4.5 Article

Artesunate and Tetramethylpyrazine Exert Effects on Experimental Cerebral Malaria in a Mechanism of Protein S-Nitrosylation

Journal

ACS INFECTIOUS DISEASES
Volume 7, Issue 10, Pages 2836-2849

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/acsinfecdis.1c00085

Keywords

experimental cerebral malaria; artesunate; tetramethylpyrazine; nitric oxide; S-nitrosothiols

Funding

  1. National Natural Science Foundation of China [81841001,81803814]
  2. Major National Science and Technology Program of China for Innovative Drug [2017ZX09101002-001-001-3]

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This study confirmed the effects of AS+TMP on cerebral blood flow and NO-related indicators, and explored the mechanism of NO through the S-nitrosoproteome. The results demonstrated that AS+TMP could improve ECM symptoms.
Cerebral malaria (CM) is caused by Plasmodium falciparum, resulting in severe sequelae; one of its pathogenic factors is the low bioavailability of nitric oxide (NO). Our previous study suggested that the combination of artesunate (AS) and tetramethylpyrazine (TMP) exerts an adjuvant therapeutic effect on the symptoms of experimental CM (ECM) and that NO regulation plays an important role. In the present study, we further verified the effects of AS+TMP on cerebral blood flow (CBF) and detected NO-related indicators. We focused on the role of NO through S-nitrosoproteome based on previous proteomics data and explored the mechanism of AS+TMP for improving pathological ECM symptoms. We observed that AS+TMP reduces adhesion, increases CBF, and regulates NO synthase (NOS) activity, thereby regulating the level of S-nitrosothiols, such as metabolism-related or neuro-associated receptors, for improving ECM symptoms. These results demonstrated that AS+TMP could be an effective strategy in adjuvant therapy of CM.

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