Investigating the anti-inflammatory effects of plant derived compounds in tuberculosis using the THP-1 macrophage model

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dc.contributor.advisorNdlovu, Hlumani
dc.contributor.authorRajh, Caryn
dc.date.accessioned2024-06-03T07:42:45Z
dc.date.available2024-06-03T07:42:45Z
dc.date.issued2023
dc.date.updated2024-06-03T07:31:43Z
dc.description.abstractBackground Tuberculosis (TB) is a highly communicable disease that is caused by the bacillus, Mycobacterium tuberculosis. TB is responsible for devastating morbidity and mortality worldwide, especially in the developing world. TB can be effectively treated with the currently available drugs; however, poor adherence to therapy and the emergence of drug resistant bacteria has significantly impaired efforts to eradicate TB. Therefore, new therapies and therapeutic strategies are required to combat TB. One of the proposed new strategies is to develop host-directed therapies (HDTs) that are aimed at boosting the host's innate ability to fight the infection and ameliorate the deleterious tissue pathology associated with advanced TB. Repurposed drugs and plant-derived compounds with antiinflammatory effects have been explored for potential use as HDT's. Objectives To evaluate the anti-inflammatory effects of plant-derived compounds in macrophages infected with live Mtb strain H37Rv. Results We found that Ruscogenin failed to modulate cytokine secretion in macrophages that were either infected with live Mtb strain H37Rv or macrophages that were pre-treated with the compound prior to infection with Mtb, except for lowering IL-6 secretion. Leonurine significantly lowered the levels of IL-1β, TNF and IL-6 in macrophages that were pre-treated with the compound for 24 hours prior to infection with live Mtb. We also showed that Withaferin A decreased IL-1β and IL-6 secretion in macrophages infected with Mtb prior to treatment with the compound. Finally, pre-treating macrophages with Withaferin A prior to infection with Mtb decreased the secretion of TNF and IL-6 compared to the untreated and infected macrophages. Conclusion Leonurine and Withaferin A appear to possess anti-inflammatory effects in macrophages infected with live Mtb. Their potential use as HDTs needs to be explored further in animal models.
dc.identifier.apacitationRajh, C. (2023). <i>Investigating the anti-inflammatory effects of plant derived compounds in tuberculosis using the THP-1 macrophage model</i>. (). ,Faculty of Health Sciences ,Department of Clinical Laboratory Sciences. Retrieved from http://hdl.handle.net/11427/39826en_ZA
dc.identifier.chicagocitationRajh, Caryn. <i>"Investigating the anti-inflammatory effects of plant derived compounds in tuberculosis using the THP-1 macrophage model."</i> ., ,Faculty of Health Sciences ,Department of Clinical Laboratory Sciences, 2023. http://hdl.handle.net/11427/39826en_ZA
dc.identifier.citationRajh, C. 2023. Investigating the anti-inflammatory effects of plant derived compounds in tuberculosis using the THP-1 macrophage model. . ,Faculty of Health Sciences ,Department of Clinical Laboratory Sciences. http://hdl.handle.net/11427/39826en_ZA
dc.identifier.ris TY - Thesis / Dissertation AU - Rajh, Caryn AB - Background Tuberculosis (TB) is a highly communicable disease that is caused by the bacillus, Mycobacterium tuberculosis. TB is responsible for devastating morbidity and mortality worldwide, especially in the developing world. TB can be effectively treated with the currently available drugs; however, poor adherence to therapy and the emergence of drug resistant bacteria has significantly impaired efforts to eradicate TB. Therefore, new therapies and therapeutic strategies are required to combat TB. One of the proposed new strategies is to develop host-directed therapies (HDTs) that are aimed at boosting the host's innate ability to fight the infection and ameliorate the deleterious tissue pathology associated with advanced TB. Repurposed drugs and plant-derived compounds with antiinflammatory effects have been explored for potential use as HDT's. Objectives To evaluate the anti-inflammatory effects of plant-derived compounds in macrophages infected with live Mtb strain H37Rv. Results We found that Ruscogenin failed to modulate cytokine secretion in macrophages that were either infected with live Mtb strain H37Rv or macrophages that were pre-treated with the compound prior to infection with Mtb, except for lowering IL-6 secretion. Leonurine significantly lowered the levels of IL-1β, TNF and IL-6 in macrophages that were pre-treated with the compound for 24 hours prior to infection with live Mtb. We also showed that Withaferin A decreased IL-1β and IL-6 secretion in macrophages infected with Mtb prior to treatment with the compound. Finally, pre-treating macrophages with Withaferin A prior to infection with Mtb decreased the secretion of TNF and IL-6 compared to the untreated and infected macrophages. Conclusion Leonurine and Withaferin A appear to possess anti-inflammatory effects in macrophages infected with live Mtb. Their potential use as HDTs needs to be explored further in animal models. DA - 2023 DB - OpenUCT DP - University of Cape Town KW - Medicine LK - https://open.uct.ac.za PY - 2023 T1 - Investigating the anti-inflammatory effects of plant derived compounds in tuberculosis using the THP-1 macrophage model TI - Investigating the anti-inflammatory effects of plant derived compounds in tuberculosis using the THP-1 macrophage model UR - http://hdl.handle.net/11427/39826 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/39826
dc.identifier.vancouvercitationRajh C. Investigating the anti-inflammatory effects of plant derived compounds in tuberculosis using the THP-1 macrophage model. []. ,Faculty of Health Sciences ,Department of Clinical Laboratory Sciences, 2023 [cited yyyy month dd]. Available from: http://hdl.handle.net/11427/39826en_ZA
dc.language.rfc3066eng
dc.publisher.departmentDepartment of Clinical Laboratory Sciences
dc.publisher.facultyFaculty of Health Sciences
dc.subjectMedicine
dc.titleInvestigating the anti-inflammatory effects of plant derived compounds in tuberculosis using the THP-1 macrophage model
dc.typeThesis / Dissertation
dc.type.qualificationlevelMasters
dc.type.qualificationlevelMSc
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