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However, the mechanistic pathways underlying boldenone\u2010induced behavioral deviations and neuronal toxicity have not yet been elucidated. On the other hand, the natural polyphenol curcumin is appreciated for its relative safety, potent antioxidant activity, and anti\u2010inflammatory properties. Therefore, the present study was initiated to explore the signaling pathways underlying boldenone\u2010induced anxiety and aggression in rats, and the protective effects of curcumin. To achieve this aim, male Wistar albino rats were randomly distributed into control, curcumin (100\u2009mg\/kg in sesame oil, p.o., once daily), boldenone (5\u2009mg\/kg, intramuscular, once weekly), and combination groups. Rats were challenged across the open field, irritability, defensive aggression, and resident\u2010intruder tests. The prefrontal cortex was used to assess serotonin level, oxidative stress markers, and mRNA expression of myeloid differentiation primary response gene (MyD88), TNFR\u2010associated factor 6 (TRAF\u20106), tumor necrosis factor \u03b1 (TNF\u2010\u03b1), interleukin\u20101\u03b2 (IL\u20101\u03b2), protein expression of toll\u2010like receptor 4 (TLR4), and phosphorylated nuclear factor\u2010\u03baB transcription factor (NF\u2010\u03baB p65). Unprecedented, the current results showed that boldenone elicited aggression in rats accompanied by depleted serotonin, enhanced oxidative stress, and exaggerated inflammatory response via upregulation of TLR4\/MyD88\/TRAF\u20106\/NF\u2010\u03baB pathway. Interestingly, curcumin mitigated boldenone\u2010induced neurobehavioral disturbances in rats, normalized the oxidant\/antioxidant balance, and suppressed TLR4\/MyD88\/TRAF\u20106\/NF\u2010\u03baB pathway and its downstream proinflammatory signaling molecules TNF\u2010\u03b1 and IL\u20101\u03b2.<\/jats:p>","DOI":"10.1002\/jbt.22936","type":"journal-article","created":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T06:51:19Z","timestamp":1635749479000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Inhibition of boldenone\u2010induced aggression in rats by curcumin: Targeting TLR4\/MyD88\/TRAF\u20106\/NF\u2010\u03baB pathway"],"prefix":"10.1002","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9752-6556","authenticated-orcid":false,"given":"Marwa E.","family":"El\u2010Shamarka","sequence":"first","affiliation":[{"name":"Department of Narcotics, Ergogenic Aids and Poisons National Research Center  Dokki Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hesham A.","family":"Eliwa","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences and Drug Manufacturing Misr University for Science and Technology (MUST)  Giza Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4359-2080","authenticated-orcid":false,"given":"Maha A. 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