Effect of Artesunate on Leishmania Amazonesis Induced Neuroinflammation and Nociceptive Behavior in Male Balb/C Mice

SIMPLE SUMMARY: Leishmaniasis is a multisystemic zoonotic disease with several symptoms, and treating this disease is a great challenge for veterinary medicine. Artemisinin derivatives are currently the most widely used drugs for the treatment of malaria, especially for their excellent safety profile and low cost. Artesunate is a more stable derivative of its precursor, artemisin, and has been shown to be a pluripotent agent with different pharmacological actions. In this study, we evaluated the role of neuroinflammation in leishmaniasis and its correlation with pain and sickness behavior, and the anti-inflammatory and neuroprotective effects of artesunate in a murine model of Leishmania amazonensis infection in BALB/c mice. The results from this study indicate that artesunate is a good candidate for treatment and/or as an adjuvant in anti- leishmaniasis therapy, and for preventing and alleviating leishmaniasis-induced pain and neuroinflammation. ABSTRACT: Background: Leishmaniasis is a multisystemic zoonotic disease with several symptoms, including neurological disorders. Leishmaniasis is accompanied by an increase in nociceptive behaviors, linked to the presence of a chronic inflammatory state, in both peripheral tissue and the central nervous system. Artesunate is a more stable derivative of its precursor artemisin and has been shown to be a pluripotent agent with different pharmacological actions. Methods: In this study, we investigated the effects of artesunate in Leishmania amazonensi- infected BALB/c mice, evaluating its effectiveness in reducing inflammation, neuroinflammation, and nociceptive and sickness behaviors. Results: Our results demonstrate a significant increase in pain sensitivity and sickness behaviors after L. amazonensis infection. Moreover, the infection induced a significant increase in inflammatory response at both the paw and spinal cord level. Treatment with artesunate was able to induce a significant decrease in tissue inflammation and neuroinflammation and thus induce a significant decrease in pain sensitivity and sickness behaviors. Conclusions: The results from this study indicate that artesunate is a good candidate for treatment and/or as an adjuvant in leishmanicidal therapy, and to prevent and alleviate leishmaniasis-induced pain and neuroinflammation and thereby improve the quality of life of leishmaniasis patients.