Hepatoprotective effects of leaf extract of Annona senegalensis against aflatoxin B1 toxicity in rats.

Global aflatoxin contamination of agricultural commodities is of the most concern in food safety and quality. This study investigated the hepatoprotective effect of 80% methanolic leaf extract of Annona senegalensis against aflatoxin B1 (AFB1)-induced toxicity in rats. A. senegalensis has shown to inhibit genotoxicity of aflatoxin B1 in vitro. The rats were divided into six groups including untreated control, aflatoxin B1 only (negative control); curcumin (positive control; 10 mg/kg); and three groups receiving different doses (100 mg/kg, 200 mg/kg, and 300 mg/kg) of A. senegalensis extract. The rats received treatment (with the exception of untreated group) for 7 days prior to intoxication with aflatoxin B1. Serum levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase, and creatinine were measured. Hepatic tissues were analysed for histological alterations. Administration of A. senegalensis extract demonstrated hepatoprotective effects against aflatoxin B1-induced toxicity in vivo by significantly reducing the level of serum aspartate aminotransferase and alanine aminotransferase and regenerating the hepatocytes. No significant changes were observed in the levels of alkaline phosphatase, lactate dehydrogenase, and creatinine for the AFB1 intoxicated group, curcumin+AFB1 and Annona senegalensis leaf extract (ASLE)+AFB1 (100 mg/kg, 200 mg/kg, and 300 mg/kg body weight [b.w.]) treated groups. Annona senegalensis is a good candidate for hepatoprotective agents and thus its use in traditional medicine may at least in part be justified.Contribution: The plant extract investigated in this study can be used in animal health to protect the organism from toxicity caused by mycotoxins.

HPLC-DAD-SPE-NMR isolation of tetracyclic spiro-alkaloids with antiplasmodial activity from the seeds of Erythrina latissima.

Seven tetracyclic spiro-alkaloids, i.e. glucoerysodine (1), erysodine (2), epi-erythratidine (3), erysovine (4), erythratidine (5), erysotrine (6) and erythraline (7) were isolated from the seeds of Erythrina latissima by means of conventional separation methods and HPLC-DAD-SPE-NMR. Their structures were elucidated by spectroscopic means. This is the first report on the isolation of compounds 3, 5 and 6 from this plant. Antiplasmodial activity against the chloroquine-resistant strain Plasmodium falciparum K1 and cytotoxicity against MRC-5 cells (human fetal lung fibroblast cells) was assessed in vitro. Erysodine (2) and erysovine (4) showed moderate activity (IC50 6.53 µM and 4.05 µM, respectively), compared with the standard chloroquine (IC50 = 0.14 µM). No cytotoxicity was observed in a concentration up to 64.0 µM.

In vitro antigenotoxic activity, in silico ADME prediction and protective effects against aflatoxin B1 induced hepatotoxicity in rats of an Erythrina latissima stem bark extract.

Stem bark of Erythrina latissima E. Mey (Leguminosae) contains a wide range of prenylated flavonoids able to counteract the genotoxic properties of aflatoxin B1 (AFB1). Thus, the hypothesis was raised that E. latissima stem bark extracts (ELBE) may counteract the in vivo hepatotoxic effects of aflatoxins, contaminants in food and feed. An HPLC-DAD method was developed and validated to determine the level of flavonoid aglycones (11.82%) and glycosides (16.17%). ADME, pharmacokinetic and drug-likeness assessment of major flavonoids of ELBE, using the web tool SwissADME, showed good oral bioavailability. The protective effect of ELBE against AFB1 induced genotoxicity in the Vitotox assay after metabolic activation was confirmed (IC50 of 44.32 µg/ml), followed by evaluation of its inhibitory effect on hepatotoxicity in rats induced by the same agent. Male Wistar rats were orally treated with ELBE (20 mg/kg, 50 mg/kg and 100 mg/kg) or curcumin (500 mg/kg) combined with piperine (20 mg/kg) - positive control, for 8 days prior to AFB1 exposure (1 mg/kg). The ELBE group showed a decreased activity of ALP and γ-GT compared to the AFB1 group. Histopathological examination of the liver demonstrated ameliorative effects of ELBE. Thus, ELBE could have a protective effect against hepatotoxins such as AFB1.

Antimutagenic constituents from Monanthotaxis caffra (Sond.) Verdc.

OBJECTIVES: Monanthotaxis caffra (Sond.) Verdc. (Annonaceae) has been reported to possess antitumoural properties. Preliminary screening showed that the crude methanolic leaf extract had strong antimutagenic effects against aflatoxin B1 -induced mutagenicity. The aim of this study was to isolate and evaluate the antimutagenic properties of the active constituents from M. caffra. METHODS: Different chromatographic, spectroscopic and spectrometric techniques were used for the isolation and identification of the antimutagenic constituents. The antimutagenic effect of the extract and compounds was evaluated using Ames, Vitotox and Comet assays. KEY FINDINGS: Bioassay-guided fractionation of the methanolic leaf extract yielded two antimutagenic compounds identified as (+)-crotepoxide and 5,6-diacetoxy1-benzoyloxymethyl-1,3-cyclohexadiene. Crotepoxide had strong antimutagenicity in the Vitotox assay with an IC50 value of 131 µg/ml. 5,6-Diacetoxy-1-benzoyloxymethyl-1,3-cyclohexadiene showed strong antimutagenic activity in the Ames assay with an IC50 value of 348.9 µg/plate and no antimutagenic activity in the Vitotox test. Furthermore, the compound was able to inhibit, block or prevent biotransformation of aflatoxin B1 by repressing the proteins involved in transcription. CONCLUSIONS: Crotepoxide and 5,6-diacetoxy-1-benzoyloxymethyl-1,3-cyclohexadiene have the potential to mitigate the risks arising from consumption of aflatoxin B1 -contaminated food and feed.

Isolation and characterization of the compounds responsible for the antimutagenic activity of Combretum microphyllum (Combretaceae) leaf extracts.

BACKGROUND: Mutations play a major role in the pathogenesis and development of several chronic degenerative diseases including cancer. It follows, therefore that antimutagenic compound may inhibit the pathological process resulting from exposure to mutagens. Investigation of the antimutagenic potential of traditional medicinal plants and compounds isolated from plant extracts provides one of the tools that can be used to identify compounds with potential cancer chemopreventive properties. The aim of this study was to isolate and characterise the compounds responsible for the antimutagenic activity of Combretum microphyllum. METHODS: The methanol leaf extract of C. microphyllum was evaluated for antimutagenicity in the Ames/microsome assay using Salmonella typhimurium TA98. TA100 and TA102. Solvent-solvent fractionation was used to partition the extracts and by using bioassay-guided fractionation, three compounds were isolated. The antimutagenic activity of the three compounds were determined in the Ames test using Salmonella typhimurium TA98, TA100 and TA102. The antioxidant activity of the three compounds were determined by the quantitative 2,2-diphenyl-1-picrylhydrazyl (DPPH)-free radical scavenging method. The cytotoxicity was determined in the MTT assay using human hepatocytes. RESULTS: A bioassay-guided fractionation of the crude extracts for antimutagenic activity led to the isolation of three compounds; n-tetracosanol, eicosanoic acid and arjunolic acid. Arjunolic acid was the most active in all three tested strains with a antimutagenicity of 42 ± 9.6%, 36 ± 1.5% and 44 ± 0.18% in S. typhimurium TA98, TA100 and TA102 respectively at the highest concentration (500 µg/ml) tested, followed by eicosanoic acid and n-tetracosanol. The antioxidant activity of the compounds were determined using the quantitative 2,2 diphenyl-1-picryhydrazyl (DPPH)-free radical scavenging method. Only arjunolic acid had pronounced antioxidant activity (measured as DPPH-free scavenging activity) with an EC50 value of 0.51 µg/ml. The cytotoxicity of the isolated compounds were determined in the MTT assay using human hepatocytes. The compounds had low cytotoxicity at the highest concentration tested with LC50 values >200 µg/ml for n-tetracosanol and eicosanoic acid and 106.39 µg/ml for arjunolic acid. CONCLUSIONS: Based on findings from this study, compounds in leaf extracts of C. microphyllum protected against 4-NQO and MMC induced mutations as evident in the Ames test. The antimutagenic activity of arjunolic acid may, at least in part, be attributed to its antioxidant activity resulting in the detoxification of reactive oxygen species produced during mutagenesis.

Antigenotoxic prenylated flavonoids from stem bark of Erythrina latissima.

A series of prenylated flavonoids was obtained from antigenotoxic extracts and fractions of stem bark of Erythrina latissima E. Mey (Leguminosae). In addition to five constituents never reported before, i.e. (2S)-5,7-dihydroxy-2-(4-hydroxy-2-(prop-1-en-2-yl)-2,3-dihydrobenzofuran-6-yl)chroman-4-one (erylatissin D), (2S)-5,7-dihydroxy-2-(4-methoxy-2-(prop-1-en-2-yl)-2,3-dihydrobenzofuran-6-yl)chroman-4-one (erylatissin E), 5,7-dihydroxy-3-(4-methoxy-2-(prop-1-en-2-yl)-2,3-dihydrobenzofuran-6-yl)-4H-chromen-4-one (erylatissin F), (2S)-5,7,8'-trihydroxy-2',2'-dimethyl-[2,6'-bichroman]-4-one (erylatissin G) and (2S)-5,7-dihydroxy-8'-methoxy-2',2'-dimethyl-[2,6'-bichroman]-4-one (dihydroabyssinin I), 18 known flavonoids were identified. Evaluation of the antigenotoxic properties (against genotoxicity induced by aflatoxin B1, metabolically activated) in the Vitotox assay revealed that most flavonoids were active. Sigmoidin A and B showed the highest activity, with an IC50 value of 18.7 µg/mL, equivalent to that of curcumin (IC50 18.4 µg/mL), used as a reference antigenotoxic compound.

The correlation between antimutagenic activity and total phenolic content of extracts of 31 plant species with high antioxidant activity.

BACKGROUND: Antimutagenic activity of plant extracts is important in the discovery of new, effective cancer preventing agents. There is increasing evidence that cancer and other mutation-related diseases can be prevented by intake of DNA protective agents. The identification of antimutagenic agents present in plants presents an effective strategy to inhibit pathogenic processes resulting from exposure to mutagenic and/or carcinogenic substances present in the environment. There are no reports on the antimutagenic activities of the plant species investigated in this study. Many mutations related to oxidative stress and DNA damage by reactive oxygen species (ROS) and reactive nitrogen species (RNS) have been identified in numerous human syndromes. Oxidative DNA damage plays a significant role in mutagenesis, cancer, aging and other human pathologies. Since oxidative DNA damage plays a role in the pathogenesis of several chronic degenerative diseases, the decrease of the oxidative stress could be the best possible strategy for prevention of these diseases. Antioxidant compounds can play a preventative role against mutation-related diseases, and thus have potential antimutagenic effects. METHODS: The number of antioxidant compounds present in methanol leaf extracts of 120 plant species was determined using a combination of Thin Layer Chromatography (TLC) and spraying with 2, 2-diphenyl-1-picrylhydrazyl (DPPH). The 31 most promising extracts were selected for further assays. The quantitative antioxidant activity was determined using DPPH free radical scavenging spectrophotometric assay. Total phenolic contents were determined using the Folin-Ciocalteu colorimetric assay. The mutagenicity of 31 selected extracts was determined in the Ames test using Salmonella typhimurium strains TA98 and TA100. The antimutagenicity of the plant extracts against 4-nitroquinoline 1-oxide (4-NQO) was also determined using the Ames test. RESULTS: Of the 120 plant extracts assayed qualitatively, 117 had some antioxidant activity. The selected 31 extracts contained well defined antioxidant compounds. These species had good DPPH free radical antioxidant activity with EC50 values ranging from 1.20 to 19.06 µg/ml. Some of the plant extracts had higher antioxidant activity than L-ascorbic acid (vitamin C). The total phenolic contents ranged from 5.17 to 18.65 mg GAE (gallic acid equivalent)/g plant extract). The total phenolic content of the plant extracts correlated well with the respective antioxidant activity of the plant extracts. No plant extract with good antioxidant activity had mutagenic activity. Several extracts had antimutagenic activity. The percentage inhibition of 4-NQO ranged from 0.8 to 77% in Salmonella typhimurium TA98 and from 0.8 to 99% in strain TA100. There was a direct correlation between the presence of antioxidant activity and antimutagenic activity of the plant extracts. Although no plant extract had mutagenic activity on its own, some of the plant extracts enhanced the mutagenicity of 4-NQO, a phenomenon referred to as comutagenicity. CONCLUSIONS: Some of the plant extracts investigated in this study had potential antimutagenic activities. The antimutagenic activities may be associated with the presence of antioxidant polyphenols in the extracts. From the results plant extracts were identified that were not mutagenic, not cytotoxic and that may be antimutagenic in the Ames test. For most plant extracts, at the highest concentration used (5 mg/ml), the level of antimutagenicity was below the recommended 45% to conclude whether plants have good antimutagenic activity. However, in most screening studies for antimutagenesis, a 20% decrease in the number of revertants must be obtained in order to score the extract as active. Psoralea pinnata L. had the highest percentage antimutagenicity recorded in this study (76.67 and 99.83% in S. typhimurium TA98 and TA100 respectively) at assayed concentration of 5 mg/ml. The results indicate that investigating antioxidant activity and the number of antioxidant compounds in plant extracts could be a viable option in searching for antimutagenic compounds in plants.

Polarity of extracts and fractions of four Combretum (Combretaceae) species used to treat infections and gastrointestinal disorders in southern African traditional medicine has a major effect on different relevant in vitro activities.

ETHNOPHARMACOLOGICAL IMPORTANCE: Gastrointestinal disorders and infections are the major pathoaetiologies of diarrhoea causing many problems in human health and animal production. Many Combretum species are used in traditional medicine to treat infectious diseases including diarrhoea and many other ailments by rural people in Africa and Asia. Much of the work done to date on this genus was on the non-polar or intermediate polarity components. Some parameters that may cause diarrhoea and the evaluation of more polar extracts have apparently not been investigated. AIMS: The polar components were extracted and fractionated by solvent-solvent fractionation to yield fractions with different polarities. The activity of these fractions on different parameters that could be involved in factors associated with diarrhoea was investigated. The cytotoxic activities of the extracts were also determined to evaluate the potential of these extracts to combat diarrhoea in production animals. MATERIALS AND METHODS: Phenolic-enriched leaf extracts of Combretum bracteosum (COB), Combretum padoides (COP), Combretum vendae (COV) and Combretum woodii (COW) were obtained by extracting with a mixture of 70% acetone acidified with 1% HCl and n-hexane. Acetone was removed from a portion of the 70% acetone extract and it was sequentially treated by solvent-solvent fractionation with dichloromethane, ethyl acetate, and butanol to yield fractions with a large variation in polarity. The phenolic constituents of the extracts and fractions were determined using standard procedures The antioxidant activities were determined using the 2,2-diphenyl-1-picrylhydrazyl (DPPH); 2,2'-azino-bis (3-ethylbenzothiazoline)-6-sulphonic acid (ABTS(+)) radical scavenging, ferric reducing antioxidant power (FRAP) methods and lipid peroxidation inhibitory capacity standard methods. The ferric reducing antioxidant activities of the fractions were also determined. The minimum inhibitory concentrations (MICs) of the crude extracts and fractions against four bacterial and three fungal strains were assessed with a microplate serial dilution method. Cyclooxygenase (COX) and lipoxygenase (LOX) enzyme inhibitory assays and cytotoxicity studies against Vero cells were also carried out. RESULT: Some of the fractions had much higher antioxidant activity than the positive controls. The average EC50 values of the extracts for the DPPH and ABTS antioxidant assays were 0.21-12µg/ml (COP), 0.25-16µg/ml (COV), 0.33-9.41µg/ml (COW) and 4.97-85µg/ml (COB) respectively while the mean EC50 values for the positive controls ascorbic acid and trolox were 1.28-1.51 and 1.02-1.19µg/ml respectively. All the crude extracts inhibited lipid peroxidation of linoleic acid by more than 80% at a concentration of 64 µg/ml. COP had the highest antibacterial activity with MICs ranging between 19-2500µg/ml, followed by COV with MICs ranging between 39-625µg/ml; COW and COB had similar MICs ranging between 39-2500µg/ml. COP also had the highest antifungal activity with MICs between 19-625µg/ml. The MIC for COW and COV ranged from 19 to 1250 µg/ml. COB had the lowest antifungal activity (MIC values were between 39 and 625 µg/ml). In general non-polar fractions had a high antimicrobial activity and polar fractions had a high antioxidant activity. The extracts had no activity against COX 1 and 2 enzymes in the anti-inflammatory assay but had good lipoxygenase inhibition. The crude extracts had high concentration of hydrolysable tannin (gallotannin). A good correlation (R(2)= 0.99) was found between the antioxidant activity and total tannin content indicating that, gallotannins may be responsible for the antioxidant activity. CONCLUSION: The results obtained in this study with more polar extracts indicate that the use of extracts of these plant species as antidiarrhoeal agents may have a scientific basis. The extractant used here extracted a much higher percentage of the phytochemicals than acetone. It was better for isolating antioxidant compounds (polar) but not good for isolating antimicrobial compounds (non-polar) from the same species compared to acetone, ethyl acetate, dichloromethane, and hexane.

Cytotoxicity of diplodiatoxin, dipmatol and diplonine, metabolites synthesized by Stenocarpella maydis.

The cytotoxicity of three Stenocarpella maydis metabolites (diplodiatoxin, dipmatol and diplonine) was investigated on Neuro-2a, CHO-K1 and MDBK cell lines. Diplodiatoxin was the most cytotoxic followed by dipmatol. Conversely, diplonine was not cytotoxic. Diplodiatoxin and dipmatol affected mitochondrial succinate dehydrogenase (MTT assay) and the overall viability of cells as assessed in real-time (xCELLigence assay). The results obtained so far indicate that diplodiatoxin and dipmatol exert their toxicity possibly via the necrotic cell death pathway.

In-vitro evaluation of selected Egyptian traditional herbal medicines for treatment of Alzheimer disease.

BACKGROUND: Egyptians recognized the healing power of herbs and used them in their medicinal formulations. Nowadays, "Attarin" drug shops and the public use mainly the Unani medicinal system for treatment of their health problems including improvement of memory and old age related diseases. Numerous medicinal plants have been described in old literature of Arabic traditional medicine for treatment of Alzheimer's disease (AD) (or to strengthen memory). METHODS: In this study, some of these plants were evaluated against three different preliminary bioassays related to AD to explore the possible way of their bio-interaction. Twenty three selected plants were extracted with methanol and screened in vitro against acetylcholinesterase (AChE) and cycloxygenase-1 (COX-1) enzymes. In addition, anti-oxidant activity using DPPH was determined. RESULTS: Of the tested plant extracts; Adhatoda vasica and Peganum harmala showed inhibitory effect on AChE at IC50 294 µg/ml and 68 µg/ml respectively. Moreover, A. vasica interacted reversibly with the enzyme while P. harmala showed irreversible inhibition. Ferula assafoetida (IC50 3.2 µg/ml), Syzygium aromaticum (34.9 µg/ml) and Zingiber officinalis (33.6 µg/ml) showed activity against COX-1 enzyme. Potent radical scavenging activity was demonstrated by three plant extracts Terminalia chebula (EC50 2.2 µg/ml), T. arjuna (3.1 µg/ml) and Emblica officinalis (6.3 µg/ml). CONCLUSION: Interestingly, differential results have been obtained which indicate the variability of the mode of actions for the selected plants. Additionally, the reversible interaction of A. vasica against AChE and the potent activity of F. assafoetida against COX-1 make them effective, new and promising agents for treatment of AD in the future, either as total extracts or their single bioactive constituents.

The antimicrobial, antioxidative, anti-inflammatory activity and cytotoxicity of different fractions of four South African Bauhinia species used traditionally to treat diarrhoea.

ETHNOPHARMACOLOGICAL IMPORTANCE: Many Bauhinia species, including those indigenous to South Africa, are used in traditional medicine across the world for treating ailments such as gastrointestinal tract (GIT) disorders, diabetes, infectious diseases and inflammation. AIMS: Several relevant aspects of different fractions of leaf extracts of Bauhinia bowkeri (BAB), Bauhinia galpinii (BAG), Bauhinia petersiana (BAP), and Bauhinia variegata (BAV) used in South African traditional medicine to alleviate diarrhoea related symptoms were evaluated. MATERIALS AND METHODS: The antioxidative activities of the extracts were determined using the 2, 2-diphenyl-1-picrylhydrazyl (DPPH), 2, 2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid (ABTS(+)) radical scavenging and ferric reducing antioxidant power (FRAP) methods. In vitro antimicrobial activities of the extracts were determined against bacterial strains (Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli and Enterococcus faecalis) and clinical isolates of the opportunistic fungal strains (Aspergillus fumigatus, Candida albicans, and Cryptococcus neoformans) using a serial dilution microplate method. The polyphenolic contents were quantified using standard methods, and anti-inflammatory activities of the crude extracts were determined using the cyclooxygenase and soybean 15-lipoxygenase enzyme inhibitory assays. The safety of the extracts was evaluated by determining the cytotoxicity against Vero cell lines. RESULTS: The acidified 70% acetone crude extract and their fractions had good antiradical potency against the DPPH and ABTS radicals. The methanol soluble portions of the butanol fractions were more potent (EC(50) ranges from 0.64 ± 0.05 to 1.51 ± 0.07 and 0.88 ± 0.18 to 1.49 ± 0.09 µg/ml against DPPH and ABTS radical respectively) compared to the standard, trolox and ascorbic acid (EC(50) ranges from 1.47 ± 0.24 to 1.70 ± 0.27 µg/ml) for both DPPH and ABTS. The crude extracts contained variable quantities of phenolic content. The crude extracts and their fractions had weak to good antimicrobial activities, inhibiting the growth of the organisms at concentrations ranging from 39 to 2500 µg/ml. The BAG crude extract and its fractions were the most active against the fungi (MICs ranging from 39 to 625 µg/ml) while the BAB extract and its fractions were the least active with the MICs ranging between 39 and 2500 µg/ml. Aspergillus fumigatus was the least susceptible fungus while Cryptococcus neoformans was the most susceptible. The phenolic-rich crude extracts of BAB, BAG, and BAP had moderate to good dose-dependent cyclooxygenase-1 enzyme inhibitory activity with inhibitions between 22.8% and 71.4%. The extracts were however, inactive against cyclooxygenase-2. The extracts had some level of cytotoxicity towards Vero cell lines, reducing cell viability to less than 10% at concentrations more than 50 µg/ml. CONCLUSION: The biological activities observed in Bauhinia species provide a scientific basis for the use of the plants in traditional medicines to treat diseases with multi-factorial pathogenesis such as diarrhoea, with each aspect of activity contributing to the ultimate therapeutic benefit of the plants. However, the use of the phenolic-rich extracts of these plants to treat diarrhoea or any other ailments in traditional medicine needs to be monitored closely because of potential toxic effects and selective inhibition of COX-1 with the associated GIT injury.

Ochnaflavone and ochnaflavone 7-O-methyl ether two antibacterial biflavonoids from Ochna pretoriensis (Ochnaceae).

The acetone extract of Ochna pretoriensis was evaluated for antibacterial activity using bioautography and serial microplate dilution methods against four nosocomial bacterial pathogens namely: Escherichia coli, Staphylococcus aureus, Enterococcus faecalis and Pseudomonas aeruginosa. A bioassay-guided fractionation of the crude extract led to the isolation of two antibacterial biflavonoids, ochnaflavone and ochnaflavone 7-O-methyl ether. Gram-negative bacteria were more sensitive to the isolated compounds than the Gram-positive bacteria (MIC values: 31.3 microg/mL for P. aeruginosa and 62.5 microg/mL for S. aureus). In addition, the isolated compounds were assessed for their potential toxic effects in the MTT toxicity assay using monkey kidney vero cells and Ames genotoxicity test using Salmonella typhimurium strain TA98. LC50 values were 125.9 microg/mL for ochnaflavone and 162.0/microg/mL for ochnaflavone 7-O-methyl ether. The isolated compounds have selectivity index values ranging from 1.29 to 4.03. Selectivity index values higher than one indicate that test samples are less toxic to the host cells than to the pathogens. The biflavonoids did not have any mutagenic effects in the Salmonella/microsome assay without metabolic activation.

Effect of cadmium accumulation on anti-inflammatory activity in two Eucomis species.

Eucomis species (Hyacinthaceae) are widely used in South Africa as traditional medicine. The bulbs are used to alleviate a variety of symptoms including pain and inflammation. High levels of cyclooxygenase-1 and -2 (COX-1 and COX-2) inhibitory activity have been associated with certain Eucomis species. The aim of this study was to quantify cadmium(Cd) accumulation and examine its effect on COX-1 and COX-2 anti-inflammatory activity in Eucomis autumnalis and Eucomis humilis. Cadmium application at 2 mg L(-1) over a 6 week period revealed a substantial difference in total Cd accumulation in E. autumnalis and E. humilis (40.2 and 15.3 mg Cd kg-1, respectively). When supplied with Cd at 2 mg L(-1), E. humilis bulbous extracts showed lower inhibitory activity than the control for both COX-1 and COX-2. E. autumnalis bulbous extracts had greater COX-1 activity compared to the control. While COX-2 activity was suppressed. Researchers should be aware of the effect of environmental contaminants when reporting on biological activity of crude plant extracts.

Inhibition of [3H]citalopram binding to the rat brain serotonin transporter by Amaryllidaceae alkaloids.

Twenty-one Amaryllidaceae alkaloids isolated from different Amaryllidaceae species were investigated for their affinity to the serotonin reuptake transport protein and for GABA(A)-benzodiazepine receptor binding. Cherylline (21), crinamine (7), crinine (1), epibuphanisine (2), epivittatine (6), maritidine (11), O-methylmaritidine (12), powelline (3), 1-O-acetyllycorine (18) and tazettine ( 13) showed affinity to the serotonin reuptake transport protein. Cherylline (21) and epivittatine (6) yielded the highest activity among the group. No GABA(A)-benzodiazepine receptor binding activity was exhibited by the alkaloids tested.

Anolignan B: a bioactive compound from the roots of Terminalia sericea.

Antibacterial bioassay-guided fractionation of an ethyl acetate root extract of Terminalia sericea led to the isolation of anolignan B. The isolated compound was further tested for anti-inflammatory activity using the cyclooxygenase enzyme assays (COX-1 and COX-2) and for potential mutagenic effects using the Ames test. In the antibacterial test, anolignan B showed activity against both Gram-positive and Gram-negative bacteria. The minimum inhibitory concentration values obtained (MIC) ranged from 3.8 microg/ml against Bacillus subtilis (Gram-positive) to 31 microg/ml against Escherichia coli (Gram-negative). In the anti-inflammatory assays, anolignan B showed activity against both COX-1 (IC(50) = 1.5 mM) and COX-2 (IC(50) = 7.5 mM) enzymes. No potential mutagenic effects were observed in the Salmonella microsome assay (TA98). Isolation of anolignan B from Terminalia sericea as well as the antibacterial and anti-inflammatory activities observed in this study has not been reported previously.

Anti-inflammatory activity and QSAR studies of compounds isolated from Hyacinthaceae species and Tachiadenus longiflorus Griseb. (Gentianaceae).

Twenty-two homoisoflavanones and structurally related compounds isolated from plants were screened for anti-inflammatory activity. Seventeen compounds were isolated from southern African Hyacinthaceae species, one from the Madagascan gentian Tachiadenus longiflorus Griseb. and four were of synthetic origin. Inhibition of prostaglandin synthesis in cell microsomal fractions was first evaluated, followed by screening for specific inhibition of isolated cyclooxygenase enzymes (COX-1 and COX-2). Six homoisoflavanone and structurally related compounds showed significantly high levels of anti-inflammatory activity in the microsomal fraction assay. Only one compound exhibited a high level of anti-inflammatory activity in the COX-1 enzyme assay and no significant activity was detected in the COX-2 enzyme assay. Biological screening was followed by a computer-based quantitative structure-activity relationship (QSAR) study. The physicochemical descriptors: strain energy, heat of formation, volume, surface area, aqueous phase energy, dipole moment, enthalpy, entropy, molar refractivity, parachor, density, refractive index, surface tension, polarizability, logP, Van der Waals interaction energy, Coulombic interaction energy and nonbonded interaction energy were used to characterize the structures of the homoisoflavanones and structurally related compounds. This study produced three equations with significant prediction values for the anti-inflammatory activity of the compounds investigated. The derived models also provided valuable parameter guidelines for those properties influencing the anti-inflammatory activity of the studied compounds.

Acetylcholinesterase enzyme inhibitory effects of amaryllidaceae alkaloids.

Twenty-three Amaryllidaceae alkaloids having several different ring types were evaluated for their acetylcholinesterase enzyme (AChE) inhibitory activity. The alkaloid 1- O-acetyllycorine (IC50 : 0.96 +/- 0.04) showed significant AChE inhibitory activity. In addition, crinine (IC50 : 461 +/- 14), crinamidine (IC50 : 300 +/- 27), epivittatine (IC50 : 239 +/- 9), 6-hydroxycrinamine (IC50 : 490 +/- 7), N-desmethyl-8alpha-ethoxypretazettine (IC50 : 234 +/- 13) N-desmethyl-8beta-ethoxypretazettine (IC50 : 419 +/- 8), lycorine (IC50 : 213 +/- 1), and 1,2-di- O-acetyllycorine (IC50 : 211 +/- 10) had weak activity. Lycorine-type alkaloids were the most active alkaloids with 1- O-acetyllycorine exhibiting inhibitory effects two-fold more potent than that of galanthamine.

Genotoxicity of melanoidin fractions derived from a standard glucose/glycine model.

Genotoxic compounds can act at various levels in the cell (causing gene, chromosome, or genome mutations), necessitating the use of a range of genotoxicity assays designed to detect these different types of mutations. The production of melanoidins during the processing and cooking of foods is associated with changes in their nutritional character, and the discovery of mutagenic substances in pyrolyzed protein and amino acids has raised concern about the safety of these foods. The aim of this work was to test melanoidin fractions in three different in vitro assays (Ames test, Vitotox test, and micronucleus test). These melanoidin fractions were produced from the condensation of glucose with glycine and their separation was conducted by dialysis. The crude reaction mixture (before dialysis) and both the LMW and HMW fractions obtained by dialysis showed no genotoxicity in these assays, despite being tested at concentrations much higher than those naturally found in food products. The LMW fraction, however, showed toxicity at these high concentrations. The volatile fraction produced in this reaction showed genotoxicity only in the Vitotox test, at high concentrations.

Investigating the safety of plants used in South African traditional medicine: testing for genotoxicity in the micronucleus and alkaline comet assays.

Previous studies indicate that traditional botanical remedies can be valuable for treating human disease. The potential risk from long-term use of such remedies has not, however, been fully investigated, especially in terms of their potential carcinogenic activity. In the present study, 51 South African plant species were selected on the basis of their use in traditional medicine and crude extracts were sequentially prepared from different dried plant parts using dichloromethane followed by 90% methanol. These extracts were tested for genotoxic activity in human peripheral blood lymphocytes using the micronucleus test, with further testing of select extracts using the alkaline comet assay. Screening results indicated the induction of significant numbers of micronuclei by many of the plant extracts. Several samples also induced DNA damage in human white blood cells using the alkaline comet assay. Although a number of these plants are recognised as toxic by traditional healers, several plants that are used in common remedies were found to be genotoxic and potentially dangerous. Environ.

Screening of medicinal plants used in South African traditional medicine for genotoxic effects.

Dichloromethane and 90% methanol extracts from 51 South African medicinal plants were evaluated for potential genotoxic effects using the bacterial Ames and VITOTOX tests with and without metabolic activation. Dichloromethane extracts from bulbs of Crinum macowanii showed mutagenicity in strain TA98 with and without metabolic activation, whereas extracts from leaves of Chaetacme aristata and foliage of Plumbago auriculata showed mutagenicity and/or toxicity. Extracts from the leaves of Catharanthus roseus and twigs of Combretum mkhzense were mutagenic with metabolic activation only. The only 90% methanol extracts that were mutagenic in strain TA98 were from the leaves of C. roseus and Ziziphus mucronata in the presence of metabolic activation. No genotoxic effects were found in strain TA100 or in the VITOTOX test.