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
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
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
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
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
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