In vitro drug-herb interaction potential of African medicinal plant products used by Type II diabetics
- Authors: Fang, Yuan Yuan
- Date: 2011
- Subjects: Materia medica, Vegetable -- South Africa , Drugs -- Therapeutic use , Drug-herb interactions -- South Africa , Non-insulin-dependent diabetes -- South Africa , Non-insulin-dependent diabetes -- Treatment -- South Africa
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:10317 , http://hdl.handle.net/10948/1341 , Materia medica, Vegetable -- South Africa , Drugs -- Therapeutic use , Drug-herb interactions -- South Africa , Non-insulin-dependent diabetes -- South Africa , Non-insulin-dependent diabetes -- Treatment -- South Africa
- Description: In Africa, use of medicinal plants for the treatment of diabetes is very common. However, efficacy on co-administering of medicinal plants with therapeutic drugs hasn't been fully determined, especially for African medicinal plants. The current study focused on assessing the in vitro modulation effects of three popular African medicinal plants, namely: Aloe ferox, Sutherlandia frutescens and Prunus africana (including five commercial preparations containing these medicinal plants) on two of the most important anti-diabetic drug metabolising enzymes, Cytochrome P450 (CYP450) 2C9 and CYP3A4 and a key drug efflux transporter, P-glycoprotein (P-gp). Vivid® microsome-based screening kits were used to assess inhibitory potency of plants preparations on CYP2C9 and CYP3A4 enzymes activities. The study showed that P. africana was a more potent inhibitor of CYP2C9 and CYP3A4 activity than the corresponding positive controls Ginkgo biloba and St. John's wort, which are known to cause clinically significant drug-herb interactions. S. frutescens leaf extract demonstrated potent to moderate inhibition on both the tested CYP activities, while its commercial products (Promune® and Probetix®) possessed moderate to mild inhibitory effects on the activities of both CYPs. Potent inhibitory effect on CYP2C9 and CYP3A4 was seen with Aloe Ferox®. Prosit® and Aloes powder® showed potent to moderate inhibition on CYP2C9 activity and moderate to mild inhibition on CYP3A4 activity. In addition to CYP450 activity, the present study also investigated the effects of the selected medicinal plant products on the activity of the main drug efflux protein, P-gp. A screening assay was specifically developed to assess the potential for herbal remedies to interact with P-gp mediated drug absorption. The assay is based on the principle of the reversal of drug resistance in modified Caco-2 cells specifically altered to express high iv efflux protein activity. These cells display a multidrug resistance phenotype and the addition of a plant extract containing a P-gp inhibitor or substrate will inhibit or compete with any cytotoxic drug and consequently reverse the drug resistance. The suitability of the assay was confirmed using a known P-gp inhibitor. The study observed that the anti-proliferation effect of vinblastine was significantly enhanced in vinblastine-resistant Caco-2 cells, which have high P-gp expression, when they were exposed to the selected African herbal preparations. This observation indicates that the studied plant preparations may alter P-gp functionality and therefore lead to interference with the absorption of co-administered drugs. The outcomes of this study provide useful information on whether there are any potential drug-herb interactions between the commonly used African medicinal plants and oral anti-diabetic drugs, at the level of CYP and P-gp drug metabolism and could contribute to better therapeutic management of Type II diabetics. However these predicted interactions will need to be verified in a clinical setting.
- Full Text:
- Date Issued: 2011
- Authors: Fang, Yuan Yuan
- Date: 2011
- Subjects: Materia medica, Vegetable -- South Africa , Drugs -- Therapeutic use , Drug-herb interactions -- South Africa , Non-insulin-dependent diabetes -- South Africa , Non-insulin-dependent diabetes -- Treatment -- South Africa
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:10317 , http://hdl.handle.net/10948/1341 , Materia medica, Vegetable -- South Africa , Drugs -- Therapeutic use , Drug-herb interactions -- South Africa , Non-insulin-dependent diabetes -- South Africa , Non-insulin-dependent diabetes -- Treatment -- South Africa
- Description: In Africa, use of medicinal plants for the treatment of diabetes is very common. However, efficacy on co-administering of medicinal plants with therapeutic drugs hasn't been fully determined, especially for African medicinal plants. The current study focused on assessing the in vitro modulation effects of three popular African medicinal plants, namely: Aloe ferox, Sutherlandia frutescens and Prunus africana (including five commercial preparations containing these medicinal plants) on two of the most important anti-diabetic drug metabolising enzymes, Cytochrome P450 (CYP450) 2C9 and CYP3A4 and a key drug efflux transporter, P-glycoprotein (P-gp). Vivid® microsome-based screening kits were used to assess inhibitory potency of plants preparations on CYP2C9 and CYP3A4 enzymes activities. The study showed that P. africana was a more potent inhibitor of CYP2C9 and CYP3A4 activity than the corresponding positive controls Ginkgo biloba and St. John's wort, which are known to cause clinically significant drug-herb interactions. S. frutescens leaf extract demonstrated potent to moderate inhibition on both the tested CYP activities, while its commercial products (Promune® and Probetix®) possessed moderate to mild inhibitory effects on the activities of both CYPs. Potent inhibitory effect on CYP2C9 and CYP3A4 was seen with Aloe Ferox®. Prosit® and Aloes powder® showed potent to moderate inhibition on CYP2C9 activity and moderate to mild inhibition on CYP3A4 activity. In addition to CYP450 activity, the present study also investigated the effects of the selected medicinal plant products on the activity of the main drug efflux protein, P-gp. A screening assay was specifically developed to assess the potential for herbal remedies to interact with P-gp mediated drug absorption. The assay is based on the principle of the reversal of drug resistance in modified Caco-2 cells specifically altered to express high iv efflux protein activity. These cells display a multidrug resistance phenotype and the addition of a plant extract containing a P-gp inhibitor or substrate will inhibit or compete with any cytotoxic drug and consequently reverse the drug resistance. The suitability of the assay was confirmed using a known P-gp inhibitor. The study observed that the anti-proliferation effect of vinblastine was significantly enhanced in vinblastine-resistant Caco-2 cells, which have high P-gp expression, when they were exposed to the selected African herbal preparations. This observation indicates that the studied plant preparations may alter P-gp functionality and therefore lead to interference with the absorption of co-administered drugs. The outcomes of this study provide useful information on whether there are any potential drug-herb interactions between the commonly used African medicinal plants and oral anti-diabetic drugs, at the level of CYP and P-gp drug metabolism and could contribute to better therapeutic management of Type II diabetics. However these predicted interactions will need to be verified in a clinical setting.
- Full Text:
- Date Issued: 2011
Antimicrobial activity of selected Eastern Cape medical plants
- Authors: Mohlakoana, Keneuoe
- Date: 2010
- Subjects: Materia medica, Vegetable -- South Africa , Drug resistance in microorganisms -- South Africa , Anti-infective agents -- South Africa , Antibiotics
- Language: English
- Type: Thesis , Masters , MTech
- Identifier: vital:10120 , http://hdl.handle.net/10948/1199 , Materia medica, Vegetable -- South Africa , Drug resistance in microorganisms -- South Africa , Anti-infective agents -- South Africa , Antibiotics
- Description: Bacterial resistance to antibiotics has been a great problem for many years. The degree of resistance and the speed with which resistance develops varies with different organisms and different drugs. Enzymes called β-lactamases are produced by bacteria and are one mechanism in which bacteria develop antimicrobial resistance. Gram-negative bacteria producing enzymes called ESBLs because of their wide substrate range are of a particular concern in nosocomial infections. In many countries people still use traditional medicine derived from plants as an alternative to the Western medicine due to increased cost of Western medicine and microbial resistance of antibiotic treatments. Biologically active compounds isolated from plants species are used in herbal medicine. Because of the high prevalence of the ESBLs and their increasing resistance to the antibiotics, this research study was done to test the antimicrobial activities of selected medicinal plants of the Eastern Cape; G. incanum, D. angustifolia and E. autumnalis which were traditionally used to treat various infections. The in vitro antimicrobial activity of three different extracts (acetone, methanol & distilled water) and the traditional preparations of the three plants were tested against the selected strains of ESBL-producing bacteria, non β-lactamase producers and the different fungal species. The extracts were screened against 26 Gram-positive bacterial strains, 53 Gram-negative bacterial strains and 15 fungal strains. The Gram-positive bacteria included strains from S. aureus, B. cereus and E. faecalis. The Gram-negative bacteria included strains from E. ii coli, E. cloacae, K. pneumoniae, P. aeruginosa and Acinetobacter spp. The fungal strains included 9 strains of Candida albicans and a single strain of each of the following opportunistic fungi, Mucor sp, Geotrichium sp, Penicillium sp, Fusarium sp and Rhizopus sp. The agar dilution assay was used for the antimicrobial screening of the plants extracts and for the determination of the MICs. The Ames test was performed for the determination of probable carcinogenicity of the extracts of G. incanum and D. angustifolia. The distilled water extracts followed by acetone extracts of the plants revealed the highest antimicrobial activity against the different microbial strains. The extracts of G. incanum followed by the extracts of D. angustifolia inhibited the highest number of microbial strains. The extracts of E. autumnalis did not show any antimicrobial activity against all the pathogens in this study. More of the Gram-positive bacteria were inhibited by the plant extracts. The lowest MIC was obtained with Gram-positive bacteria. The bacterial strains of E. faecalis and P. aeruginosa were not inhibited by any of the plants extracts in the agar dilution assay yet Acinetobacter species which are MDR were inhibited by the distilled water and methanol extracts of G. incanum. A single strain of Mucor sp was the only spore forming fungi that was inhibited by the distilled water extracts of G. incanum. None of the plants extracts showed any mutagenic effects on the TA100 S. typhimurium strains incorporated on the Ames test. Apart from revealing of new antimicrobial agents that may be used against resistant organisms, the proper use of antimicrobial agents should be recommended. The study has highlighted a need for further investigations on the properties of the medicinal plants used in this study.
- Full Text:
- Date Issued: 2010
- Authors: Mohlakoana, Keneuoe
- Date: 2010
- Subjects: Materia medica, Vegetable -- South Africa , Drug resistance in microorganisms -- South Africa , Anti-infective agents -- South Africa , Antibiotics
- Language: English
- Type: Thesis , Masters , MTech
- Identifier: vital:10120 , http://hdl.handle.net/10948/1199 , Materia medica, Vegetable -- South Africa , Drug resistance in microorganisms -- South Africa , Anti-infective agents -- South Africa , Antibiotics
- Description: Bacterial resistance to antibiotics has been a great problem for many years. The degree of resistance and the speed with which resistance develops varies with different organisms and different drugs. Enzymes called β-lactamases are produced by bacteria and are one mechanism in which bacteria develop antimicrobial resistance. Gram-negative bacteria producing enzymes called ESBLs because of their wide substrate range are of a particular concern in nosocomial infections. In many countries people still use traditional medicine derived from plants as an alternative to the Western medicine due to increased cost of Western medicine and microbial resistance of antibiotic treatments. Biologically active compounds isolated from plants species are used in herbal medicine. Because of the high prevalence of the ESBLs and their increasing resistance to the antibiotics, this research study was done to test the antimicrobial activities of selected medicinal plants of the Eastern Cape; G. incanum, D. angustifolia and E. autumnalis which were traditionally used to treat various infections. The in vitro antimicrobial activity of three different extracts (acetone, methanol & distilled water) and the traditional preparations of the three plants were tested against the selected strains of ESBL-producing bacteria, non β-lactamase producers and the different fungal species. The extracts were screened against 26 Gram-positive bacterial strains, 53 Gram-negative bacterial strains and 15 fungal strains. The Gram-positive bacteria included strains from S. aureus, B. cereus and E. faecalis. The Gram-negative bacteria included strains from E. ii coli, E. cloacae, K. pneumoniae, P. aeruginosa and Acinetobacter spp. The fungal strains included 9 strains of Candida albicans and a single strain of each of the following opportunistic fungi, Mucor sp, Geotrichium sp, Penicillium sp, Fusarium sp and Rhizopus sp. The agar dilution assay was used for the antimicrobial screening of the plants extracts and for the determination of the MICs. The Ames test was performed for the determination of probable carcinogenicity of the extracts of G. incanum and D. angustifolia. The distilled water extracts followed by acetone extracts of the plants revealed the highest antimicrobial activity against the different microbial strains. The extracts of G. incanum followed by the extracts of D. angustifolia inhibited the highest number of microbial strains. The extracts of E. autumnalis did not show any antimicrobial activity against all the pathogens in this study. More of the Gram-positive bacteria were inhibited by the plant extracts. The lowest MIC was obtained with Gram-positive bacteria. The bacterial strains of E. faecalis and P. aeruginosa were not inhibited by any of the plants extracts in the agar dilution assay yet Acinetobacter species which are MDR were inhibited by the distilled water and methanol extracts of G. incanum. A single strain of Mucor sp was the only spore forming fungi that was inhibited by the distilled water extracts of G. incanum. None of the plants extracts showed any mutagenic effects on the TA100 S. typhimurium strains incorporated on the Ames test. Apart from revealing of new antimicrobial agents that may be used against resistant organisms, the proper use of antimicrobial agents should be recommended. The study has highlighted a need for further investigations on the properties of the medicinal plants used in this study.
- Full Text:
- Date Issued: 2010
Leonotis leonurus: the anticoagulant and antidiabetic activity of Leonotis leonurus
- Authors: Mnonopi, Nandipha
- Date: 2010
- Subjects: Medicinal plants -- South Africa , Materia medica, Vegetable -- South Africa , Diabetes -- Alternative treatment -- South Africa , Plant bioactive compounds , Leonotis leonurus -- Physiological aspects
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:10323 , http://hdl.handle.net/10948/1194 , Medicinal plants -- South Africa , Materia medica, Vegetable -- South Africa , Diabetes -- Alternative treatment -- South Africa , Plant bioactive compounds , Leonotis leonurus -- Physiological aspects
- Description: Commercial marrubiin, aqueous and organic extracts of Leonotis leonurus were tested in vitro for their anticoagulant and antiplatelet activities. The aqueous extract inhibited platelet aggregation by 69.5 percent (100 μg/mL), while the organic extract (100 μg/mL) and marrubiin (5 μg/mL) showed 92.5 percent and 91.6 percent inhibition, respectively, by inhibiting the binding of fibrinogen to glycoprotein IIb/IIIa receptor in a concentration dependent manner. The extracts significantly prolonged activated partial thromboplastin time compared to untreated plasma controls. Fibrin and D-Dimer formation were drastically decreased. The extracts and marrubiin concentration-dependently inhibited calcium mobilization induced by collagen and thrombin. The formation of thromboxane A2 was also significantly reduced by both the extracts and marrubiin. Protein secretion and platelet adhesion were significantly reduced by both the extracts and marrubiin. The organic extract and marrubiin showed a more pronounced effect than the aqueous extracts in all the in vitro assays. The ex-vivo animal model confirmed the results obtained in vitro. Similar to the in vitro studies, activated partial thromboplastin time clotting time was prolonged by marrubiin and the number of aggregated platelets were significantly reduced relative to aspirin. The findings reflect that marrubiin largely contributes to the organic extract's anticoagulant and antiplatelet effect in vitro. INS-1 cells were cultured under normo- and hyperglycaemic conditions. Marrubiin and the two Leonotis leonurus extracts were screened for anti-diabetic activity in vitro. The stimulatory index of INS-1 cells cultured under hyperglycaemic conditions was significantly increased by 60 percent and 61 percent (p<0.01; n=5) in cells exposed to the organic extract (10 μg/mL) and marrubiin (500 ng/mL), respectively, relative to the normoglycaemic conditions. The gene expression of insulin was significantly increased by 76.5 and 71 percent, and of glucose transporter-2 by 93 and 92.5 percent for marrubiin and the organic extract, respectively, under the same conditions stipulated above (p<0.01; n=4). The extract and marrubiin similarly showed an increase in respiratory rate under hyperglycaemic conditions. Marrubiin increased insulin secretion, HDL-cholesterol, while it decreased total cholesterol, LDL-cholesterol and the atherogenic index in the in vivo rat model.
- Full Text:
- Date Issued: 2010
- Authors: Mnonopi, Nandipha
- Date: 2010
- Subjects: Medicinal plants -- South Africa , Materia medica, Vegetable -- South Africa , Diabetes -- Alternative treatment -- South Africa , Plant bioactive compounds , Leonotis leonurus -- Physiological aspects
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:10323 , http://hdl.handle.net/10948/1194 , Medicinal plants -- South Africa , Materia medica, Vegetable -- South Africa , Diabetes -- Alternative treatment -- South Africa , Plant bioactive compounds , Leonotis leonurus -- Physiological aspects
- Description: Commercial marrubiin, aqueous and organic extracts of Leonotis leonurus were tested in vitro for their anticoagulant and antiplatelet activities. The aqueous extract inhibited platelet aggregation by 69.5 percent (100 μg/mL), while the organic extract (100 μg/mL) and marrubiin (5 μg/mL) showed 92.5 percent and 91.6 percent inhibition, respectively, by inhibiting the binding of fibrinogen to glycoprotein IIb/IIIa receptor in a concentration dependent manner. The extracts significantly prolonged activated partial thromboplastin time compared to untreated plasma controls. Fibrin and D-Dimer formation were drastically decreased. The extracts and marrubiin concentration-dependently inhibited calcium mobilization induced by collagen and thrombin. The formation of thromboxane A2 was also significantly reduced by both the extracts and marrubiin. Protein secretion and platelet adhesion were significantly reduced by both the extracts and marrubiin. The organic extract and marrubiin showed a more pronounced effect than the aqueous extracts in all the in vitro assays. The ex-vivo animal model confirmed the results obtained in vitro. Similar to the in vitro studies, activated partial thromboplastin time clotting time was prolonged by marrubiin and the number of aggregated platelets were significantly reduced relative to aspirin. The findings reflect that marrubiin largely contributes to the organic extract's anticoagulant and antiplatelet effect in vitro. INS-1 cells were cultured under normo- and hyperglycaemic conditions. Marrubiin and the two Leonotis leonurus extracts were screened for anti-diabetic activity in vitro. The stimulatory index of INS-1 cells cultured under hyperglycaemic conditions was significantly increased by 60 percent and 61 percent (p<0.01; n=5) in cells exposed to the organic extract (10 μg/mL) and marrubiin (500 ng/mL), respectively, relative to the normoglycaemic conditions. The gene expression of insulin was significantly increased by 76.5 and 71 percent, and of glucose transporter-2 by 93 and 92.5 percent for marrubiin and the organic extract, respectively, under the same conditions stipulated above (p<0.01; n=4). The extract and marrubiin similarly showed an increase in respiratory rate under hyperglycaemic conditions. Marrubiin increased insulin secretion, HDL-cholesterol, while it decreased total cholesterol, LDL-cholesterol and the atherogenic index in the in vivo rat model.
- Full Text:
- Date Issued: 2010
Production of biologically active recombinant HIV-1 protease and intehrase for the purpose of screening medicianl plant extracts
- Authors: Bosch, Janine
- Date: 2009
- Subjects: Medicinal plants -- South Africa , HIV infections -- Alternative treatment -- South Africa , Materia medica, Vegetable -- South Africa
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:10325 , http://hdl.handle.net/10948/1056 , Medicinal plants -- South Africa , HIV infections -- Alternative treatment -- South Africa , Materia medica, Vegetable -- South Africa
- Description: Human immunodeficiency virus (HIV) and its gradual weakening of the immune system is an ever growing threat. Acquired immune deficiency syndrome (AIDS), the final stage of HIV, renders a person vulnerable to various opportunistic infections, which in the end lead to death. Apart from intensive vaccine studies, treatment research mainly focuses on preventing the individual HIV enzymes (reverse transcriptase, integrase and protease) from performing their functions. Entry inhibitors, however, block viral entry into the cell, while antisense drugs lock onto the viral genome to keep it from functioning. In this study production of active recombinant HIV-1 protease and integrase was attempted for future drug screening programs. HIV-1 protease was cloned into a pET28b(+) vector and expressed in ROSETTA(DE3)pLysS cells. The protein was purified using a nickel-affinity column utilizing the hexa-histidine tag encoded by the vector. Gel filtration chromatography was attempted after refolding of the protease, but protease yield seemed to decrease with the additional purification step. Partially purified protease was characterized with kinetic studies. Kinetic parameters of HIV-1 protease were determined to be Km = 592 μM, Vmax = 0.59 μM/min and kcat = 31 s-1. HIV-1 integrase, which was cloned into a pET15b vector, was expressed in E. coli BL21(DE3) cells. The coding sequence had been mutated to introduce the amino acid substitutions F185K and C280S, increasing solubility of the protein. The first step in purification of this protein was nickel-affinity chromatography, after which cation exchange chromatography was attempted. HIV-1 integrase concentration was low throughout experiments and no clear elution from the cation exchange column could be observed. A non-radioactive enzyme linked HIV-1 integrase assay failed to detect integrase activity. Modifications to future studies of the integrase are suggested in the chapter involved.
- Full Text:
- Date Issued: 2009
- Authors: Bosch, Janine
- Date: 2009
- Subjects: Medicinal plants -- South Africa , HIV infections -- Alternative treatment -- South Africa , Materia medica, Vegetable -- South Africa
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:10325 , http://hdl.handle.net/10948/1056 , Medicinal plants -- South Africa , HIV infections -- Alternative treatment -- South Africa , Materia medica, Vegetable -- South Africa
- Description: Human immunodeficiency virus (HIV) and its gradual weakening of the immune system is an ever growing threat. Acquired immune deficiency syndrome (AIDS), the final stage of HIV, renders a person vulnerable to various opportunistic infections, which in the end lead to death. Apart from intensive vaccine studies, treatment research mainly focuses on preventing the individual HIV enzymes (reverse transcriptase, integrase and protease) from performing their functions. Entry inhibitors, however, block viral entry into the cell, while antisense drugs lock onto the viral genome to keep it from functioning. In this study production of active recombinant HIV-1 protease and integrase was attempted for future drug screening programs. HIV-1 protease was cloned into a pET28b(+) vector and expressed in ROSETTA(DE3)pLysS cells. The protein was purified using a nickel-affinity column utilizing the hexa-histidine tag encoded by the vector. Gel filtration chromatography was attempted after refolding of the protease, but protease yield seemed to decrease with the additional purification step. Partially purified protease was characterized with kinetic studies. Kinetic parameters of HIV-1 protease were determined to be Km = 592 μM, Vmax = 0.59 μM/min and kcat = 31 s-1. HIV-1 integrase, which was cloned into a pET15b vector, was expressed in E. coli BL21(DE3) cells. The coding sequence had been mutated to introduce the amino acid substitutions F185K and C280S, increasing solubility of the protein. The first step in purification of this protein was nickel-affinity chromatography, after which cation exchange chromatography was attempted. HIV-1 integrase concentration was low throughout experiments and no clear elution from the cation exchange column could be observed. A non-radioactive enzyme linked HIV-1 integrase assay failed to detect integrase activity. Modifications to future studies of the integrase are suggested in the chapter involved.
- Full Text:
- Date Issued: 2009
Effect of a South African medicinal plant on antiretroviral drug induced abnormalities in rats
- Authors: Van Gend, Tania Anli
- Date: 2008
- Subjects: Medicinal plants -- South Africa , Antiretroviral agents -- South Africa , Materia medica, Vegetable -- South Africa , HIV infections -- Alternative treatment -- South Africa , Rats as laboratory animals , Rats -- Metabolism
- Language: English
- Type: Thesis , Masters , MTech
- Identifier: vital:10121 , http://hdl.handle.net/10948/1080 , Medicinal plants -- South Africa , Antiretroviral agents -- South Africa , Materia medica, Vegetable -- South Africa , HIV infections -- Alternative treatment -- South Africa , Rats as laboratory animals , Rats -- Metabolism
- Description: The worldwide AIDS epidemic is known to have had a profoundly negative social, economic and personal impact and has taken a heavy toll on existing health care systems, particularly in developing countries. South Africa is experiencing an HIV epidemic with enormous social and economic consequences. Lopinavir/ritonavir antiretroviral treatment has been accredited with having a significantly positive effect and is a key advance in controlling HIV morbidity and mortality. An indigenous South African medicinal plant, Sutherlandia frutescens, known for its anti-diabetic properties and immune-boosting effects, is used for treating HIV positive patients suffering from opportunistic infections. Despite the use of the medicinal plant extract as homeotherapeutic medication, there is little evidence of toxicity testing that identifies its potential for interaction with antiretroviral drugs. However, scientific data relating to the mechanism through which Sutherlandia frutescens acts on the immune system has not been comprehensively documented. The aim of this study was to investigate lopinavir/ritonavir induced metabolic abnormalities in rats and whether the introduction of a plant extract of Sutherlandia frutescens would counteract the side effects of ARV medication. The results indicated that the rodents did not become insulin resistant, however, biochemical analysis indicated that extended ARV drug treatment would have caused insulin resistance. Significant morphological changes were found in the livers, kidneys and pancreases of rats exposed to the lopinavir/ritonavir. Rats exposed to the Sutherlandia frutescens plant extract showed improved histopathology with minimal abnormalities.
- Full Text:
- Date Issued: 2008
- Authors: Van Gend, Tania Anli
- Date: 2008
- Subjects: Medicinal plants -- South Africa , Antiretroviral agents -- South Africa , Materia medica, Vegetable -- South Africa , HIV infections -- Alternative treatment -- South Africa , Rats as laboratory animals , Rats -- Metabolism
- Language: English
- Type: Thesis , Masters , MTech
- Identifier: vital:10121 , http://hdl.handle.net/10948/1080 , Medicinal plants -- South Africa , Antiretroviral agents -- South Africa , Materia medica, Vegetable -- South Africa , HIV infections -- Alternative treatment -- South Africa , Rats as laboratory animals , Rats -- Metabolism
- Description: The worldwide AIDS epidemic is known to have had a profoundly negative social, economic and personal impact and has taken a heavy toll on existing health care systems, particularly in developing countries. South Africa is experiencing an HIV epidemic with enormous social and economic consequences. Lopinavir/ritonavir antiretroviral treatment has been accredited with having a significantly positive effect and is a key advance in controlling HIV morbidity and mortality. An indigenous South African medicinal plant, Sutherlandia frutescens, known for its anti-diabetic properties and immune-boosting effects, is used for treating HIV positive patients suffering from opportunistic infections. Despite the use of the medicinal plant extract as homeotherapeutic medication, there is little evidence of toxicity testing that identifies its potential for interaction with antiretroviral drugs. However, scientific data relating to the mechanism through which Sutherlandia frutescens acts on the immune system has not been comprehensively documented. The aim of this study was to investigate lopinavir/ritonavir induced metabolic abnormalities in rats and whether the introduction of a plant extract of Sutherlandia frutescens would counteract the side effects of ARV medication. The results indicated that the rodents did not become insulin resistant, however, biochemical analysis indicated that extended ARV drug treatment would have caused insulin resistance. Significant morphological changes were found in the livers, kidneys and pancreases of rats exposed to the lopinavir/ritonavir. Rats exposed to the Sutherlandia frutescens plant extract showed improved histopathology with minimal abnormalities.
- Full Text:
- Date Issued: 2008
In vitro testing to investigate the anticoagulant/antithrombotic and antidiabetic biological activity of Leonotis Leonurus
- Authors: Mnonopi, Nandipha Olivia
- Date: 2007
- Subjects: Leonotis leonurus -- Physiological aspects , Medicinal plants -- South Africa , Materia medica, Vegetable -- South Africa , Plant bioactive compounds
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:10331 , http://hdl.handle.net/10948/693 , Leonotis leonurus -- Physiological aspects , Medicinal plants -- South Africa , Materia medica, Vegetable -- South Africa , Plant bioactive compounds
- Description: The rising costs of prescription drugs in the maintenance of personal health and wellbeing have increased the interest in medicinal plants. The World Health Organization estimates that 65 percent-80 percent of the world’s population use traditional medicine as their primary form of health care. In this project the focus has been on the use of Leonotis leonurus extracts as a traditional medicine. The major chemical constituent of this plant is marrubiin, which is a diterpenoid labdane lactone formed from a precursor called premarrubiin. Aqueous and acetone extract (AL and OL extract, respectively) of this plant has been found to have an antithrombotic effect, with IC50 values of 3mg/ml and 6mg/ml, respectively. The extracts also have an effect on fibrinolysis, where the lysis time was decreased by more than 50 percent by the organic extract and standard marrubiin. In whole blood ADP-induced platelet aggregation, the organic extract inhibited aggregation by 68 percent at a final concentration of 138μg/ml (equivalent to 7.2μg/ml marrubiin). Marrubiin has also been screened for antithrombotic/anticoagulant activity; no antithrombotic activity has been observed but it increased the rate of fibrinolysis, by decreasing lysis time by 64 percent and also decreasing fibrin formation. From these findings it can be concluded that marrubiin has a fibrinolytic effect and antiplatelet aggregation effect. In the diabetic studies, in hyperglycemic condition, the OL (10μg/ml) extract and standard marrubiin significantly increased insulin secretion by 200 percent (2-fold) and 400 percent (4-fold), respectively, with respect to the control. The OL extract and standard marrubiin stimulated the release of insulin, the stimulatory index was significantly increased by 450 percent (4.5-fold) and 500 percent (5-fold), respectively, with respect to the control. In the apoptotic studies, in the normoglycemic and hyperglycemic conditions, the OL extract decreased the occurrence of apoptosis, in a dose-dependent manner, with the lower concentrations inducing apoptosis significantly higher than the relevant controls. Standard marrubiin did not have an effect on apoptosis in hyperglycemic condition, but it decreased the occurrence of apoptosis by 200 percent (2-fold) under normoglycemic conditions. The OL extract increased proliferation by 148 percent (1.48- fold) and 155 percent (1.55-fold) in normoglycemic and hyperglycemic conditions, respectively. The same effect was observed for standard marrubiin, where, proliferation was increased by 180 percent (1.8-fold) and 200 percent (2.0-fold) in normoglycemic and hyperglycemic conditions, respectively. RT-PCR displayed that standard marrubiin inhibited the expression of insulin by 50 percent under normoglycemic conditions.
- Full Text:
- Date Issued: 2007
- Authors: Mnonopi, Nandipha Olivia
- Date: 2007
- Subjects: Leonotis leonurus -- Physiological aspects , Medicinal plants -- South Africa , Materia medica, Vegetable -- South Africa , Plant bioactive compounds
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:10331 , http://hdl.handle.net/10948/693 , Leonotis leonurus -- Physiological aspects , Medicinal plants -- South Africa , Materia medica, Vegetable -- South Africa , Plant bioactive compounds
- Description: The rising costs of prescription drugs in the maintenance of personal health and wellbeing have increased the interest in medicinal plants. The World Health Organization estimates that 65 percent-80 percent of the world’s population use traditional medicine as their primary form of health care. In this project the focus has been on the use of Leonotis leonurus extracts as a traditional medicine. The major chemical constituent of this plant is marrubiin, which is a diterpenoid labdane lactone formed from a precursor called premarrubiin. Aqueous and acetone extract (AL and OL extract, respectively) of this plant has been found to have an antithrombotic effect, with IC50 values of 3mg/ml and 6mg/ml, respectively. The extracts also have an effect on fibrinolysis, where the lysis time was decreased by more than 50 percent by the organic extract and standard marrubiin. In whole blood ADP-induced platelet aggregation, the organic extract inhibited aggregation by 68 percent at a final concentration of 138μg/ml (equivalent to 7.2μg/ml marrubiin). Marrubiin has also been screened for antithrombotic/anticoagulant activity; no antithrombotic activity has been observed but it increased the rate of fibrinolysis, by decreasing lysis time by 64 percent and also decreasing fibrin formation. From these findings it can be concluded that marrubiin has a fibrinolytic effect and antiplatelet aggregation effect. In the diabetic studies, in hyperglycemic condition, the OL (10μg/ml) extract and standard marrubiin significantly increased insulin secretion by 200 percent (2-fold) and 400 percent (4-fold), respectively, with respect to the control. The OL extract and standard marrubiin stimulated the release of insulin, the stimulatory index was significantly increased by 450 percent (4.5-fold) and 500 percent (5-fold), respectively, with respect to the control. In the apoptotic studies, in the normoglycemic and hyperglycemic conditions, the OL extract decreased the occurrence of apoptosis, in a dose-dependent manner, with the lower concentrations inducing apoptosis significantly higher than the relevant controls. Standard marrubiin did not have an effect on apoptosis in hyperglycemic condition, but it decreased the occurrence of apoptosis by 200 percent (2-fold) under normoglycemic conditions. The OL extract increased proliferation by 148 percent (1.48- fold) and 155 percent (1.55-fold) in normoglycemic and hyperglycemic conditions, respectively. The same effect was observed for standard marrubiin, where, proliferation was increased by 180 percent (1.8-fold) and 200 percent (2.0-fold) in normoglycemic and hyperglycemic conditions, respectively. RT-PCR displayed that standard marrubiin inhibited the expression of insulin by 50 percent under normoglycemic conditions.
- Full Text:
- Date Issued: 2007
Optimisation of an in vitro model for anti-diabetic screening
- Authors: Wilson, Gayle Pamela
- Date: 2006
- Subjects: Hypoglycemic agents , Diabetes -- Treatment -- South Africa , Materia medica, Vegetable -- South Africa
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:10308 , http://hdl.handle.net/10948/428 , Hypoglycemic agents , Diabetes -- Treatment -- South Africa , Materia medica, Vegetable -- South Africa
- Description: The need for alternative strategies for the prevention and treatment of diabetes is growing rapidly as type II diabetes is reaching epidemic status in our society. This need was the basis for the creation of this study, as it was necessary to start looking towards medicinal plants as potential antidiabetic treatment and no comprehensive in vitro model existed. In creating a model for determining the effects of alternative traditional medicines as antidiabetic potentiates, it was necessary that two metabolic pathways, namely glucose uptake and insulin secretion, which play a significant role in glucose homeostasis, be at the centre of our investigations. The objective of this project was to optimize the methodology required to screen and ultimately determine the effectiveness of the plant extracts Kankerbos and MRC2003, as antidiabetic potentiates, through observing their effects on glucose utilisation and insulin secretion. If these medicinal plants are going to make a positive contribution to the health of type II diabetic South Africans, then the determination of their efficacy is essential. The cell lines used in this study included 3T3-L1 preadipocytes, Chang liver, C2C12 muscle and INS-1 rat pancreatic cells. Each cell line represents a different in vivo organ that is known to have an influence on glucose homeostasis in our bodies, each with its own unique metabolic pathways and mechanisms of activity, thereby making each one a vital component in the study. The positive controls for the two models were insulin and metformin (glucose utilisation) and glibenclamide (insulin secretion). Insulin was shown to provide a significant increase in the amount of glucose taken up in C2C12 muscle and Chang liver cells for acute conditions. Chronic treatments with metformin provided a significant increase in glucose utilised by Chang liver cells. Glibenclamide was an effective positive control for stimulating insulin secretion by INS-1 cells under acute conditions as there was a significant increase in the amount of insulin secreted. MRC2003 did not show any significant antidiabetic activity. Sutherlandia frutescens (Kankerbos) showed biological activities comparable to some of the more recognized antidiabetic compounds throughout the study. With regards to the glucose utilisation model, Kankerbos was seen to have both acute and chronic effects in different cell lines. In the C2C12 muscle cell line, Kankerbos significantly increased glucose uptake when they were exposed to acute conditions. Kankerbos also had a significant effect on the Chang liver cells as it was observed that under both acute and chronic conditions, this plant extract induced the uptake of glucose into these cells. With respect to the insulin secretion model involving INS-1 cells, no significant effect was seen during acute exposure with Kankerbos treatment. However during chronic exposure, an increase in insulin secretion was initiated by this plant extract. Overall, the results of this study suggest that Kankerbos has a twofold mechanism of action for its glucose-lowering effects. Given that Kankerbos is widely available in South Africa, this study was valuable as it provided an indication that Kankerbos has antidiabetic activities and could possibly be used as an alternative antidiabetic medication.
- Full Text:
- Date Issued: 2006
- Authors: Wilson, Gayle Pamela
- Date: 2006
- Subjects: Hypoglycemic agents , Diabetes -- Treatment -- South Africa , Materia medica, Vegetable -- South Africa
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:10308 , http://hdl.handle.net/10948/428 , Hypoglycemic agents , Diabetes -- Treatment -- South Africa , Materia medica, Vegetable -- South Africa
- Description: The need for alternative strategies for the prevention and treatment of diabetes is growing rapidly as type II diabetes is reaching epidemic status in our society. This need was the basis for the creation of this study, as it was necessary to start looking towards medicinal plants as potential antidiabetic treatment and no comprehensive in vitro model existed. In creating a model for determining the effects of alternative traditional medicines as antidiabetic potentiates, it was necessary that two metabolic pathways, namely glucose uptake and insulin secretion, which play a significant role in glucose homeostasis, be at the centre of our investigations. The objective of this project was to optimize the methodology required to screen and ultimately determine the effectiveness of the plant extracts Kankerbos and MRC2003, as antidiabetic potentiates, through observing their effects on glucose utilisation and insulin secretion. If these medicinal plants are going to make a positive contribution to the health of type II diabetic South Africans, then the determination of their efficacy is essential. The cell lines used in this study included 3T3-L1 preadipocytes, Chang liver, C2C12 muscle and INS-1 rat pancreatic cells. Each cell line represents a different in vivo organ that is known to have an influence on glucose homeostasis in our bodies, each with its own unique metabolic pathways and mechanisms of activity, thereby making each one a vital component in the study. The positive controls for the two models were insulin and metformin (glucose utilisation) and glibenclamide (insulin secretion). Insulin was shown to provide a significant increase in the amount of glucose taken up in C2C12 muscle and Chang liver cells for acute conditions. Chronic treatments with metformin provided a significant increase in glucose utilised by Chang liver cells. Glibenclamide was an effective positive control for stimulating insulin secretion by INS-1 cells under acute conditions as there was a significant increase in the amount of insulin secreted. MRC2003 did not show any significant antidiabetic activity. Sutherlandia frutescens (Kankerbos) showed biological activities comparable to some of the more recognized antidiabetic compounds throughout the study. With regards to the glucose utilisation model, Kankerbos was seen to have both acute and chronic effects in different cell lines. In the C2C12 muscle cell line, Kankerbos significantly increased glucose uptake when they were exposed to acute conditions. Kankerbos also had a significant effect on the Chang liver cells as it was observed that under both acute and chronic conditions, this plant extract induced the uptake of glucose into these cells. With respect to the insulin secretion model involving INS-1 cells, no significant effect was seen during acute exposure with Kankerbos treatment. However during chronic exposure, an increase in insulin secretion was initiated by this plant extract. Overall, the results of this study suggest that Kankerbos has a twofold mechanism of action for its glucose-lowering effects. Given that Kankerbos is widely available in South Africa, this study was valuable as it provided an indication that Kankerbos has antidiabetic activities and could possibly be used as an alternative antidiabetic medication.
- Full Text:
- Date Issued: 2006
In vitro anti-HIV activities of Sutherlandia frutescens and Lobostemon trigonum extracts
- Authors: Harnett, Siobhán Margaret
- Date: 2004
- Subjects: Medicinal plants -- South Africa , Materia medica, Vegetable -- South Africa , HIV infections -- Alternative treatment -- South Africa
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:11072 , http://hdl.handle.net/10948/347 , Medicinal plants -- South Africa , Materia medica, Vegetable -- South Africa , HIV infections -- Alternative treatment -- South Africa
- Description: Currently, the approved anti-HIV drugs on the market only target the three HIV enzymes: reverse transcriptase, protease and more recently, integrase. Due to the limited nature of the current therapy, it is possible that a multi-drug resistant virus can emerge. The main concerns in developing countries however, are the expense and availability of the drugs and because of this, it is essential to investigate all alternatives. Traditional medicine offers many advantages as compared to allopathic treatment in so far as being relatively cheaper, accessible and it is broadly accepted in the population groups of the developing countries. Little is known though, of the exact efficacy and toxicity of these remedies so it is vital that these possible leads be investigated thoroughly. For the purpose of this study, two plants, Sutherlandia frutescens and Lobostemon trigonum were studied to ascertain their potential anti-HIV activity. Sutherlandia has received international attention as a possible cheap herbal remedy to improve the health of AIDS sufferers. Anecdotal evidence from health workers claim that HIV- infected patients on Sutherlandia treatment have shown improved CD4 counts, decreased viral loads and a general improvement in well-being. Extracts were prepared from dried leaves and flowers in methanol, ethanol, acetone, methylene dichloride or distilled water. Sulphated polysaccharides have been described extensively in literature with regards to their anti-HIV activity, so as a form of dereplication; an ethanol precipitation was performed on the aqueous extracts to remove sulphated polysaccharides. A toxicity study was performed on all crude extracts using uninfected peripheral mononuclear blood cells (PBMCs) isolated from whole blood. To measure anti-HIV activity, HIV-infected PBMCs were cultured with each of the crude extracts and cell viability measured using the tetrazolium salt, XTT. HIV-infected CEM-NKR-CCR5 cells were also used and supernatant from the viral studies was tested for the HIV antigen p24. xii Results varied greatly between assays but with the inclusion of a point-scale system to evaluate the extracts it was clear that overall the organic extracts of the Sutherlandia flowers, especially the acetone extract (SFA), showed great anti-HIV potential. SFA in every case decreased p24 levels and in the toxicity study did not decrease cell proliferation. With the HIV-infected PBMCs SFA actually helped improve cell proliferation despite the infection. To determine the specific anti- HIV activity, all crude extracts were tested for inhibition of HIV-I reverse transcriptase, the glycohydrolase enzymes: a-glucosidase, ß-glucosidase, ßglucuronidase, HIV-I integrase and HIV-II protease. No significant inhibition was seen with these experiments except for the HIV-I RT assay. The aqueous extract of the Lobostemon leaves produced an inhibitor of HIV-RT with a very low IC50 value of 0.049mg/ml. Some inhibitory effect was lost with the removal of the sulphated polysaccharides and the addition of BSA to the assay, but still 64% inhibition of the HIVRT remained, which confirmed that the inhibitor could be something novel, and not of the polysaccharide or tannin compounds.
- Full Text:
- Date Issued: 2004
- Authors: Harnett, Siobhán Margaret
- Date: 2004
- Subjects: Medicinal plants -- South Africa , Materia medica, Vegetable -- South Africa , HIV infections -- Alternative treatment -- South Africa
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:11072 , http://hdl.handle.net/10948/347 , Medicinal plants -- South Africa , Materia medica, Vegetable -- South Africa , HIV infections -- Alternative treatment -- South Africa
- Description: Currently, the approved anti-HIV drugs on the market only target the three HIV enzymes: reverse transcriptase, protease and more recently, integrase. Due to the limited nature of the current therapy, it is possible that a multi-drug resistant virus can emerge. The main concerns in developing countries however, are the expense and availability of the drugs and because of this, it is essential to investigate all alternatives. Traditional medicine offers many advantages as compared to allopathic treatment in so far as being relatively cheaper, accessible and it is broadly accepted in the population groups of the developing countries. Little is known though, of the exact efficacy and toxicity of these remedies so it is vital that these possible leads be investigated thoroughly. For the purpose of this study, two plants, Sutherlandia frutescens and Lobostemon trigonum were studied to ascertain their potential anti-HIV activity. Sutherlandia has received international attention as a possible cheap herbal remedy to improve the health of AIDS sufferers. Anecdotal evidence from health workers claim that HIV- infected patients on Sutherlandia treatment have shown improved CD4 counts, decreased viral loads and a general improvement in well-being. Extracts were prepared from dried leaves and flowers in methanol, ethanol, acetone, methylene dichloride or distilled water. Sulphated polysaccharides have been described extensively in literature with regards to their anti-HIV activity, so as a form of dereplication; an ethanol precipitation was performed on the aqueous extracts to remove sulphated polysaccharides. A toxicity study was performed on all crude extracts using uninfected peripheral mononuclear blood cells (PBMCs) isolated from whole blood. To measure anti-HIV activity, HIV-infected PBMCs were cultured with each of the crude extracts and cell viability measured using the tetrazolium salt, XTT. HIV-infected CEM-NKR-CCR5 cells were also used and supernatant from the viral studies was tested for the HIV antigen p24. xii Results varied greatly between assays but with the inclusion of a point-scale system to evaluate the extracts it was clear that overall the organic extracts of the Sutherlandia flowers, especially the acetone extract (SFA), showed great anti-HIV potential. SFA in every case decreased p24 levels and in the toxicity study did not decrease cell proliferation. With the HIV-infected PBMCs SFA actually helped improve cell proliferation despite the infection. To determine the specific anti- HIV activity, all crude extracts were tested for inhibition of HIV-I reverse transcriptase, the glycohydrolase enzymes: a-glucosidase, ß-glucosidase, ßglucuronidase, HIV-I integrase and HIV-II protease. No significant inhibition was seen with these experiments except for the HIV-I RT assay. The aqueous extract of the Lobostemon leaves produced an inhibitor of HIV-RT with a very low IC50 value of 0.049mg/ml. Some inhibitory effect was lost with the removal of the sulphated polysaccharides and the addition of BSA to the assay, but still 64% inhibition of the HIVRT remained, which confirmed that the inhibitor could be something novel, and not of the polysaccharide or tannin compounds.
- Full Text:
- Date Issued: 2004
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