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Dihydrotanshinone Attenuates LPS-Induced Acute Lung Injury in Mice by Upregulating LXRα

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Abstract—

Dihydrotanshinone (DIH) is an extract of Salvia miltiorrhiza Bunge. It has been reported that DIH could regulate NF-κB signaling pathway. The aim of this study was to investigate whether DIH could protect mice from lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. In this study, sixty mice were randomly divided into five groups, one group as blank control group, the second group as LPS control group, and the last three groups were pre-injected with different doses of DIH and then inhaled LPS for experimental comparison. After 12 h of LPS treatment, the wet-dry ratio, histopathlogical changes, and myeloperoxidase (MPO) activity of lungs were measured. In addition, ELISA kits were used to measure the levels of TNF-α and IL-1β inflammatory cytokines in bronchoalveolar lavage fluids (BALF), and western blot analysis was used to measure the activity of NF-κB signaling pathway. The results demonstrated that DIH could effectively reduce pulmonary edema, MPO activity, and improve the lung histopathlogical changes. Furthermore, DIH suppressed the levels of inflammatory cytokines in BALF, such as TNF-α and IL-1β. In addition, DIH could also downregulate the activity of NF-κB signaling pathway. We also found that DIH dose-dependently increased the expression of LXRα. In addition, DIH could inhibit LPS-induced IL-8 production and NF-κB activation in A549 cells. And the inhibitory effects were reversed by LXRα inhibitor geranylgeranyl pyrophosphate (GGPP). Therefore, we speculate that DIH regulates LPS-induced ALI in mice by increasing LXRα expression, which subsequently inhibiting NF-κB signaling pathway.

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The data used to support the findings of this study are available from the corresponding author upon request.

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Authors and Affiliations

  1. Department of Anesthesiology, The Second Affiliated Hospital of Jilin University, Changchun, China

    Jing Yue

  2. Department of Head and Neck Surgery, The Second Affiliated Hospital of Jilin University, Changchun, China

    Kai Su, Chengbi Xu & Xueshibojie Liu

  3. Department of Thoracic Surgery, The Second Affiliated Hospital of Jilin University, Changchun, China

    Guangxin Zhang

  4. Department of Hepatobiliary Pancreatic Surgery, China-Japan Friendship Hospital of Jilin University, Changchun, China

    Jinghui Yang

  5. Department of Head and Neck Surgery, The Second Affiliated Hospital of Jilin University, Changchun, China

    Xueshibojie Liu

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  1. Jing Yue
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  2. Kai Su
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  3. Guangxin Zhang
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  4. Jinghui Yang
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  5. Chengbi Xu
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  6. Xueshibojie Liu
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Contributions

Xueshibojie Liu designed the experiment; Xueshibojie Liu, Jinghui Yang, Jing Yue, Guangxin Zhang, and Kai Su did the experiment; Chengbi Xu analyzed the data; Xueshibojie Liu wrote the paper; Jing Yue, Kai Su, and Guangxin Zhang revised the paper.

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Correspondence to Xueshibojie Liu.

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All the experimental protocols in this study were approved by the Institutional Animal Care and Use Committee of Jilin University. All authors consent to participate this research.

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Yue, J., Su, K., Zhang, G. et al. Dihydrotanshinone Attenuates LPS-Induced Acute Lung Injury in Mice by Upregulating LXRα. Inflammation 45, 212–221 (2022). https://doi.org/10.1007/s10753-021-01539-3

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