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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 FROM AUTHOR]

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 µg/mL; Excellent activity: 8 < MIC ≤ 40 µg/mL; Very good activity: 40 < MIC ≤ 128 µg/mL; Good activity: 128 < MIC ≤ 320 µg/mL; Average activity: 320 < MIC ≤ 625 µg/mL; Weak activity: 625 < MIC ≤ 1024 µg/mL; Not active: MIC values> 1024 µg/mL; (ii) For phytochemicals: Outstanding activity: MIC ≤ 2 µg/mL; Excellent activity: 2 < MIC ≤ 4 µg/mL; Very good activity: 4 < MIC ≤ 8 µg/mL; Good activity: 8 < MIC ≤ 32 µg/mL; Average activity: 32 < MIC ≤ 64 µg/mL; Weak activity: 64 < MIC ≤ 512 µg/mL; Not active: MIC> 512 µg/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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Acacia polyacantha is a medicinal plant traditionally used to treat livestock diseases and gastrointestinal infections; our study was undertaken to evaluate the antistaphylococcal activities of the methanolic leaf, bark, and root extracts, fractions, and compounds from Acacia polyacantha against a panel of 14 multidrug-resistant Staphylococcus bacterial strains overexpressing efflux pumps. The study was also extended to investigate two possible modes of action, that is, influence on bacterial growth kinetics and influence on proton-ATPase pumps, of the most active compound against a reference strain. Materials and Methods. The crude extracts after extraction were subjected to column chromatography. Antibacterial assays of extracts, fractions, and compounds alone and in the presence of efflux pump inhibitors were carried out using the broth microdilution method and the study of two mechanisms of action achieved by standard methods with the most active compound. Results. The phytochemical study of Acacia polyacantha leaves leads to the isolation of stigmasterol (1), β-amyrin (2), 3-O-methyl-D-chiro-inositol (3), epicatechin (4), quercetin-3-O-galactoside (5), 3-O-[β-D-xylopyranosyl-(1 ⟶ 4)-β-D-galactopyranosyl]-oleanolic acid (6), 3-O-[β-galactopyranosyl-(1⟶ 4)-β-D-galactopyranosyl]-oleanolic acid (7) and that of leaves lead to the isolation of lupeol (8) 2,3-dihydroxypropyltetracosanoate (9), and methyl-gallate (10). Leaf, root, and bark extracts inhibited 92.85% (13/14), 92.85% (13/14), and 71.43 % (10/14) of the tested bacteria strains, respectively, with minimum inhibitory concentration (MIC) varying between 16 and 1024 μg/mL. Fractions exhibited better activities compared to those of their extracts of origin, as their MICs ranged from 16 to 512 μg/mL, with fractions from leaves being more active than those obtained from barks. Compounds had varying activities; MICs varied from 16 to 512 μg/mL with compound 4 presenting the best activity as MICs ≤100 μg/mL were obtained against 11 of the tested bacteria. The activities of extracts, fractions, and compounds were improved in the presence of carbonyl cyanide m-chlorophenylhydrazone (CCCP) as an efflux pump inhibitor to as much as >128 folds. Meanwhile, in the presence of chlorpromazine as an efflux pump inhibitor, only the activity of compound 10 was improved on 10 of the tested bacteria strains. Compound 4 prolonged the lag phase of the growth kinetic in a concentration-dependent manner and equally inhibited the proton-ATPase pumps of the tested bacteria strains. Conclusion. The present study demonstrates the antistaphylococcal potential of Acacia polyacantha and its constituents to combat bacterial infections alone or in combination with efflux pump inhibitors. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The present study was designed to evaluate the antibacterial activities of methanol extracts of bark and leaves of Syzygium jambos, as well as their synergistic effects with selected antibiotics against drug-resistant Gram-positive and Gram-negative bacteria. The crude extracts were subjected to qualitative phytochemical screening; broth microdilution method was used for antibacterial assays. Phytochemical studies indicate that leaves and bark extracts contained polyphenols, anthraquinones, tannins, and steroids. Extract of the leaves was active against all the 26 strains of Staphylococcus aureus and all the 21 strains of Gram-negative bacteria tested, within the minimum inhibitory concentration (MIC) range of 32–512 μg/mL. The lowest MIC value of 32 μg/mL was obtained with extract of the leaves against Staphylococcus aureus MRSA9 strain. In Gram-negative bacteria, the lowest MIC value of 64 μg/mL was also obtained against Enterobacter aerogenes EA294 and Klebsiella pneumoniae K24 strains. Against S. aureus strains, antibiotic-modulating activity of extracts at MIC/2 towards more than 70% of the tested strains was obtained when leaves and bark extracts were tested in association with chloramphenicol (CHL). This was also the case when leaves extract was combined with CHL, kanamycin (KAN), tetracycline (TET), and erythromycin (ERY) and when bark extract was combined with ciprofloxacin (CIP), TET, and ERY against Gram-negative bacteria. In conclusion, this study demonstrated that Syzygium jambos has antibacterial and antibiotic-modulating activities. [ABSTRACT FROM AUTHOR]

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.

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 (PAβN), 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 proton-ATPase pumps., Results: The crude extract (HRB), HRBa, and HRBb had selective antibacterial activity with MICs ranging from 16 to 512 μg/mL. Phytochemical 11 displayed the best antibacterial activity (0.5 ≤ MIC ≤ 2 μg/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 64-fold) 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., Conclusions: The crude extract (HRB) and 8,8-bis(dihydroconiferyl)diferulate from the bark of Hypericum roeperianum are good antibacterial candidates that deserve further investigations to achieve antibacterial drugs to fight infections involving MDR bacteria., (Copyright © 2021 Elsevier B.V. All rights reserved.)

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., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Gravalain Nanmeni et al.)

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; H 2 DCFH-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), sitosterol (7) and stigmasterol (8), β-sitosterol 3-O-β- 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 IC 50 values ranged from 6.1 μg/mL (against CCRF-CEM cells) to 44.2 μg/mL (against BRAF-V600E homozygous mutant melanoma cells) for PSCb; from 4.3 μM (against CCRF-CEM cells) to 21.8 μM (against HCT116 p53 -/- ) for compound 2 and from 0.02 μM (against CCRF-CEM cells) to 123.0 μM (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., (Copyright © 2021 Elsevier B.V. All rights reserved.)

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 15 th 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., Competing Interests: The authors declare no conflict of interest., (© 2020 The Author(s).)

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  μ g/mL. However, some extracts were significantly active against certain bacterial strains: seeds extract of Theobroma cacao (64  μ g/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  μ g/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  μ g/mL ≤ MIC ≤ 2048  μ g/mL) to weak (MIC > 2048  μ g/mL) antibacterial activities against the tested bacteria. Furthermore, extracts of leaf of Tristemma hirtum and pericarp s 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.