Journal
PHYTOTHERAPY RESEARCH
Volume 32, Issue 9, Pages 1795-1802Publisher
WILEY
DOI: 10.1002/ptr.6113
Keywords
apigenin; cytotoxicity; metabolic pathways; Plasmodium berghei
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Funding
- Zanjan University of Medical Sciences [A-12-153-11]
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Due to the challenges in the control, prevention, and eradication of parasitic diseases like malaria, there is an urgent need to discover new therapeutic agents. Plant-derived medicines may open new ways in the field of antiplasmodial therapy. This study is aimed to investigate the toxicity and in vivo antiplasmodial activity of apigenin, a dietary flavonoid. Apigenin cytotoxicity was investigated on Huh7 cell line, brine shrimp (Artemia salina) larva, and human red blood cells. In vivo toxicity of apigenin was assessed by metabolomics approaches. Apigenin exhibited significant suppression of parasitemia in a dose-dependent manner; it suppressed Plasmodium berghei growth by 69.74%, 50.3%, and 49.23% at concentrations of 70, 35, and 15mg/kg/day, respectively. The IC50 value for apigenin after 24hr exposure to Huh7 cells was 225g/ml. Apigenin did not show noticeable toxicity on A.salina and also on the membrane integrity of red blood cells. After 24hr exposure of mice to apigenin, alterations were seen in the metabolism of glucocorticoids and mineralocorticoids, bile acid metabolism (alternative pathway), sulfur metabolism, bile acid metabolism, metabolism of estrogens and androgens, cholesterol catabolism, and biosynthesis of cholesterol. These findings indicate that apigenin has potential in vivo antiplasmodial activity against P.berghei infected mice with high selectivity against malaria, but it can disrupt some metabolic pathways in mice.
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