Oxidative stress and genes regulation of cerebral malaria upon Zizyphus spina-christi treatment in a murine model.
The development and spread of multidrug-resistant strains of malarial parasites have led to an overwhelming increase in the resistance to current antimalarial drugs. The urgent need for alternative antimalarial drugs has directed some of the current studies toward folkloric medicine approaches. Interestingly, the Zizyphus spina Cristi leaf extract (ZLE) has been found to exhibit antiplasmodial activity. This study evaluated the protective effect of ZLE against Plasmodium berghei-induced cerebral tissue injuries in mice. Male C57Bl/6 mice received an injection of P. berghei-infected red blood cells. Mice were divided into three groups (control, infected, and ZLE-treated), and were subjected to histological, biochemical, and molecular analyses. Murine malaria infections induced significant weight loss; however, upon ZLE treatment, the weight of mice was markedly restored. Additionally, infected mice showed brain histopathological changes and induction of oxidative damage. Significantly, ZLE treatment restored the levels of oxidative markers and antioxidant enzyme to the normal ranges. The mRNA expression of several genes in the brain of mice including Cacnb4, Adam23, Glrb, Vdac3, and Cabp1 was significantly upregulated during P. berghei infection. In contrast, ZLE markedly reduced the mRNA expression of these genes. To conclude, the results indicate that ZLE could play an important role in reducing the destructive effect of P. berghei-induced cerebral malaria owing to its antiplasmodial and antioxidant activities.
Clinical Laboratory Sciences Department, College of Applied Medical Sciences, King Saud University, Saudi Arabia. Electronic address: mmubaraki@ksu.edu.sa.
Murad A
MA
Mubaraki
Clinical Laboratory Sciences Department, College of Applied Medical Sciences, King Saud University, Saudi Arabia.
Taghreed A
TA
Hafiz
Department of Zoology, College of Science, King Saud University, Saudi Arabia.
Saleh
S
Al-Quraishy
Department of Zoology, College of Science, King Saud University, Saudi Arabia; Department of Zoology and Entomology, Faculty of Science, Helwan University, Egypt.
Mohamed A
MA
Dkhil
D051722:ADAM Proteins / Q000235:genetics; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D000975:Antioxidants; D001921:Brain / Q000473:pathology / Q000503:physiopathology; D015220:Calcium Channels / Q000235:genetics; D002135:Calcium-Binding Proteins / Q000235:genetics; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects*; D008288:Malaria / Q000188:drug therapy / Q000469:parasitology; D016779:Malaria, Cerebral / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D033681:Mitochondrial Membrane Transport Proteins / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D018384:Oxidative Stress / Q000187:drug effects*; D010936:Plant Extracts / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry; D010962:Plasmodium berghei / Q000187:drug effects / Q000472:pathogenicity; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics; D018009:Receptors, Glycine / Q000235:genetics; D015854:Up-Regulation; D050994:Voltage-Dependent Anion Channels / Q000235:genetics; D031957:Ziziphus / Q000737:chemistry*
D000962:Antimalarials; D000975:Antioxidants; C491530:Cacnb4 protein, mouse; D015220:Calcium Channels; D002135:Calcium-Binding Proteins; C491949:Glrb protein, mouse; D033681:Mitochondrial Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D010936:Plant Extracts; D012333:RNA, Messenger; D018009:Receptors, Glycine; C480078:Vdac3 protein, mouse; D050994:Voltage-Dependent Anion Channels; D051722:ADAM Proteins; C121259:Adam23 protein, mouse; C085577:Ca2+-binding protein-1
Apoptosis; Cerebral malaria; Mice; Oxidative stress; Plasmodium berghei; Zizyphus spina-christi