Browsing by Author "Green, Ivan"

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    Cardiovascular effects of (13S)-9_, 13_- epoxylabda-6_(19), 15(14)diol dilactone, a diterpenoid isolated from the organic extract of leonotis leonurus leaves, in anaesthetized normotensive rats
    (2009) Chibuzo, Obikeze Kenechukwu; Mugabo, Pierre; Green, Ivan
    Plants used in traditional medicines have served as sources of some of the drug compounds used in medicines today, and could still serve as leads for then development of new drugs to treat existing chronic diseases such as hypertension. This study was aimed at the isolation and identification of a cardio-active compound from L. leonurus, a plant commonly used in traditional medicines in South Africa for the treatment of hypertension and other cardiac problems. The possible mechanisms by which the isolated compound produced its effect on the cardiovascular system were explored using the anaesthetized normotensive rat model.Fractionation of the organic extracts of the leaves led to the isolation of a novel diterpene,(13S)-9 , 13 -epoxylabda-6 (19),15(14)diol dilactone (EDD) whose structure was elucidated using infra red (IR), nuclear magnetic resonance (NMR), mass spectroscopy(MS), and X-ray diffraction analysis. In anaesthetized normotensive male Wistar rats, EDD(0.5 mg/kg – 5.0 mg/kg; IV) produced slight non-significant decreases in systolic pressure(SP), diastolic pressure (DP), and mean arterial pressure (MAP) with the lower (0.5 mg/kg– 2.0 mg/kg) doses, while significant increases in SP, DP and MAP occurred with the higher (3.0 mg/kg – 5.0 mg/kg) doses. All doses of EDD administered also produced significant decreases in heart rate (HR).Prazosin and reserpine pre-treatment abolished the vasoconstrictive effect of EDD,suggesting an indirect vasoconstrictive effect for EDD via the release of catecholamines.Atenolol pre-treatment led to increases in the negative chronotropic effect of EDD, while the positive chronotropic effect of dobutamine was significantly decreased by EDD,suggesting the involvement of the 1 adrenoceptor in the negative chronotropic effect of EDD. In animals pre-treated with verapamil, a cardio-selective Ca2+ channel blocker, no significant changes in HR occurred with all EDD doses, but HR values were significantly lower than those obtained with EDD in non pre-treated animals.The results of this study indicate that (13S)-9 , 13 -epoxylabda-6 (19),15(14)diol dilactone, a novel dilactone diterpene isolated from the leaves of L. leonurus has an effect on the cardiovascular system. EDD exhibits a dual effect on the cardiovascular system by producing a vasoconstrictive effect accompanied by bradycardia. The vasoconstrictive effect of EDD is probably due to the release of catecholamines, while the negative chronotropic effect is probably due to 1 adrenoceptor antagonism. Further studies are however required to fully determine the mechanism by which EDD produces its cardiovascular effects.
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    Cardiovascular effects of Leonotis leonurus extracts in normotensive rats and in isolated perfused rat heart
    (University of the Western Cape, 2004) Obikeze, Kenechukwu; Dietrich, Danielle; Green, Ivan; Burger, Andreas; School of Pharmacy; Faculty of Science
    This thesis discussed the cardiovascular effects of the aqueous leaf extract and a fraction of the methanol extract of Leonotis leonurus, a plant commonly used in traditional medicine in South Africa for the treatment of hypertension and other cardiac problems. The cardiovascular effects was tested on anaesthetized normotensive male Wistar rats and isolated perfused rat hearts.
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    Cardiovascular effects of the alkaloid hippadine on the isolated perfused rat heart
    (Open Access Science Research Publisher, 2012) Mugabo, Pierre; Obikeze, Kenechukwu; Njagi, Angela; Burger, Andries; Dietrich, Danielle; Green, Ivan
    Crinum macowanii has been used extensively in traditional medicines for treatment of various illnesses such as oedema and ‘heart disease’. Previous studies of the crude bulb extracts on Langendorff perfused isolated rat hearts indicated a positive inotropic effect. The aim of this study was to isolate and characterize compound(s) from C. macowanii with cardiovascular effects similar to that observed with the crude extracts of the plant. The methanol extract of dried bulbs was extracted for alkaloids, and structural elucidation of the isolated alkaloid identified it as hippadine. The cardiovascular effects of hippadine was evaluated in vitro in isolated perfused rat hearts using the “double sided” working heart system. Perfusion with 0.5 μg/ml and 5.0 μg/ml hippadine in Krebs-Hanseleit buffer led to significant decreases in coronary flow, aortic output, cardiac output, systolic pressure, and heart rate, accompanied by increases in diastolic pressure. Hippadine exhibited a negative chronotropic and inotropic effect on the isolated rat heart and is responsible either partly or fully for the cardiovascular effects of C. macowanii.
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    Characterization and Cradiovascular Effects of (13S)-9α,13α-epoxylabda-6β(19),15(14)diol dilactone, a Diterpenoid Isolated from Leonotis leonurus
    (South African Chemical Institute, 2008) Obikezea, Kene C.; McKenzieb, Jean M.; Green, Ivan; Mugabo, Pierre
    A new diterpenoid, (13S)-9 ,13 -epoxylabda-6 (19),15(14)diol dilactone (1), was isolated from Leonotis leonurus and the structure determined via NMR analysis. The compound causes significant changes in blood pressure of anaesthetized normotensive rats and exhibits a negative chronotropic effect.
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    Development of novel hypervalent iodine conjugation strategies towards pneumococcal conjugate vaccines
    (2013) Fumbatha, Sinethemba; Green, Ivan; Mohamed, Ebrahim
    Invasive pneumococcal disease (IPD), which includes potentially fatal conditions such as meningitis, septicaemia and pneumonia poses a threat in children aged <5 years, pneumonia being the leading cause of child mortality worldwide. Even though capsular polysaccharides are the main antigens involved in the immunity to encapsulated bacteria, it was found that in children in that age group, the immune system was unresponsive. Conjugate vaccines however induce immunologic memory and provide long-term protective immunity. Therefore the aim of this project was to develop novel conjugation strategies towards a pneumococcal conjugate vaccines and focuses mainly on the serotypes that are a burden to the African continent. The chemistry involved in developing a conjugate vaccine is of importance beacuse while some polysaccharides contain chemical grouping which can be conveniently utilized for conjugation, many medically important ones require derivatization before they can be coupled to protein. Derivatization of which can be achieved through various strategies, important to note is through hypervalent iodine oxidants. Two hypervalent iodine reagents, O-Methyl substituted-1-hydroxy-1,2-benziodoxol-3(1H)-one 1-oxide (Me-IBX)and modified 1-hydroxy-1,2-benziodoxol-3(1H)-one 1-oxide (mIBX)were successfully synthesized in preparation for the use in polysaccharide, polyribitol phosphate, (PRP) oxidation. The polysaccharide to be oxidised was first size reduced by microfluidisation to allow maximum oxidation. However, the extent to which oxidisation was achieved was not enough to conjugate the polysaccharide to the protein of preference, Bovine Serum Albumin, (BSA).
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    Importance and relevance of phytochemicals present in Galenia Africana
    (Hindawi, 2022) Heredia, Dario; Green, Ivan; Klaasen, Jeremy
    Many people in developing countries rely primarily on medicinal plants as their main source of healthcare, particularly for the treatment of skin infections. Despite the widespread use of medicinal plants, there is a lack of literature describing the relevance and risks of exposure of the phytochemicals present. Galenia africana has been used traditionally in the form of pastes, decoctions, and lotions to treat wounds and other skin-related ailments. -is is a report on the phytochemical composition of G. africana and a review on the pharmacological importance and relevance of these phytochemicals. -e major groups of phytochemicals identified in G. africana extracts were aliphatics, aliphatic triterpenoids, fatty acids, flavonoids, and phenolic and tocopherol compounds. -ese have been found to exhibit medicinal properties, thus highlighting the need to assess the safety of G. africana for topical application. -e information related to the safety of the various compounds could indicate the potential risks related to accidental intake of the extract upon topical product applications. -is report concludes that the quantities of the phytochemicals present in G. africana should not cause undue risk to human health, which provides comfort to pursue future work on using and developing G. africana as a therapeutic agent.
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    Inorganic ions in leonotis leonurus extract do not explain changes in isolated Wistar rat heart function
    (Open Access Science Research Publisher, 2011) Burger, Andries; Mugabo, Pierre; Henkel, Ralf; Green, Ivan
    Leonotis leonurus (L. leonurus) R. Br (Lamiaceae) is used by healers in South Africa. The present study was conducted to determine if the L. leonurus effect on isolated rat heart is due to ionic changes in the perfusion fluid.
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    Phytochemical screening and biological activity studies of five South African indigenous medicinal plants
    (Academic Journals, 2010) Babajide, Jelili Olalekan; Mabusela, Wilfred T.; Green, Ivan; Ameer, Farouk; Weitz, Frans; Iwuoha, Emmanuel I.
    Different extracts and fractions of five selected indigenous South African medicinal plants, namely, Cissampelos capensis, Geranium incanum and three Gethyllis species, were subjected to phytochemical screening and testing for cytotoxicity using the brine shrimp lethality bioassay, and antimicrobial activity assays against nine microbes, which included three fungal species, three Gram negative and three Gram positive bacteria.The majority of the extracts tested positive for the presence of tannins, phenolics and flavonoids, while in selected cases, phytochemical tests suggested the presence of essential oils, glycosides or alkaloids. The methanol extract of Gethyllis gregoriana displayed the highest cytotoxicity levels. Generally, the highest levels of biological activity were shown to reside in the methanolic extracts, while hexane extracts revealed very low to zero activity. The total tertiary alkaloid (TTA) of C. capensis was mostly active against Bacillus subtilis, a Gram +ve bacteria. The trends observed for the cytotoxicity assay were in agreement with those observed for the antimicrobial assay.
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    Pt-Sn/C as a possible methanol-tolerant cathode catalyst for DMFC
    (Springer Verlag, 2013) Martin, Lynwill G.; Green, Ivan; Wang, X.; Pasupathi, Sivakumar; Pollet, Bruno G.
    An effective method was developed for preparing highly dispersed nano-sized Pt–Sn/C electrocatalyst synthesised by a modified polyol reduction method. From XRD patterns, the Pt–Sn/C peaks shifted slightly to lower 2θ angles when compared with commercial Pt/C catalyst, suggesting that Sn formed alloy with Pt. Based on HR-TEM images, the Pt–Sn/C nanoparticles showed small particle sizes and well dispersed onto the carbon support with a narrow particle distribution. The methanol oxidation reaction on the as-prepared Pt–Sn/C catalyst appeared at lower currents (+7.08 mA at +480 mV vs. Ag/AgCl) compared to the commercial Pt/C (+8.25 mA at +480 mV vs. Ag/AgCl) suggesting that the Pt–Sn/C catalyst has ‘methanol tolerance capabilities’. Pt–Sn/C HA Slurry pH3 catalysts showed better activity towards the oxygen-reduction reaction (ORR) than commercial Pt/C which could be attributed to smaller particle sizes. In our study, the Pt–Sn/C catalyst appears to be a promising methanol-tolerant catalyst with activity towards the ORR in the DMFC.
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    Some alkaloids and flavonoids from Cissampelos capensis
    (Academic Journals, 2015) Babajide, Jelili Olalekan; Mabusela, Wilfred T.; Green, Ivan
    Following the screening of several plant species from an inventory of common medicinal plants from South Africa for medicinal properties, Cissampelos capensis was selected for further investigation due to its interesting and useful ethnomedicinal properties. This study attempts to relate specific constituents present in this plant with its widespread ethnomedicinal uses. Six compounds were isolated and their structures were unambiguously established by spectroscopic methods. The compounds are: 5,6-dehydro-4,5-dihydroxy-1,3,6-trimethoxy-17-methylmorphinan-7-one (1); 1,2-methylenedioxy-3-hydroxy -9,10-dimethoxyaporphine (2); 5,6-didehydro-4-hydroxy-3,6-dimethoxy-17-methylmorphinan-7-one (3); 3,7,8,3'-tetramethoxy- 6 - C-methyl- 5,4'-dihydroxyflavone (6 -C-methylquercetin 3, 3',7, 8 -tetramethyl ether) (4); 5, 7, 8 -trihydroxy-2?, 5?-dimethoxy-3?,4?- methylenedioxyisoflavanone (5); 3 -methoxy-6 -C-methyl-3',4',5,7,8 -pentahydroxyflavone (6 -C- methylquercetin -3-methyl ether) (6). Five of the isolated compounds, (viz., 1,2,4,5 and 6) have, to our knowledge, not been reported previously. The crude fractions and isolates were tested for cytotoxicity using the brine shrimp lethality test and for antimicrobial properties using nine microbes, including three Gram -ve, three Gram +ve bacteria and three fungi. The Gram-negative bacteria were Pseudomonas aeruginosa (NCTC 10332), Proteus vulgaris (NCTC 4175) and Escherichia coli Sero type 1 (NCTC 09001), while the Gram-positive bacteria were Bacillus subtilis (NCTC 8236), Staphylococcus aureus (NCTC 13134) and Bacillus licheniformis (NCTC 01097). The Fungal species used were Candida albicans (ATCC 90028), Candida eropiralis (ATCC 750) and Aspergillus niger (ATCC 10578). The n-Hex fractions were not active while the highest activities were found in the methanolic extracts. The total tertiary alkaloid fraction (TTA) showed the highest activity against the Bacillus substillis. Compounds 1, 2 and 5 appear to be the most promising with regards to the prospects of drug development.
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    The synthesis and electrochemical studies of chalcones and flavanones: an investigation of their antioxidant activity
    (University of Western Cape, 2013) Baugaard, Carlo; Green, Ivan; Jahed, Nazeem
    Flavonoids, one of the biggest classes of secondary metabolites, are found abundantly in nature in a broad range of fruits, vegetables and beverages such as tea, coffee, beer, wine and fruit drinks. Flavonoids have been reported to exert multiple biological functions as well as tremendous pharmacological activity, including anticancer activity, protection, antioxidant activity, cardiovascular protection, antibacterial, antifungal and antiviral activity. The antioxidant activity of flavones is reported to be associated with those bearing hydroxyl functions. In the present study, several reaction steps have been carried out to synthesize three sub classes of flavonoids namely; chalcones, dihydrochalcones and flavanones with various substituents attached. The first step involved protection of hydroxyl groups of acetophenone and benaldehyde as starting materials. Thereafter the Clasien Schmidt condensation reaction, under basic conditions, was performed to afford chalcone intermediates. Treatment of these chalcones with sodium acetate, under reflux, afforded flavanones as a single product in high yields. Thereafter all protecting groups where removed to yield the final products. All products and intermediates where purified by column chromatography and were characterized by Nuclear Magnetic Resonance Spectroscopy (NMR) (1H NMR and 13C NMR). An electrochemical analysis on all flavonoid compounds was performed by Cyclic Voltammetry (CV) and Square Wave Voltammetry (SWV) to give information on the accessible redox couples identified by their oxidation potentials. Oxidation potentials, which gave valuable information about reducing ability and hence the antioxidant activity, where used to compare all compounds. The antioxidant activity was observed to increase with the addition of hydroxyl groups on the B-ring. Compounds with a combination of hydroxyl groups on the A-ring and methoxy groups on the B-ring showed increased antioxidant activity when compared to those with only hydroxyl groups on the base structure. 2, 5, 4’-trihydroxy dihydrochalcone showed moderate antioxidant ability. However the 2, 5, 4’-trihydroxychalcone, containing the α, β unsaturated double bond, proved to have the greatest antioxidant ability.