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The aim of present investigation was to evaluate the potential and possible mechanism of action of pinitol against lipopolysaccharide (LPS)\u2010induced pneumonia in the experimental animal model. Pneumonia was induced in Sprague\u2010Dawley rats by intratracheal administration of LPS (2\u2009mg\/kg). Animals were treated with either vehicle or dexamethasone or pinitol (5 or 10 or 20\u2009mg\/kg). Potential of pinitol against LPS\u2010induced pulmonary insult was assessed based on behavioral, biochemical, molecular, and ultrastructural studies. Intratracheal instillation of LPS induced significant (<jats:italic>P<\/jats:italic>\u2009&lt;\u2009.05) inflammatory infiltration in\u00a0bronchoalveolar lavage fluid (BALF) and lung tissue reflected by elevated pleural effusion volume, lung edema, BALF polymorphonuclear leukocytes count and lung myeloperoxidase levels, which was attenuated by pinitol (10 and 20\u2009mg\/kg) administration. Pinitol also markedly (<jats:italic>P<\/jats:italic>\u2009&lt;\u2009.05) inhibited LPS\u2010induced alterations in electrocardiographic, hemodynamic changes, right ventricular, and lung function tests. The LPS\u2010induced downregulated nuclear factor erythroid 2\u2013related factor 2 (Nrf\u20102) and heme oxygenase\u20101 (HO\u20101), whereas upregulated transforming growth factor\u2010\u03b2 (TGF\u2010\u03b2), tumor necrosis factor\u2010\u03b1 (TNF\u2010\u03b1), interleukin\u20101\u03b2 (IL\u20101\u03b2), IL\u20106, NOD\u2010, LRR\u2010, and pyrin domain\u2010containing protein 3 (NLRP3), and inducible nitric oxide synthase (iNOs) lung messenger RNA expressions were significantly (<jats:italic>P<\/jats:italic>\u2009&lt;\u2009.05) inhibited by pinitol. Western blot analysis suggested pinitol markedly (<jats:italic>P<\/jats:italic>\u2009&lt;\u2009.05) decreased nuclear factor\u2010\u03baB (NF\u2010\u03baB), inhibitor of nuclear factor \u03baB (IkB\u03b1), toll\u2010like receptor 4 (TLR\u20104), and cyclooxygenase\u2010II (COX\u2010II) protein expressions in the lung. These findings were further supported by histological and ultrastructural analyses of lung tissue that show\u00a0pinitol significantly (<jats:italic>P<\/jats:italic>\u2009&lt;\u2009.05) ameliorates LPS\u2010induced aberrations in lung tissue. In conclusion, pinitol attenuated LPS\u2010induced pneumonia via inhibition of TLR\u20104 to downregulate the NF\u2010\u03baB\/I\u03baB\u03b1 signaling cascade and thus ameliorated the production of proinflammatory cytokines (TNF\u2010\u03b1, ILs, NLRP3, and TGF\u2010\u03b2), inflammatory mediators (COX\u2010II and iNOs) and elevated oxidative stress (Nrf\u20102 and HO\u20101).<\/jats:p>","DOI":"10.1002\/jbt.22622","type":"journal-article","created":{"date-parts":[[2020,9,25]],"date-time":"2020-09-25T15:34:37Z","timestamp":1601048077000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Pinitol attenuates LPS\u2010induced pneumonia in experimental animals: Possible role via inhibition of the TLR\u20104 and NF\u2010\u03baB\/I\u03baB\u03b1 signaling cascade pathway"],"prefix":"10.1002","volume":"35","author":[{"given":"Yingying","family":"Fan","sequence":"first","affiliation":[{"name":"The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Center for Mitochondrial Biology and Medicine, School of Life Science and Technology Xi'an Jiaotong University  Xi'an Shaanxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2014Head and Neck Surgery, Xijing Hospital Air Force Medical University  Xi'an Shaanxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhihui","family":"Feng","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Center for Mitochondrial Biology and Medicine, School of Life Science and Technology Xi'an Jiaotong University  Xi'an Shaanxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ke","family":"Cao","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Center for Mitochondrial Biology and Medicine, School of Life Science and Technology Xi'an Jiaotong University  Xi'an Shaanxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6913-1154","authenticated-orcid":false,"given":"Hao","family":"Xu","sequence":"additional","affiliation":[{"name":"Basic of Medical Science Xi'an Medical University  Xi'an Shaanxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiankang","family":"Liu","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Center for Mitochondrial Biology and Medicine, School of Life Science and Technology Xi'an Jiaotong University  Xi'an Shaanxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,9,14]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)60222-6"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.3904\/kjim.2015.30.6.829"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofy010"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.4161\/cib.29053"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/1465-9921-14-92"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2016.1230584"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.2174\/1874467212666190102105052"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcrc.2009.12.007"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10753-014-9930-1"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.04.00139803"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12640-020-00187-z"},{"key":"e_1_2_9_13_1","first-page":"138","volume":"518","author":"Shah U. 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