as some of its phytoconstituents. In this study, APL and its constituent, 3-O-[β-galactopyranosyl-(1→4)-β-D-galactopyranosyl]-oleanolic acid (GGOA) were evaluated on growth kinetics, bacterial membrane, and H+-ATPase proton pumps. The acute toxicity of APL was also studied. Methods: The effects of APL and GGOA on bacterial growth kinetics and the bacterial membrane was determined using spectrophotometric methods. Their effects on the bacterial H+-ATPase proton pumps were evaluated through the acidification of the bacterial external environment using a pH-meter. The acute toxicity of APL was determined using the standard limit test method described by the Organization for Economic Cooperation and Development (OECD) code 425. Results: APL and GGOA modified the bacterial kinetics of Providencia stuartii ATCC29916 with emphasis on the latent phase. They blocked the proton pumps of this bacterium and destroy the bacterial membrane. The medium lethal dose (LD50) of APL was greater than 5000 mg/kg body weight (b.w.). Conclusion: The results of the present study provide important and complementary information on APL and GGOA as good antibacterial candidates for combating infections due to MDR Gram-negative bacteria. Keywords: 3-O-[β-galactopyranosyl-(1→4)-β-D-galactopyranosyl]-oleanolic acid; Acacia polyacantha; acute toxicity; Gram-negative bacteria; mode of action; multidrug resistance.

Rumex abyssinicus Jacq. is a perennial medicinal herb widely used in traditional medicine to treat many diseases. Phytochemicals of the plant were isolated using column chromatography and thin layer chromatography techniques. Extract, fractions and pure compounds were screened for antimicrobial activity against sensitive and multi-drug resistant microbes and their cytotoxicity was performed on different cancer cell lines. The mechanism of action of purified helminthosporin as well as the potent fraction containing a mixture of two compounds was assessed. Fraction R7C3 was the most potent antibacterial with the lowest MIC value of 0.12 µg/mL. Helminthosporin was the most potent compound with the lowest MIC value of 1.95 µg/mL. The compound was more potent than the antibiotic chloramphenicol against multi-drug resistant (MDR) bacteria with MIC equal to 16 µg/mL. The fraction and helminthosporin were shown to destroy the cell wall of the yeast and bacteria, and DNA fragmentation effect on the genome of Candida albicans and Bacillus cereus . Helminthosporin was the most cytotoxic compound with IC 50 ˂ 10 µM. Fraction R7C3 showed the most potent cytotoxic effects on all cancer cell lines, with IC 50 ranging from ˂1 to 4.35 ng/mL. Our study is the first report on the mechanism of action of helminthosporin, a potent candidate in the development of new drugs against multi-resistant bacteria and cancer cells. In addition, this study uncovered Rumex abyssinicus as a new source of syringic acid and bis(2-ethyloctyl) phthalate.

Background: Medicinal plants have always played an important role in human health. Many plants are traditionally used as drugs against microbial infections. In this study, a panel of seven methanol extracts from Cameroonian edible was assessed for their antibacterial potentiality against multidrug-resistant Gram-positive and Gram-negative bacteria. Methods: The microdilution technique using a 96-well plate was used to assess the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of the crude extracts, as well as their potential to improve the antimicrobial activity of certain families of antibiotics. Phytochemical screening of the extracts was carried out according to the standard methods. Results: The most detected classes of pharmaceuticals were tannins, triterpenes, polyphenols, and steroids. Coffea arabica bark extract inhibited all 20 tested MDR bacteria strains; Coffea arabica leaf and seeds extracts, Adansonia digitata bark extract, Sechium edule leaf extract, all inhibited 95% (19/20) of the strains tested, Beilschmeidia louisii stem extract inhibited the growth of 85% (17/20) of the tested bacteria, while Hyphaene therbaica displayed 70% (14/20) bacterial inhibition. The MIC values of the plant extracts ranged from 256 to 2048 μg/mL. However, the best MIC value (256 μg/mL) was obtained with B. louisii stem extract against E. coli AG102 and S. aureus MRSA12. The leaf extract of S. edule improved the anti-bacterial activities of kanamycin, tetracycline, and Cloxacillin against the MDR strain P. stuartii 29916 by up to 16 times; furthermore, this extract improved the antibacterial effect of tetracycline, Cloxacillin, kanamycin, and doxycycline by 16 folds against the MDR strain E. coli AG100ATET; the bark extract of C. arabica improved the activities of ofloxacin, chloramphenicol the activities of ofloxacin, chloramphenicol, and doxycycline toward all the tested MDR Gram positive and Gram-negative bacteria with improvement activity factor (IAF) ranging from 2 to 16, while the leaf extract of B. louisii increased up to 8-fold the activity of Cloxacillin against P. aeruginosa PA 124. Conclusion: Coffea arabica, Adansonia digitata, Sechium edule, and Beilschmeidia louisii are the explorable sources of antibacterial agents usable alone or in combination with conventional antibiotics to tackle diseases caused by resistant bacterial phenotypes. Keywords: Bacterial infections; Cameroon; edible plants; Multidrug resistance; Antibiotic-potentiation.

In this study, we examined the antibacterial and antibiotic-resistance reversal properties of methanol (MeOH) and ethyl acetate (EtOAc) extracts and compounds from Psychotria sycophylla aerial parts against drug-resistant bacteria. The tests were performed using the microdilution method. The mechanisms of action were investigated on growth kinetic and proton pumps of Escherichia coli. The structures of isolated compounds including oleanolic acid (1), ursolic acid (2), lupeol (3), betulinic acid (4), β-sitosterol glucoside (5), and stigmasterol (6), were established based on nuclear magnetic resonance (NMR) and electrospray ionization-mass spectrometry (ESI–MS). The extracts displayed noteworthy antibacterial activities, with recorded minimal inhibitory concentrations (MIC) ranging from 4 to 1024 µg/mL. Significant activities (MIC < 100 µg/mL) were obtained with the MeOH extract against Providencia stuartii PS2636 and Staphylococcus aureus MRSA9 (MIC of 16 µg/mL) as well as the EtOAc extract against S. aureus MRSA3 (MIC of 32 µg/mL) and Enterobacter aerogenes EA27 (MIC of 4 µg/mL). MeOH extract displayed a broad-spectrum antibacterial activity, acting against 21 out of 22 studied bacteria. The MICs of compounds (1–6) varied from 16 to 256 µg/mL. Oleanolic acid (1) appeared to be the most effective, preventing the growth of 100

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.

Ethnopharmacological relevance: Infections due to multidrug-resistant (MDR) bacteria constitute a real problem in the public health worldwide. Hypericum roeperianum Schimp. ex A. Rich (Hypericaceae) is used traditionally for treatment of various ailments such as abdominal pains, constipation, diarrhea, indigestion, nausea, and bacterial diseases. Aim of the study: This study was aimed at investigating the antibacterial and antibiotic-modifying activity of the crude methanol extracts (HRB), ethyl-acetate soluble fraction (HRBa), residual material (HRBb), and 11 compounds from the bark of Hypericum roeperianum against multi-drug resistant (MDR) bacteria expressing active efflux pumps. Materials and methods: The antibacterial activity, the efflux pump effect using the efflux pump inhibitor (EPI), phenylalanine-arginine-ss-naphthylamide (PA beta N), as well as the antibiotic-modifying activity of samples were determined using the broth micro-dilution method. Spectrophotometric methods were used to evaluate the effects of HRB and 8,8-bis(dihydroconiferyl) diferulate (11) on bacterial growth, and bacterial membrane damage, whereas follow-up of the acidification of the bacterial culture was used to study their effects on bacteria protonATPase pumps. Results: The crude extract (HRB), HRBa, and HRBb had selective antibacterial activity with MICs ranging from 16 to 512 mu g/mL. Phytochemical 11 displayed the best antibacterial activity (0.5 < MIC < 2 mu g/mL). The activity of HRB and 11 in the presence of EPI significantly increased on the tested bacteria strains (up to 32-fold). The activity of cloxacillin (CLO), doxycycline (DOX), and tetracycline (TET), was considerably improved (up to 64fold) towards the multidrug-resistant Enterobacter aerogenes EA-CM64 strain. The crude extract (HRB) and 11 induced the leakage of bacterial intracellular components and inhibited the proton-ATPase pumps.

Ethnopharmacological relevance: Piper capense is a medicinal spice whose fruits are traditionally used as aqueous decoction to heal several ailments such as trypanosomiasis, helminthic infections, and cancer. Aim of the study. (1) To perform phytochemical investigation of the methanol extract of Piper capense; (2) to evaluate the cytotoxicity of botanicals (PCF, fractions PCFa-e), isolated phytochemicals on a broad panel of animal and human cancer cell lines; (3) to evaluate the induction of apoptosis of the most active samples. Material and methods: Resazurin reduction assay (RRA) was used to determine the cytotoxicity of the studied samples. Cell cycle distribution (PI staining), apoptosis (annexin V/PI staining), mitochondrial membrane potential (MMP; JC-1) and reactive oxygen species (ROS; H2DCFH-DA) were measured by flow cytometry. Column chromatography (CC) was used for the purification of PCF, whilst nuclear magnetic resonance (NMR) spectroscopic and mass spectrometric (MS) analyses were applied for structural elucidation. Results: The phytochemical investigation of PCF led to the isolation of 11 compounds: licarin B (1), licarin A (2), 7-(1,3-benzodioxol-5-yl)-7,8-dihydro-8-methyl-5-(2-propenyl)-furo [3,2-e]-1,3-benzodioxole (3), nitidine isocyanate (4), 5-hydroxy-7,4'-dimethoxyflavone (5), cardamomin (6), sitosteml (7) and stigmasteml (8), beta-sitosterol 3-O-beta-D-glucopyranoside (9), oleanolic acid (10) and lupeol (11). Fraction PCFb, compound 2 and doxorubicin (as positive control drug) revealed cytotoxic effects towards the 18 tested cancer cell lines. The IC50 values ranged from 6.1 mu g/mL (against CCRF-CEM cells) to 44.2 mu g/mL (against BRAF-V600E homozygous mutant melanoma cells) for PSCb; from 4.3 mu M (against CCRF-CEM cells) to 21.8 mu M (against HCT116 p53(-/-)) for compound 2 and from 0.02 mu M (against CCRF-CEM cells) to 123.0 mu M (against CEM/ADR5000 cells) for doxorubicin. PCFb and compound 2 induced apoptosis in CCRF-CEM cells mediated by activation of caspase 3/7, 8 and 9, MMP alteration and increased ROS production. Conclusion: Piper capense is a source of potent cytotoxic botanicals and phytochemicals that could help to fight various types of cancer including multidrug resistance phenotypes. PCFb and compound 2 should further be explored to develop new drugs to fight malignancies.

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, PA β N) 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  μ g/mL, whereas its fractions showed MICs varying from 32 to 512  μ g/mL on the studied bacteria. Fraction C of P. glandulosus showed the lowest MIC (32  μ g/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 PA β N 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.

Piper capense belongs to Piperaceae family and has long been used as a traditional medicine to treat various diseases in several parts of Africa. The present study aims to investigate the effect of Piper capense fruit extract (PCFE) alone and in combination with dacarbazine on metastatic melanoma cell line B16-F10 and in vivo in C57BL/6J mice. Cytotoxic effects of PCFE alone and in association with dacarbazine on B16-F10 cells were studied by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay and colony formation assay. Wound healing assay, immunofluorescence staining, and western blot analysis were performed to evaluate the individual and combined effect of PCFE and dacarbazine on epithelial-mesenchymal transition (EMT). For in vivo studies, C57BL/6J mice were subcutaneously injected with B16-F10 cells (5 × 105 cells/mL), and the effect of PCFE and dacarbazine was studied on tumor development. The alteration of EMT was evaluated by targeting E-cadherin, vimentin, and CD133 in PCFE alone and in combination with dacarbazine-treated tumor tissues by western blot analysis. Phytochemical screening of PCFE reveals the presence of certain secondary metabolites. Our results showed that PCFE alone and in association with dacarbazine has a good activity in preventing B16-F10 melanoma cell progression and clonogenicity. This extract also regulated EMT. In vivo results showed that PCFE (100 mg/kg body weight) reduced tumor size in C57BL/6J mice along with the decrease in the expression of vasculogenic mimicry (VM) tubes as well as an improvement in the qualitative and quantitative expression of markers involved in EMT. Our study suggests that PCFE may be useful for managing the growth and metastasis of melanoma.

The chemical investigation of Anonidium mannii root extract by column chromatography techniques led to the isolation of eight compounds among which two previously unreported compounds; a lanostane-type triterpene, lanosta-7,9(11),23-triene-3 beta,15 alpha-diol 1 and an alkaloid, 9-hydroxy-8-methoxyphenanthridin-6(5H)-one 2 along with six known compounds: lanosta-7,9(11),24-triene-3 beta,21-diol 3, oxoanolobine 4, 3, 4-dihydroxybenzoic acid 5, stigmasterol 6, beta-sitosterol 7 and 3-O-beta-D-glucopyranosyl-beta-stigmasterol 8. Their structures were established from spectral data, mainly HR-ESIMS, 1 D and 2 D NMR and by comparison with literature data. The crude root and stem bark extracts (AMR and AMB) and the isolated compounds (1-8) were tested against nine Gram-negative bacteria using rapid p-iodonitrotetrazolium chloride >= 97% (INT) microdilution technique. It was found that AMR, AMB and compound 5 were active against the nine tested bacteria with MIC values ranging from 64 to 1024 mu g/mL. Compounds 1-4 had selective antibacterial activities whilst 6-8 were not active.

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.

Abstract Background: Bacterial infections involving the multidrug resistant (MDR) strains are among the top leading causes of death throughout the world. Healthcare system across the globe has been suffering from an extra-ordinary burden in terms of looking for the new and more potent antimicrobial compounds. The aim of the present study was to determine the antibacterial activity of some Cameroonian edible plants (Garcinia lucida bark, Phoenix dactylifera pericarps, Theobroma cacao pod, Solanum macrocarpon leaves and Termitomyces titanicus whole plant) and their antibiotics-potentiation effects against some MDR Gram-negative bacteria phenotypes expressing efflux pumps (Escherichia coli, Enterobacter aerogenes, Klebsiella pneumoniae, Pseudomonas aeruginosa and Providencia stuartii strains). Methods: The antibacterial activities of plant extract alone and in combination with usual antibiotics were carried out using the micro-dilution method. The effects of the most active plant extract (Garcinia lucida bark) on H+-ATPase-mediated proton pumps and on bacterial growth kinetic were performed using experimental protocols, while qualitative reference methods were used to highligh the major groups of secondary metabolites present in the extracts. Results: Qualitative phytochemical screening of plant extracts indicated that all analysed secondary metabolites were present in Theobroma cacao and Termitomyces titanicus while one (saponins) of them was absent in Garcinia lucida and Solanum macrocarpon. Only three of them (polyphenols, flavonoids and saponins) were detected in Phoenix dactylifera. Antibacterial essays showed that G. lucida was the most active plant as it inhibited the growth of all studied bacteria with strong activity (MIC<100 µg/mL) against E. coli ATCC8739, significant activity (100≤MIC≤512 µg/mL) against 80% of bacteria and moderate activity (512

Abstract Background: In recent years, drug resistance to human pathogenic bacteria has been commonly reported from all over the world. As antimicrobial activities of most medicinal plants and antibiotics have been already explored, it is more important to make investigations on animal species mainly invertebrates which could constitute an efficient source of antimicrobial molecules. This work was aimed at contributing to the fight against microbial resistance through the study of antibacterial potential of three animal species (Helix aspersa, Bitis arietans, Aristaeomorpha foliacea) on several multidrug-resistant (MDR) Gram-negative strains overexpressing efflux pumps including Escherichia coli, Enterobacter aerogenes, Klebsiella pneumoniae, Pseudomonas aeruginosa. Methods: The microdilution technique was used to evaluate the antibacterial activities of the tested samples by determining their minimal inhibitory concentrations (MICs), as well as the effect of their combination with antibiotics. Studies on the mechanisms of action of the most active sample, dried Bitis arietans extract, was carried out using standard methods for evaluating the effects of this extract on bacterial H+-ATPases-mediated proton pumps and on bacterial growth kinetics. In this latter case, the optical density was read spectrophotometrically. Results: Zoochemical screening indicated the presence of protein constituents and alkaloids and the absence of other metabolites in all tested extracts. Dried B. arietans showed the best antibacterial activity by inhibiting the growth of 90% of studied bacterial strains with MICs ranging from 128 to 2048 μg/ml. Moreover, this extract presented a significant activity (100≤MIC≤512 µg/ml) against 35% of bacteria that are E. coli (ATCC8739, AG100ATet, MC4100), E. aerogenes EA27, K. pneumoniae ATCC11296, P. aeruginosa (PA01, PA124) and a moderate activity (512

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 1 H and 13 C 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.