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This study evaluated the efficacy of 50\u2009mg\/kg purified anacardic acids (AAs), isolated from cashew nut shell liquid, on multiple steps of oxidative stress and inflammation induced by rotenone in the <jats:italic>substantia nigra<\/jats:italic> (SN) and striatum. Adult mice were divided into four groups: Control, rotenone, AAs\u2009+\u2009rotenone, and AAs alone. Lipoperoxidation, nitric oxide (NO) levels, and reduced glutathione (GSH)\/oxidized gluthatione (GSSG) ratio were evaluated. NF\u2010kB\u2010p65, pro\u2010IL\u20101\u03b2, cleaved IL\u20101\u03b2, metalloproteinase\u20109, Tissue Inhibitory Factor\u20101 (TIMP\u20101), tyrosine hydroxylase (TH), and glial fibrillary acidic protein (GFAP) levels were assessed by Western blot. In silico studies were also made using the SwissADME web tool. Rotenone increased lipoperoxidation and NO production and reduced TH levels and GSH\/GSSG ratio in both SN and striatum. It also enhanced NF\u2010kB\u2010p65, pro, and cleaved IL\u20101\u03b2, MMP\u20109, GFAP levels compared to control and AAs groups. The AAs alone reduced pro\u2010IL\u20101\u03b2 in the striatum while they augmented TIMP1 and reduced MMP\u20109 amounts in both regions. AAs reversed rotenone\u2010induced effects on lipoperoxidation, NO production, and GSH\/GSSG ratio, as well as increased TH and attenuated pro\u2010IL\u20101\u03b2 and MMP\u20109 levels in both regions, NF\u2010kB\u2010p65 in the SN and GFAP in the striatum. Altogether, the in vivo and in silico analysis reinforced multiple and defined molecular targets of AAs, identifying that they are promising neuroprotective drug candidates for PD, acting against oxidative and inflammatory conditions induced by rotenone.<\/jats:p>","DOI":"10.1002\/iub.2304","type":"journal-article","created":{"date-parts":[[2020,5,25]],"date-time":"2020-05-25T06:41:37Z","timestamp":1590388897000},"page":"1765-1779","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Purified anacardic acids exert multiple neuroprotective effects in pesticide model of Parkinson's disease: in vivo and in silico analysis"],"prefix":"10.1002","volume":"72","author":[{"given":"Ricielle L.","family":"Augusto","sequence":"first","affiliation":[{"name":"Departamento de Fisiologia e Farmacologia Universidade Federal de Pernambuco, UFPE  Recife Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid P.","family":"Mendon\u00e7a","sequence":"additional","affiliation":[{"name":"Departamento de Fisiologia e Farmacologia Universidade Federal de Pernambuco, UFPE  Recife Brazil"},{"name":"Departamento de Entomologia, Laborat\u00f3rio de Ultraestrutura Instituto Aggeu Magalh\u00e3es\u2010FIOCRUZ  Recife Brazil"},{"name":"Instituto Nacional de Ci\u00eancia e Tecnologia de Neuroimunomodula\u00e7\u00e3o (NIM)  Rio de Janeiro Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel N.","family":"de Albuquerque Rego","sequence":"additional","affiliation":[{"name":"Departamento de Fisiologia e Farmacologia Universidade Federal de Pernambuco, UFPE  Recife Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle D.","family":"Pereira","sequence":"additional","affiliation":[{"name":"Departamento de Fisiologia e Farmacologia Universidade Federal de Pernambuco, UFPE  Recife Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00edlian V.","family":"da Penha Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Departamento de Fisiologia e Farmacologia Universidade Federal de Pernambuco, UFPE  Recife Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria L.","family":"dos Santos","sequence":"additional","affiliation":[{"name":"Instituto de Qu\u00edmica, Divis\u00e3o de Qu\u00edmica org\u00e2nica, Universidade de Bras\u00edlia, UnB  Brasilia Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raphael F.","family":"de Souza","sequence":"additional","affiliation":[{"name":"Departamento de Fisiologia e Farmacologia Universidade Federal de Pernambuco, UFPE  Recife Brazil"},{"name":"Departamento de Educa\u00e7\u00e3o F\u00edsica Universidade Federal de Sergipe, UFS  S\u00e3o Crist\u00f3vam Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giselle M. 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