Repurposing antimalarial artesunate for the prophylactic treatment of depression: Evidence from preclinical research

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 (H2O2)-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 H2O2-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.