Pneumonia is a chronic disorder of the respiratory system associated with worsening quality of life and a significant economic burden. Pinitol, a plant cyclic polyol, has been documented for immune‐inflammatory potential. The aim of present investigation was to evaluate the potential and possible mechanism of action of pinitol against lipopolysaccharide (LPS)‐induced pneumonia in the experimental animal model. Pneumonia was induced in Sprague‐Dawley rats by intratracheal administration of LPS (2 mg/kg). Animals were treated with either vehicle or dexamethasone or pinitol (5 or 10 or 20 mg/kg). Potential of pinitol against LPS‐induced pulmonary insult was assessed based on behavioral, biochemical, molecular, and ultrastructural studies. Intratracheal instillation of LPS induced significant (P < .05) inflammatory infiltration in bronchoalveolar 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 mg/kg) administration. Pinitol also markedly (P < .05) inhibited LPS‐induced alterations in electrocardiographic, hemodynamic changes, right ventricular, and lung function tests. The LPS‐induced downregulated nuclear factor erythroid 2–related factor 2 (Nrf‐2) and heme oxygenase‐1 (HO‐1), whereas upregulated transforming growth factor‐β (TGF‐β), tumor necrosis factor‐α (TNF‐α), interleukin‐1β (IL‐1β), IL‐6, NOD‐, LRR‐, and pyrin domain‐containing protein 3 (NLRP3), and inducible nitric oxide synthase (iNOs) lung messenger RNA expressions were significantly (P < .05) inhibited by pinitol. Western blot analysis suggested pinitol markedly (P < .05) decreased nuclear factor‐κB (NF‐κB), inhibitor of nuclear factor κB (IkBα), toll‐like receptor 4 (TLR‐4), and cyclooxygenase‐II (COX‐II) protein expressions in the lung. These findings were further supported by histological and ultrastructural analyses of lung tissue that show pinitol significantly (P < .05) ameliorates LPS‐induced aberrations in lung tissue. In conclusion, pinitol attenuated LPS‐induced pneumonia via inhibition of TLR‐4 to downregulate the NF‐κB/IκBα signaling cascade and thus ameliorated the production of proinflammatory cytokines (TNF‐α, ILs, NLRP3, and TGF‐β), inflammatory mediators (COX‐II and iNOs) and elevated oxidative stress (Nrf‐2 and HO‐1).

中文翻译：

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松醇可减轻LPS诱导的实验动物的肺炎：可能通过抑制TLR-4和NF-κB/IκBα信号级联途径发挥作用。

肺炎是呼吸系统的慢性疾病，与生活质量下降和重大的经济负担有关。Pinitol是一种植物环状多元醇，已被证明具有免疫发炎的潜力。本研究的目的是评估在实验动物模型中松醇对脂多糖（LPS）诱导的肺炎的作用的潜在机制。通过气管内施用LPS（2 mg / kg）在Sprague-Dawley大鼠中诱发肺炎。用赋形剂或地塞米松或松醇（5或10或20mg / kg）治疗动物。根据行为，生化，分子和超微结构研究，评估了松醇对LPS诱发的肺部损伤的潜力。气管内注射LPS诱导显着（P <.05）胸膜积液量增加，肺水肿，BALF多形核白细胞计数和肺髓过氧化物酶水平升高反映了支气管肺泡灌洗液（BALF）和肺组织中的炎性浸润，而松果糖醇（10和20 mg / kg）给药减弱了炎症浸润。松醇也显着（P <.05）抑制LPS引起的心电图改变，血流动力学改变，右心室和肺功能测试。LPS诱导的核因子红系2相关因子2（Nrf-2）和血红素加氧酶-1（HO-1）的下调，而转化生长因子β（TGF-β），肿瘤坏死因子α（TNF- α），白介素-1β（IL-1β），IL-6，NOD-，LRR-和含吡啶结构域蛋白3（NLRP3）以及诱导型一氧化氮合酶（iNOs）肺信使RNA的表达均显着（P  < .05）被松糖醇抑制。蛋白质印迹分析表明松醇明显（P <.05）降低了肺中核因子κB（NF-κB），核因子κB抑制剂（IkBα），toll​​样受体4（TLR-4）和环氧合酶II（COX-II）蛋白的表达。这些发现得到了肺组织的组织学和超微结构分析的进一步支持，这些分析表明松醇可以显着（P  <.05）改善LPS引起的肺组织畸变。总之，松果醇通过抑制TLR-4来下调NF-κB/IκBα信号级联，从而减轻LPS诱导的肺炎，从而改善促炎细胞因子（TNF-α，IL，NLRP3和TGF-β），炎性介质的产生。 （COX-II和iNOs）和升高的氧化应激（Nrf-2和HO-1）。