Anti-yeast activity of extracts and fractions from Uvariodendron calophyllum (Annonaceae)

The resistance to available antifungals highlights the urgent need for innovative drugs to treat yeasts infections. This study aimed at evaluating the activity of extracts and fractions from Uvariodendron calophyllum against pathogenic yeasts. The ethanolic and aqueous extracts obtained by maceration were liquidliquid- partitioned using organic solvents and screened against isolates of Candida albicans, Candida glabrata, Candida parapsilosis, Cryptococcus neoformans and Candida albicans reference strains NR-29445, NR-29444, NR-29451, and NR-29450 from BEI Resources using the broth micro-dilution method. Time kill kinetic, inhibition of germ-tube, filamentation and chlamydosporulation, and biofilm formation were assessed using the best sub-fraction. Overall, the most interesting sub-fraction (FS: 237–253) showed an MIC value of 0.0625 mg/mL with cidal effect against C. albicans NR-29450 and NR-29445 at 0.25 mg/mL after 12-16 hours and 24 hours respectively. Moderate inhibitory effects were observed at 0.25 mg/mL against germ-tube formation, filamentation and chlamydosporulation of all C. albicans strains. Also, very moderate inhibition of biofilm formation by C. albicans NR-29450 at 0.25 mg/mL was obtained. The results obtained support U. calophyllum as a potential source of compounds with anti-yeast activity. Further studies will confirm its potential as source of anti-yeast drugs.© 2015 International Formulae Group. All rights reserved.Keywords: Uvariodendron calophyllum, anti-yeasts activity, time kill kinetics, biofil

Endophytic Fungi from <i>Terminalia</i> Species: A Comprehensive Review

Endophytic fungi have proven their usefulness for drug discovery, as suggested by the structural complexity and chemical diversity of their secondary metabolites. The diversity and biological activities of endophytic fungi from the Terminalia species have been reported. Therefore, we set out to discuss the influence of seasons, locations, and even the plant species on the diversity of endophytic fungi, as well as their biological activities and secondary metabolites isolated from potent strains. Our investigation reveals that among the 200&#8722;250 Terminalia species reported, only thirteen species have been studied so far for their endophytic fungi content. Overall, more than 47 fungi genera have been reported from the Terminalia species, and metabolites produced by some of these fungi exhibited diverse biological activities including antimicrobial, antioxidant, antimalarial, anti-inflammatory, anti-hypercholesterolemic, anticancer, and biocontrol varieties. Moreover, more than 40 compounds with eighteen newly described secondary metabolites were reported; among these, metabolites are the well-known anticancer drugs, a group that includes taxol, antioxidant compounds, isopestacin, and pestacin. This summary of data illustrates the considerable diversity and biological potential of fungal endophytes of the Terminalia species and gives insight into important findings while paving the way for future investigations

Garcinia kola (Heckel) and Alchornea cordifolia (Schumach. & Thonn.) Müll. Arg. from Cameroon possess potential antisalmonellal and antioxidant properties.

Drug resistant Salmonella species and shortcomings related to current drugs stress the urgent need to search for new antimicrobial agents to control salmonellosis. This study investigated the antisalmonellal and antioxidant potentials of methanolic and hydro-ethanolic extracts of Garcinia kola and Alchornea cordifolia as potential sources of drugs to control Salmonella species and to reduce related oxidative stress. The antisalmonellal activity was assessed using the broth microdilution, membrane destabilization and time-kill kinetic assays. While, the DPPH, ABTS and FRAP assays were used for the determination of the antioxidant activities. The minimum inhibitory concentrations ranged from 125 to 1000 μg/mL, with the methanolic root extract of G. kola being the most active. The time kill kinetic assay revealed a concentration-dependent bacteriostatic activity for promising extracts. Potent extracts from G. kola showed the ability to destabilize S. typhi outer membrane, with the methanolic root extract presenting the highest activity; two-fold higher than those of polymyxin B tested as reference. In addition, this methanolic root extract of G. kola also provoked nucleotide leakage in a concentration-dependent manner. From the antioxidant assays, the hydro-ethanolic extract from the stem bark of A. cordifolia presented significant activities comparable to that of Vitamin C. The methanolic root extract of G. kola also presented appreciable antioxidant activities, though less than that of A. cordifolia. Overall, the phytochemical screening of active extracts revealed the presence of anthocyanins, flavonoids, glycosides, phenols, tannins, triterpenoids and steroids. These results provide evidence of the antibacterial potential of G. kola and offer great perspectives in a possible standardisation of an antisalmonellal phytomedicine

Crude metabolites from endophytic fungi inhabiting Cameroonian Annona muricata inhibit the causative agents of urinary tract infections.

Urinary tract infections (UTIs) are common bacterial infections. The global emergence of multidrug-resistant uropathogens in the last decade underlines the need to search for new antibiotics with novel mechanisms of action. In this regard, exploring endophytic fungi inhabiting medicinal plants used locally against urinary tract infections could be a promising strategy for novel drug discovery. This study investigates crude metabolites from endophytic fungi isolated from Annona muricata as potential sources of antibiotic drugs to fight against uropathogens and reduce related oxidative stress. Crude ethyl acetate extracts from 41 different endophytic fungi were screened against three bacterial strains using the broth microdilution method, and fungi producing active crude extracts were identified using ITS1-5.8S rRNA-ITS2 nucleotide sequences. The antibacterial modes of action of the five most active extracts were evaluated using Staphylococcus aureus ATCC 43300 and Klebsiella oxytoca strains. The DPPH and FRAP assays were used to investigate their antioxidant activity, and their cytotoxicity against the Vero cell line was evaluated using the MTT assay. Out of the 41 crude extracts tested, 17 were active with minimum inhibitory concentrations (MICs) ranging from 3.125 μg/mL to 100 μg/mL and were not cytotoxic against Vero cell lines with a cytotoxic concentration 50 (CC50) >100 μg/mL. The more potent extracts (from Fusarium waltergamsii AMtw3, Aspergillus sp. AMtf15, Penicillium citrinum AMf6, Curvularia sp. AMf4, and Talaromyces annesophieae AMsb23) significantly inhibited bacterial catalase activity, lysed bacterial cells, increased outer membrane permeability, and inhibited biofilm formation, and the time-kill kinetic assay revealed concentration-dependent bactericidal activity. All seventeen extracts showed weak ferric iron-reducing power (1.06 to 12.37 μg equivalent NH2OH/g of extract). In comparison, seven extracts exhibited DPPH free radical scavenging activity, with RSA50 ranging from 146.05 to 799.75 μg/mL. The molecular identification of the seventeen active fungi revealed that they belong to six distinct genera, including Aspergillus, Curvularia, Fusarium, Meyerozyma, Penicillium, and Talaromyces. This investigation demonstrated that fungal endophytes from Cameroonian Annona muricata, a medicinal plant used locally to treat bacterial infections, might contain potent antibacterial metabolites with multiple modes of action. The antibacterial-guided fractionation of these active extracts is currently ongoing to purify and characterise potential antibacterial active ingredients

Cytotoxicity Potential of Endophytic Fungi Extracts from Terminalia catappa against Human Cervical Cancer Cells

Endophytic fungi are potential sources of novel bioactive metabolites from a natural product drug discovery perspective. This study reports the bioactivity-directed fractionation of the secondary metabolites of the ethyl acetate extract of a fermentation culture of endophytic fungi from Terminalia catappa which were then evaluated for their cytotoxicity against human cervical cancer (HeLa) cells and human foreskin fibroblast (HFF) cells. Furthermore, apoptosis was determined using the Annexin V/propidium iodide (PI) flow cytometry assay. Endophyte extracts N2, N7, N8, N97, N169, and N233 were obtained from Trichoderma sp, Phoma sp, Phomopsis phyllanticola, Fusarium oxyporum, Collectotrichum sp, and Cryptococcus flavescens, respectively. The N97 extract was most active with a 50% inhibitory concentration (IC50) of 33.35 µg/ml. A 50% cytotoxic concentration (CC50) of 268.4 µg/ml was obtained with HFF cells and the selectivity index (SI) was 8.01. The percentages of cell populations were increased at late apoptosis (Annexin+/PI+), with the percentages of 27.4 ± 0.3 and 19.2 ± 0.01 obtained, respectively, for 50 µg/ml and 80 µg/ml of the N97 extract and 2.1 ± 0.1 obtained for the control in late apoptosis (Annexin V+/PI+) . Moreover, a higher reduction in the percentage of viable cells was observed in the HeLa control cells (93.6 ± 0.3), but the percentages of viable HeLa cells were 37 ± 0.05 and 45 ± 0.1, respectively, for the 50 µg/ml and 80 µg/ml treatments with the N97 extract. Also, the percentages of 34.7 ± 0.1 and 33.9 ± 0.4 were, respectively, obtained for 50 µg/ml and 80 µg/ml compared to the control with 4.6 ± 0.2, in early apoptosis (Annexin V+/PI-). These findings highlight the anticancer potential of the N97 extract of endophytic fungi from Terminalia catappa, which is mediated through apoptosis and presumably also attenuation of chemoresistance

Antiplasmodial and cytotoxic activity of lanostane type triterpenoids isolated from Leplaea mayombensis

International audienceLeplaeric acid E 5, leplazarin 6a and 21-epileplazarin 6b, three new 3,4-seco-lanostane type triterpenes have been isolated from the stem bark of Leplaea mayombensis (Pellegr.) Staner along with fourteen known compounds from the fruits and roots. Leplaeric acid E, leplazarin and 21-epileplazarin, 15-α-hydroxy-3,4-seco-lanosta-4(28),8,24-triene-3,21-dioic acid, mayomlactones A and B, lanosta-7,24-dien-3-one, leplaeric acid A, B and C were screened in vitro for antiplasmodial activity against chloroquine-sensitive (Pf3D7) and chloroquine-resistant (PfINDO) strains of Plasmodium falciparum and for cytotoxicity against CAL-27, CaCo2, Skov-3, and HepG2 cells line. Three compounds including 15-α-hydroxy-3,4-seco-lanosta-4(28),8,24-triene-3,21-dioic acid (IC50 5.65–7.09 μM), lanosta-7,24-dien-3-one (IC50 7.18–9.07 μM), and leplaeric acid C (IC50 7.59–8.47 μM) were the most active against both strains of P. falciparum. All the compounds exhibited cytotoxicity against the three-cell lines with IC50 ranging from 12.30 to 181.88 μM. These results confirm the usage of the medicinal plant L. mayombensis for the management of malaria and suggest that further lead optimization studies on potent compounds identified from this study could lead to the identification of potential of lead molecules as scaffold for new antimalarial drug discovery

Antibacterial and Mode of Action of Extracts from Endophytic Fungi Derived from Terminalia mantaly, Terminalia catappa, and Cananga odorata

Mbekou MIK, Dize D, Yimgang VL, et al. Antibacterial and Mode of Action of Extracts from Endophytic Fungi Derived from Terminalia mantaly, Terminalia catappa, and Cananga odorata. BioMed research international. 2021;2021: 6697973.Emerging drug-resistant bacteria creates an urgent need to search for antibiotics drugs with novel mechanisms of action. Endophytes have established a reputation as a source of structurally novel secondary metabolites with a wide range of biological activities. In the present study, we explore the antibacterial potential of endophytic fungi isolated from different tissues of Terminalia mantaly, Terminalia catappa, and Cananga odorata. The crude ethyl acetate extracts of 56 different endophytic fungi were screened against seven bacterial strains using the broth microdilution method. The antibacterial modes of action of the most active extracts (04) were evaluated using E. coli ATCC 25922 and H. influenzae ATCC 49247 strains. Both the DPPH and FRAP assays were used to investigate their antioxidant activity, and their cytotoxicity against the Vero cell line was evaluated using the MTT assay. Out of the 56 crude extracts tested, about 13% were considered very active, 66% partially active, and 21% nonactive against all tested bacterial strains with MIC values ranging from 0.32mug/mL to 25mug/mL. The four more potent extracts (MIC 100mug/mL). Results from this investigation demonstrated that endophytes from Cameroonian medicinal plants might content potent antibacterial metabolites. The bioguided fractionation of these potent extracts is ongoing to isolate and characterise potential active ingredients. Copyright © 2021 Michele Ines Kanko Mbekou et al

Anti-<em>Plasmodium falciparum</em> Activity of Extracts from 10 Cameroonian Medicinal Plants

Background: In the midst of transient victories by way of insecticides against mosquitoes or drugs against malaria, the most serious form of malaria, caused by Plasmodium falciparum, continues to be a major public health problem. The emergence of drug-resistant malaria parasites facilitated by fake medications or the use of single drugs has worsened the situation, thereby emphasizing the need for a continued search for potent, safe, and affordable new antimalarial treatments. In line with this need, we have investigated the antiplasmodial activity of 66 different extracts prepared from 10 different medicinal plants that are native to Cameroon. Methods: Extracts were evaluated for their capacity to inhibit the growth of the chloroquine-sensitive (Pf3D7) and resistant (PfINDO) strains of P. falciparum using the SYBR green fluorescence method. The cytotoxicity of promising extracts against human embryonic kidney cells (HEK293T) mammalian cells was assessed by MTT assay. Results: The antiplasmodial activity (50% inhibitory concentration, IC50) of plant extracts ranged from 1.90 to &gt;100 μg/mL against the two strains. Six extracts exhibited good activity against both Pf3D7 and PfINDO strains, including cold water, water decoction, and ethyl acetate extracts of leaves of Drypetes principum (Müll.Arg.) Hutch. (IC503D7/INDO = 4.91/6.64 μg/mL, 5.49/5.98 μg/mL, and 6.49/7.10 μg/mL respectively), water decoction extract of leaves of Terminalia catappa L. (IC503D7/INDO = 6.41/8.10 μg/mL), and water decoction extracts of leaves and bark of Terminalia mantaly H.Perrier (IC503D7/INDO = 2.49/1.90 μg/mL and 3.70/2.80 μg/mL respectively). These promising extracts showed no cytotoxicity against HEK293T up to 200 μg/mL, giving selectivity indices (SIs) in the range of &gt;31.20–80.32. Conclusions: While providing credence to the use of D. principum, T. catappa, and T. mantaly in the traditional treatment of malaria, the results achieved set the stage for isolation and identification of active principles and ancillary molecules that may provide us with new drugs or drug combinations to fight against drug-resistant malaria

Potentiation effect of mallotojaponin B on chloramphenicol and mode of action of combinations against Methicillin-resistant Staphylococcus aureus.

Staphylococcus aureus, the causative agent of many infectious diseases has developed resistance to many antibiotics, even chloramphenicol which was the essential antibiotic recommended for the treatment of bacterial infection. Thus, other alternatives to fight against S. aureus infections are necessary; and combinatory therapy of antibiotics with natural compounds is one of the approaches. This study evaluated the activity of the combination of mallotojaponin B and chloramphenicol against Methicillin-resistant Staphylococcus aureus (MRSA). Antibacterial activities were evaluated by broth microdilution and the checkerboard methods. Modes of action as time-kill kinetic, Nucleotide leakage, inhibition and eradication of biofilm, and loss of salt tolerance were evaluated. Cytotoxicity was evaluated on Vero and Raw cell lines. Mallotojaponin B showed good activity against MRSA with a MIC value of 12.5 μg/mL. MRSA showed high resistance to chloramphenicol (MIC = 250 μg/mL). The combination produced a synergistic effect with a mean FICI of 0.393. This combination was bactericidal, inducing nucleotide leakage, inhibiting biofilm formation, and eradicating biofilm formed by MRSA. The synergic combination was non-cytotoxic to Vero and Raw cell lines. Thus, the combination of mallotojaponin B and chloramphenicol could be a potential alternative to design a new drug against MRSA infections