BackgroundCandida albicans is one of the organisms living on the human body symbiotically, but, in hosts with low immunity it becomes one of the most pathogenic fungal organisms. Combretum zeyheri has been reported to have antifungal, antibacterial and antioxidant activities. Medicinal plants are believed to be non-toxic by the general public. Toxicity studies, however, have indicated that they are capable of causing numerous side effects, therefore, evaluation of safety is required. The objective of this study was to determine the toxicity of the antifungal constituents of Combretum zeyheri on mammalian cells.MethodsAlkaloids, saponins, flavonoids-enriched extracts and crude ethanol extracts were prepared from the leaves of Combretum zeyheri. The broth microdilution method was used to investigate for antifungal activity, with miconazole used as the positive control. The MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was used to determine cell viability of the Candida albicans cells. The most potent extracts; the ethanol extract, alkaloids and saponins respectively, were further tested for their toxicity on sheep erythrocytes, mouse peritoneal macrophages and Jurkat T cells.ResultsAll Combretum zeyheri extracts displayed a dose-dependent antifungal activity and had IC50 values ranging from 16 μg/ml to 159 μg/ml for Candida albicans. The alkaloids, saponins and ethanol extracts were found to be non-toxic towards mouse peritoneal cells and Jurkat T cells. In the haemolysis assay, all extracts were haemolytic at varying degrees and showed their greatest haemolytic activity at the highest concentration of 5 mg/ml. The saponins were the least haemolytic, followed by the ethanol extracts and the alkaloids respectively. Although these extracts were haemolytic to some extent, they may considered safe at therapeutic concentrations since there was a large difference between the antifungal IC50 and haemolysis EC50 values, hence a large therapeutic window.ConclusionsCombretum zeyheri antifungal constituents are, therefore, a potential source of lead compounds which can be developed into antifungal drugs of natural origin owing to Combretum zeyheri’s effective antifungal activity and low toxicity to mammalian cells.

Despite plants being a rich source of useful chemical compounds with different pharmacological properties, some of these compounds may be toxic to humans. Parinari curatellifolia, among its other important pharmacological activities, has been shown to have significant antiproliferative activity on cancer cell lines. Toxicity studies are required to determine the safety profile of P. curatellifolia in the consideration of its potential pharmaceutical benefits as a source of lead compounds in cancer therapy. The effects of P. curatellifolia on both the integrity of the erythrocyte membrane and on normal cells were determined. The dried leaf powder of P. curatellifolia was used in serial exhaustive extraction procedures using hexane, dichloromethane, ethyl acetate, acetone, ethanol, methanol, and water as solvents in addition to extraction using DCM: methanol in equal ratio. Alkaloids, flavonoids, and saponins were isolated from the ethanol extract. The leaf extracts were tested for haemolytic activity on sheep erythrocytes at concentrations of 0.625 to 5 mg/ml. The extracts were also tested for toxicity activity on normal mammalian cells such as the BALB/c mice peritoneal cells using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) at the concentrations of 6.3 to 50 μg/ml. In the haemolysis assays, none of the plant extracts had a significant haemolytic activity with the saponin-enriched extract having the maximum haemolytic activity of 12.2% for a concentration of 5 mg/ml. In the MTT cell viability assay, none of the 11 plant extracts had significant cytotoxicity. The water extract, however, had significant ( p < 0.01 ) proliferative activity towards the murine immune cells at all concentrations. P. curatellifolia leaf extracts were, therefore, not toxic to both erythrocytes and immune cells, and the water extract may have immunostimulatory effects. It is concluded that P. curatellifolia leaf extracts are not toxic in vitro and, therefore, our results support the use of the plant for ethnomedicinal use.

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Combretum zeyheri and Combretum platypetalum have been shown to have anticancer, antibacterial, antituberculosis, and antifungal effects in both in vivo and in vitro studies. This study sought to evaluate the antiproliferative effects of compounds isolated from C. zeyheri and C. platypetalum on Jurkat T and HL-60 cancer cell lines in combination with doxorubicin and/or chlorambucil. At their GI50 concentrations, the isolated compounds were combined with the corresponding GI50 of chlorambucil and doxorubicin. The cytotoxic effects of the combined compounds were determined on BALB/c mouse peritoneal cells. All the 4 isolated compounds had significant cytotoxic effects on Jurkat T cells. Compounds CP 404 (1), CP 409 (2), CZ 453 (3), and CZ 455 (4) had GI50s on Jurkat T cells of 3.98, 19.33, 6.82, and 20.28 μg/ml, respectively. CP 404 (1), CP 409 (2), CZ 453 (3), and CZ 455 (4) showed GI50s of 14.18, 28.69, 29.87, and 16.46 μg/ml on HL-60 cancer cell lines, respectively. The most potent combination against Jurkat T cells was found to be CP 404 (1) and chlorambucil. This combination showed no cytotoxic effects when tested on BALB/c mouse peritoneal cells. It was concluded that the compounds extracted from C. zeyheri and C. platypetalum inhibit the growth of Jurkat T cells in vitro. The combination of the compounds with anticancer drugs enhanced their anticancer effects. The combination of CP 404 (1) and chlorambucil was found not to be toxic to normal mammalian cells. Therefore, CP 404 (1), 3-O-β-L-rrhamnopyranosyl-5,7,3 ′ 4 ′ ,5 ′ -pentahydroxyflavone, has the potential to be a source of lead compounds that can be developed for anticancer therapy. Further structure-activity relationship studies on this compound are warranted.

ESKAPE pathogens, namely, Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species, are responsible for a majority of all healthcare-acquired infections (HAI). The bacteria cause nosocomial infections in immunocompromised patients. Extracts from Callistemon viminalis have been shown to have antibacterial, antifungal, and anti-inflammatory activities. Tormentic acid congener, a pentacyclic triterpene saponin, was isolated from C. viminalis leaves. This study aimed to investigate the antibacterial effects of tormentic acid congener and leaf extracts on biofilm formation by A. baumannii, S. aureus, S. pyogenes, and P. aeruginosa. The antibacterial effects were determined by the microbroth dilution method, and ciprofloxacin was used as the standard antibacterial drug. Biofilm formation and detachment assays were performed using crystal violet staining. Production of extracellular polymeric DNA and polysaccharides from biofilms was also determined. Tormentic acid congener showed time-dependent antibacterial activity against P. aeruginosa with a MIC of 100 µg/ml and caused significant protein leakage. Antibacterial activity was found when tormentic acid congener was tested against both S. aureus and P. aeruginosa. The MICs were found to be 25 µg/ml and 12.5 µg/ml for P. aeruginosa and S. aureus cells, respectively. S. pyogenes was found to be susceptible to tormentic acid congener and the hydroethanolic extract with an MIC of 100 µg/ml and 25 µg/ml, respectively. A. baumannii was found not to be susceptible to the compound or the extracts. The compound and the extracts caused a significant decrease in the biofilm extracellular polysaccharide content of S. pyogenes. The extracts and tormentic acid congener caused detachment of biofilms and decreased the release of extracellular DNA and capsular polysaccharides from biofilms of P. aeruginosa and S. aureus. Tormentic acid congener and extracts, thus, have significant antibacterial and antibiofilm activities on these selected ESKAPE bacteria and can act as source lead compounds for the development of antibacterial triterpenoids.