Artesunate and Tetramethylpyrazine Exert Effects on Experimental Cerebral Malaria in a Mechanism of Protein S‑Nitrosylation
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 eff...
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| Veröffentlicht in: | ACS infectious diseases 2021-10, Vol.7 (10), p.2836-2849 |
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| creator | Zheng, Zhongyuan Liu, Hui Wang, Xi Zhang, Yu Qu, Shuiqing Yang, Yuanmin Deng, Shuoqiu Chen, Lina Zhu, Xiaoxin Li, Yujie |
| description | 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. |
| doi_str_mv | 10.1021/acsinfecdis.1c00085 |
| format | Article |
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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.</description><identifier>ISSN: 2373-8227</identifier><identifier>EISSN: 2373-8227</identifier><identifier>DOI: 10.1021/acsinfecdis.1c00085</identifier><identifier>PMID: 34254783</identifier><language>eng</language><publisher>WASHINGTON: American Chemical Society</publisher><subject>Artesunate ; Chemistry, Medicinal ; Humans ; Infectious Diseases ; Life Sciences & Biomedicine ; Malaria, Cerebral - drug therapy ; Nitric Oxide ; Pharmacology & Pharmacy ; Protein S ; Pyrazines ; Science & Technology</subject><ispartof>ACS infectious diseases, 2021-10, Vol.7 (10), p.2836-2849</ispartof><rights>2021 American Chemical Society</rights><woscitedreferencessubscribed>true</woscitedreferencessubscribed><woscitedreferencescount>2</woscitedreferencescount><woscitedreferencesoriginalsourcerecordid>wos000707979000008</woscitedreferencesoriginalsourcerecordid><citedby>FETCH-LOGICAL-a345t-746a38a091a7bfca7709d310ca9b0c88ff1afdb57f8a41c3db1b7ba13fe01ee13</citedby><cites>FETCH-LOGICAL-a345t-746a38a091a7bfca7709d310ca9b0c88ff1afdb57f8a41c3db1b7ba13fe01ee13</cites><orcidid>0000-0002-6806-4110</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/acsinfecdis.1c00085$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/acsinfecdis.1c00085$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>315,781,785,2766,27080,27928,27929,56742,56792</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34254783$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zheng, Zhongyuan</creatorcontrib><creatorcontrib>Liu, Hui</creatorcontrib><creatorcontrib>Wang, Xi</creatorcontrib><creatorcontrib>Zhang, Yu</creatorcontrib><creatorcontrib>Qu, Shuiqing</creatorcontrib><creatorcontrib>Yang, Yuanmin</creatorcontrib><creatorcontrib>Deng, Shuoqiu</creatorcontrib><creatorcontrib>Chen, Lina</creatorcontrib><creatorcontrib>Zhu, Xiaoxin</creatorcontrib><creatorcontrib>Li, Yujie</creatorcontrib><title>Artesunate and Tetramethylpyrazine Exert Effects on Experimental Cerebral Malaria in a Mechanism of Protein S‑Nitrosylation</title><title>ACS infectious diseases</title><addtitle>ACS INFECT DIS</addtitle><addtitle>ACS Infect. Dis</addtitle><description>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.</description><subject>Artesunate</subject><subject>Chemistry, Medicinal</subject><subject>Humans</subject><subject>Infectious Diseases</subject><subject>Life Sciences & Biomedicine</subject><subject>Malaria, Cerebral - drug therapy</subject><subject>Nitric Oxide</subject><subject>Pharmacology & Pharmacy</subject><subject>Protein S</subject><subject>Pyrazines</subject><subject>Science & Technology</subject><issn>2373-8227</issn><issn>2373-8227</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>HGBXW</sourceid><sourceid>EIF</sourceid><recordid>eNqNkNFKHTEQhkNpqWJ9goLkUihHk81uk72U5dQW1BZqr5dJdoKR3eSYZGlPQegr-Io-SaPnVLyS5ibD8P0z__yEvOfsiLOKH4NJzls0g0tH3DDGVPOK7FZCioWqKvn6Wb1D9lO6LggXqqnr5i3ZEXXV1FKJXXJ7EjOm2UNGCn6gl5gjTJiv1uNqHeG380iXvzBmurRlXU40-NJYYXQT-gwj7TCijqU4hxGiA-o8BXqO5gq8SxMNln6LIWNpf7__c3fhcgxpPUJ2wb8jbyyMCfe3_x758Wl52X1enH09_dKdnC1A1E1eyPojCAWs5SC1NSAlawfBmYFWM6OUtRzsoBtpFdTciEFzLTVwYZFxRC72yOFm7iqGmxlT7ieXDI4jeAxz6qum4RVTlWIFFRvUFJspou1X5VSI656z_iH6_ln0_Tb6ojrYLpj1hMOT5l_QBVAb4CfqYJNx6A0-YWWIZLKVLXt4qnP5MZ4uzD4X6Yf_lxb6eEMXm_11mKMvwb7o_S-re7cR</recordid><startdate>20211008</startdate><enddate>20211008</enddate><creator>Zheng, Zhongyuan</creator><creator>Liu, Hui</creator><creator>Wang, Xi</creator><creator>Zhang, Yu</creator><creator>Qu, Shuiqing</creator><creator>Yang, Yuanmin</creator><creator>Deng, Shuoqiu</creator><creator>Chen, Lina</creator><creator>Zhu, Xiaoxin</creator><creator>Li, Yujie</creator><general>American Chemical Society</general><general>Amer Chemical Soc</general><scope>BLEPL</scope><scope>DTL</scope><scope>HGBXW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-6806-4110</orcidid></search><sort><creationdate>20211008</creationdate><title>Artesunate and Tetramethylpyrazine Exert Effects on Experimental Cerebral Malaria in a Mechanism of Protein S‑Nitrosylation</title><author>Zheng, Zhongyuan ; Liu, Hui ; Wang, Xi ; Zhang, Yu ; Qu, Shuiqing ; Yang, Yuanmin ; Deng, Shuoqiu ; Chen, Lina ; Zhu, Xiaoxin ; Li, Yujie</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a345t-746a38a091a7bfca7709d310ca9b0c88ff1afdb57f8a41c3db1b7ba13fe01ee13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Artesunate</topic><topic>Chemistry, Medicinal</topic><topic>Humans</topic><topic>Infectious Diseases</topic><topic>Life Sciences & Biomedicine</topic><topic>Malaria, Cerebral - drug therapy</topic><topic>Nitric Oxide</topic><topic>Pharmacology & Pharmacy</topic><topic>Protein S</topic><topic>Pyrazines</topic><topic>Science & Technology</topic><toplevel>online_resources</toplevel><creatorcontrib>Zheng, Zhongyuan</creatorcontrib><creatorcontrib>Liu, Hui</creatorcontrib><creatorcontrib>Wang, Xi</creatorcontrib><creatorcontrib>Zhang, Yu</creatorcontrib><creatorcontrib>Qu, Shuiqing</creatorcontrib><creatorcontrib>Yang, Yuanmin</creatorcontrib><creatorcontrib>Deng, Shuoqiu</creatorcontrib><creatorcontrib>Chen, Lina</creatorcontrib><creatorcontrib>Zhu, Xiaoxin</creatorcontrib><creatorcontrib>Li, Yujie</creatorcontrib><collection>Web of Science Core Collection</collection><collection>Science Citation Index Expanded</collection><collection>Web of Science - Science Citation Index Expanded - 2021</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>ACS infectious diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zheng, Zhongyuan</au><au>Liu, Hui</au><au>Wang, Xi</au><au>Zhang, Yu</au><au>Qu, Shuiqing</au><au>Yang, Yuanmin</au><au>Deng, Shuoqiu</au><au>Chen, Lina</au><au>Zhu, Xiaoxin</au><au>Li, Yujie</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Artesunate and Tetramethylpyrazine Exert Effects on Experimental Cerebral Malaria in a Mechanism of Protein S‑Nitrosylation</atitle><jtitle>ACS infectious diseases</jtitle><stitle>ACS INFECT DIS</stitle><addtitle>ACS Infect. 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| subjects | Artesunate Chemistry, Medicinal Humans Infectious Diseases Life Sciences & Biomedicine Malaria, Cerebral - drug therapy Nitric Oxide Pharmacology & Pharmacy Protein S Pyrazines Science & Technology |
| title | Artesunate and Tetramethylpyrazine Exert Effects on Experimental Cerebral Malaria in a Mechanism of Protein S‑Nitrosylation |
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