1. Repurposing antimalarial artesunate for the prophylactic treatment of depression: Evidence from preclinical research.
- Author
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Huang S, Galaj E, Wang J, Guo Y, Wang S, Shi M, Yin X, Liu K, Luo Y, Meng L, and Shi H
- Subjects
- Mice, Animals, Artesunate pharmacology, Artesunate therapeutic use, Antioxidants pharmacology, Lipopolysaccharides pharmacology, Inflammation drug therapy, Disease Models, Animal, Behavior, Animal, Depression etiology, Antimalarials pharmacology, Antimalarials therapeutic use
- Abstract
Introduction: Several studies have linked inflammation and oxidative stress with the pathogenesis of depression. Artesunate is a commonly used medication to treat malaria and has been shown to produce antioxidant, anti-inflammatory, and immunomodulatory effects. However, its prophylactic effects on depression and depression-related brain pathology are unknown., Methods: In Experiment 1, using a PC12 cell line, we investigated whether artesunate can prevent hydrogen peroxide (H
2 O2 )-induced oxidative injury that mimics oxidative stress commonly observed in the depressed brain. Next, using lipopolysaccharide (LPS)-induced mouse model of depression, we investigated whether artesunate can prevent behavioral deficits observed in the open field test, novelty-suppressed feeding test, sucrose preference test, forced swimming test, and tail suspension procedure., Results: We found that artesunate significantly prevented a H2 O2 -induced reduction in PC12 cell activity, suggesting its antioxidant potential. We also found that mice pretreated with artesunate (5, 15 mg/kg) intraperitoneally (i.p.) prior to the LPS (.8 mg/kg, i.p.) treatment showed fewer and less severe depression- and anxiety-like behaviors than the LPS-treated control mice., Conclusion: Our findings indicate that artesunate produces antioxidant effect, as well as antidepressant and anxiolytic effects. Importantly, our findings first demonstrate that artesunate can prevent LPS-induced depression- and anxiety-like symptoms, strongly suggesting its prophylactic potential in the treatment of depression and, perhaps, other psychiatric disorders associated with inflammation and oxidative stress., (© 2022 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)- Published
- 2023
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