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Title:	In vitro and in vivo studies on the anti-malarial activity of aqueous extract of momordica charantia and elucidation of its mechanism of action via cytokine modulation involving host GSK3B inhibition
Authors:	Ali Mayada Hussain (P84096)
Supervisor:	Izyanti Ibrahim, Dr.
Keywords:	Antimalarials Malaria Universiti Kebangsaan Malaysia -- Dissertations Dissertations, Academic -- Malaysia
Issue Date:	4-Apr-2022
Description:	Malaria is a life-threatening endemic disease in many parts of the world. The infection which is caused by Plasmodium sp. and a cause of global morbidity and mortality is associated with dysregulation of inflammatory cytokines production. Momordica charantia is a medicinal plant traditionally used in South-East Asia and Africa to treat many conditions. Extracts of the plant have been shown to exhibit anti-inflammatory, anti-cancer and anti-hyperglycemic effects. Some active compounds identified in M. charantia display glycogen synthase kinase-3 (GSK3)-inhibitory activities based on in silico docking and binding studies. GSK3 is a serine / threonine kinase which plays an important role in regulating the inflammatory process. The aim of this study is to evaluate M. charantia fruit aqueous extract for in vitro anti-plasmodial activity using cultures of Plasmodium falciparum 3D7 and in vivo anti-malarial effects in a murine model of malaria (Plasmodium berghei NK65) infection. Whether the mechanism of action of M. charantia involves inhibition of host GSK3β was also investigated. Additionally, the anti-malarial activity of M. charantia extract in combination with the standard anti-malarial drug chloroquine (CQ) was also investigated in vivo. Quercetin as an active compound was separated and quantitated from an aqueous extract of M. charantia via HPLC. The M. charantia extract suppressed growth of P. falciparum cultures with a selectivity index value exceeding 10. Intra-peritoneal administration of the extract at different doses (50, 75 and 100 mg/kg bw) into P. berghei- infected mice for four consecutive days resulted in doses-dependent manner (57.90�2.90, 60.90�2.71 and 70.20�2.13) and improved median survival time (18, 21 and 22) respectively. M. charantia extract administration into infected mice resulted in significantly increased level of phosphorylated GSK3β (Ser9) in liver of infected mice. Phosphorylated Akt (Ser473) was increased, whereas phosphorylated NF-κB (Ser536) was decreased in liver of infected mice treated with M. charantia extract compared with control. In addition, M. charantia extract decreased levels of pro- inflammatory cytokines IFN-γ, TNF-α and IL-18 in serum. In contrast, levels of anti-inflammatory cytokines IL-10 and IL-4 were increased. Furthermore, M. charantia treatment improved infection-induced histopathological changes of the liver in experimental animals. Chloroquine-M. charantia combination treatment in malaria-infected mice also showed anti-malarial effect. Findings from the present study indicate that the anti-malarial mechanism of M. charantia involved inhibition of host GSK3β mediated by Akt. This reiterates the importance of GSK3 as a plausible therapeutic target to address inflammation-related conditions. Moreover, the combination treatment with chloroquine enhanced the anti-malarial activity of M. charantia as a medicinal plant suggesting the potential use of M. charantia in adjunctive treatment for malaria.,Ph.D
Pages:	190
Call Number:	QR201.M3A435 2022 tesis
Publisher:	UKM, Bangi
Appears in Collections:	Faculty of Science and Technology / Fakulti Sains dan Teknologi

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