Scholarlink

<p>In this article, we explored the mechanism of curcumin (CUR) in mitigating airway inflammation in a mouse model of chronic obstructive pulmonary disease (COPD) based on the peroxisome proliferator-activated receptor γ (PPARγ)/adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin complex 1 (mTORC1) pathway. A COPD mouse model was established <i>via</i> smoke exposure &amp; intratracheal instillation of lipopolysaccharide. Mice were administered the CUR, the PPARγ knockdown adeno-associated virus, or the PPARγ inhibitor GW9662. Bronchoalveolar lavage fluid (BALF) was collected, and the lung wet-to-dry (W/D) weight ratio was measured. Inflammatory cell counts and inflammatory factors in BALF were assessed by a hemocytometer and ELISA. The binding pattern between CUR and PPARγ was analyzed by molecular docking and further verified by drug affinity responsive target stability assay, and pulmonary PPARγ, p-AMPK/AMPK, and p-mTOR/mTOR levels were detected by western blot assay. COPD mice showed elevated lung tissue W/D ratio, BALF interleukin-8, tumor necrosis factor α levels, and white blood cell, lymphocyte, and neutrophil counts, with prominent inflammatory cell infiltration, thickened alveolar wall, and noticeable pulmonary interstitial edema and congestion. Importantly, CUR treatment significantly ameliorated these changes. CUR upregulated PPARγ by directly binding to PPARγ with strong binding affinity, enhanced AMPK phosphorylation, and suppressed mTOR activity. In contrast, PPARγ knockdown or inhibition reduced p-AMPK, increased p-mTOR, aggravated inflammation and lung damage, and partially reversed the beneficial effects of CUR. CUR directly binds to PPARγ to activate AMPK to inhibit mTORC1 activity, thereby ameliorating airway inflammation in COPD mice.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

The inhibitory effect of curcumin on airway inflammation in mice with chronic obstructive pulmonary disease and its mechanism: a study based on the PPARγ/AMPK/mTORC1 pathway

  • 期刊论文

  • 发表日期：

    2026年6月26日

查看全文
  • Mengjuan Wang,
  • Kaifeng Zhang,
  • Yujia Zhang,
  • Yue Gu,
  • Chaoying Liu

摘要

In this article, we explored the mechanism of curcumin (CUR) in mitigating airway inflammation in a mouse model of chronic obstructive pulmonary disease (COPD) based on the peroxisome proliferator-activated receptor γ (PPARγ)/adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin complex 1 (mTORC1) pathway. A COPD mouse model was established via smoke exposure & intratracheal instillation of lipopolysaccharide. Mice were administered the CUR, the PPARγ knockdown adeno-associated virus, or the PPARγ inhibitor GW9662. Bronchoalveolar lavage fluid (BALF) was collected, and the lung wet-to-dry (W/D) weight ratio was measured. Inflammatory cell counts and inflammatory factors in BALF were assessed by a hemocytometer and ELISA. The binding pattern between CUR and PPARγ was analyzed by molecular docking and further verified by drug affinity responsive target stability assay, and pulmonary PPARγ, p-AMPK/AMPK, and p-mTOR/mTOR levels were detected by western blot assay. COPD mice showed elevated lung tissue W/D ratio, BALF interleukin-8, tumor necrosis factor α levels, and white blood cell, lymphocyte, and neutrophil counts, with prominent inflammatory cell infiltration, thickened alveolar wall, and noticeable pulmonary interstitial edema and congestion. Importantly, CUR treatment significantly ameliorated these changes. CUR upregulated PPARγ by directly binding to PPARγ with strong binding affinity, enhanced AMPK phosphorylation, and suppressed mTOR activity. In contrast, PPARγ knockdown or inhibition reduced p-AMPK, increased p-mTOR, aggravated inflammation and lung damage, and partially reversed the beneficial effects of CUR. CUR directly binds to PPARγ to activate AMPK to inhibit mTORC1 activity, thereby ameliorating airway inflammation in COPD mice.