Inhibitory Activity of Combretum zeyheri and its S9 Metabolites against Escherichia coli, Bacillus subtilis and Candida albicans

2016

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.

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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In vitro toxicity determination of antifungal constituents from Combretum zeyheri

Mapfunde

Sithole

2016

“…Combretum leprosum -derived triterpenes have been shown to have anti-inflammatory effects in mice [ 39 ]. Administration of Combretum zeyheri extracts to rats and subsequent isolation of metabolites, showed that the rat liver metabolites could inhibit the growth of microorganisms [ 40 ]. Using human recombinant hematopoietic prostaglandin D2 synthase (GST sigma), we have also shown that the Parinari curatellifolia leaf extract was the most potent plant extract (IC 50 = 3.8 μg/ml) to inhibit this enzyme in vitro [ 41 ].…”

Section: Introductionmentioning

confidence: 99%

In vivo and in vitro inhibition of rat liver glutathione transferases activity by extracts from Combretum zeyheri (Combretaceae) and Parinari curatellifolia (Chrysobalanaceae)

Gweshelo

Muswe

2016

BackgroundParinari curatellifolia and Combretum zeyheri are medicinal plants used in Zimbabwe and other Southern African countries for stomach ailments, fever, body aches, wound healing, cancer and tuberculosis. Glutathione transferases (GSTs) are mammalian enzymes that play a significant role in the detoxification and metabolism of many xenobiotic and endogenous compounds and as such can interact with many exogenous compounds including herbal medicines.The effects of Parinari curatellifolia and Combretum zeyheri leaf extracts on glutathione transferases of male Sprague–Dawley rats were investigated in vivo and in vitro after oral administration of either leaf ethanol or water extracts of each plant.MethodsFor Parinari curatellifolia, 18 male Sprague-Dawley rats were administered with 0, 500 and 1000 mg/kg body weight of the leaf extracts in corn oil or saline. Animals were sacrificed after 96 h and the kidney and liver samples were removed and used to prepare the cytosolic fractions. GST activity was determined using 1-chloro-2, 4-dinitrobezene. For Combretum zeyheri, twenty four male Sprague–Dawley rats were randomly divided into two groups. These two groups were further divided into three groups of four animals each. They were given either the aqueous or ethanol extract at doses of C. zeyheri at 0, 50 mg/kg body weight and 200 mg/kg body weight. The extracts were administered orally by oral gavage for four consecutive days and the rats were sacrificed by cervical dislocation on the fifth day.ResultsIn animals administered with C. zeyheri, GST activity was significantly increased by the 200 mg/kg aqueous extract in the kidneys and livers in vivo whilst the ethanolic extract at 200 mg/kg decreased enzyme activity significantly both organs. Both the ethanol and aqueous extracts inhibited GST activity in vitro with the ethanol extract being more potent inhibitor than ethacrynic acid, a standard GST inhibitor. The increased GST activity in vivo and versus inhibition in vitro suggests that metabolites may be responsible for the effects observed in vivo. For P. curatellifolia, a dose-dependent decrease in GST activity was observed in vivo for the animals given the aqueous extract but no changes were observed with the ethanol extract. There was a concentration-dependent inhibition of cytosolic GSTs when P. curatellifolia leaf extracts in vitro. The ethanol extract of P. curatellifolia exhibited GST-inhibitory activity in the liver with an IC50 value of 12 μg/mL and for ethacrynic acid, the IC50 was found to be 10 μg/mL. This showed that this extract was a potent inhibitor of GSTs in vitro.ConclusionsC. zeyheri had an inductive effect on GST activity when administered in aqueous solution but inhibited GST in vitro whilst P. curatellifolia inhibited GST activity in vivo. Induction of GSTs would be cytoprotective against the toxic effects electrophilic chemicals. Since GSTs are responsible for the synthesis of prostaglandins, the inhibition of GST activity of by these two plants in vivo maybe one of the reasons that make...

“…The Combretaceae family of plants has been widely used as traditional medicines [ 14 ]. Use of these plants to treat scorpion and snake bites, and mental problems and their use for the relief of sore throats and colds, fever, chest coughs associated with tuberculosis, pneumonia and venereal diseases like syphilis is common in most African communities [ 15 ]. Studies on the genus have shown presence of several phytochemical constituents including alkaloids, saponins, tannins and cardiac glycosides [ 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

Alkaloid extracts from Combretum zeyheri inhibit the growth of Mycobacterium smegmatis

Nyambuya

Mautsa

2017

BackgroundCurrent tuberculosis regimens have failed to combat the issue of drug resistance and ethno medicines may represent a possible source of antimycobacterial agents. Combretum species are well known in African traditional medicines and used for various ailments including pneumonia, venereal diseases like syphilis, mental problems, relief of sore throats and colds, fever, and chest coughs associated with tuberculosis. Alkaloids function as either hydrogen-acceptor or hydrogen-donor in hydrogen bonding critical for the interaction between targets thus, potentiating effects of curative agents on diseases. Alkaloid extracts from leaves of Combretum zeyheri, Combretum platypetalum, Combretum molle and Combretum apiculatum, were assessed for antimycobacterial activity to establish rationale for their use in traditional medicines for various ailments including pneumonia, relief of sore throats and colds, fever, and chest coughs associated with tuberculosis.MethodsAlkaloids were extracted from the leaves of Combretum zeyheri, Combretum platypetalum, Combretum molle and Combretum apiculatum. The broth microdilution method was used for the screening of growth inhibitory activity. The standard drug rifampicin was used as the positive control. Alkaloid extracts from the most potent plant species, Combretum zeyheri were further investigated for time-kill dependency effects on drug transport in Mycobacterium smegmatis.ResultsUsing the broth microdilution susceptibility method, C. zeyheri alkaloid extract, was found to have the most antimycobacterial effects with an MIC value of 125 μg/ml whilst MICs for C. molle and C. platypetalum were above 1000 μg/ml. An MBC value of 250 μg/ml was observed with alkaloid extracts from Combretum zeyheri whilst the remaining three Combretum species showed no bactericidal activity. It was also shown that C. zeyheri had potential efflux pump inhibitory activity. Determination of the time-kill kinetics of extracts from C. zeyheri showed not only a concentration-dependent activity but time-dependent bactericidal effect as well.ConclusionsAlkaloid extracts from the leaves of C. zeyheri have potential as a source of lead compounds that may be developed further into antimycobacterial compounds. The mechanism of action of may be due to inhibition of transport across the cell membrane. Further work needs to be done to isolate the active components in these extracts.