['To evaluate the effects of artesunate on organ injury and dysfunction associated with hemorrhagic shock (HS) in the rat.', 'HS is still a common cause of death in severely injured patients and is characterized by impairment of organ perfusion, systemic inflammatory response, and multiple organ failure. There is no specific therapy that reduces organ injury/dysfunction. Artesunate exhibits pharmacological actions beyond its antimalarial activity, such as anticancer, antiviral, and anti-inflammatory effects.', 'Rats were submitted to HS. Mean arterial pressure was reduced to 30\u200amm Hg for 90\u200aminutes, followed by resuscitation. Rats were randomly treated with artesunate (2.4 or 4.8\u200amg/kg i.v.) or vehicle upon resuscitation. Four hours later, parameters of organ injury and dysfunction were assessed.', 'Artesunate attenuated the multiple organ injury and dysfunction caused by HS. Pathway analysis of RNA sequencing provided good evidence to support an effect of artesunate on the Akt-survival pathway, leading to downregulation of interleukin-1 receptor-associated kinase 1. Using Western blot analysis, we confirmed that treatment of HS rats with artesunate enhanced the phosphorylation (activation) of Protein kinase B (Akt) and endothelial nitric oxide synthase and the phosphorylation (inhibition) of glycogen synthase kinase-3β (GSK-3β). Moreover, artesunate attenuated the HS-induced activation of nuclear factor kappa B and reduced the expression of proinflammatory proteins (inducible nitric oxide synthase, tumor necrosis factor-α, and interleukin 6).'] Does artesunate protect Against the Organ Injury and Dysfunction Induced by Severe Hemorrhage and Resuscitation?