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Schisandrin B Attenuates Airway Inflammation and Airway Remodeling in Asthma by Inhibiting NLRP3 Inflammasome Activation and Reducing Pyroptosis

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Abstract

Asthma is a chronic inflammatory disorder of the airways. Schisandrin B (SB) is the main effective component. This study investigated the effects of SB on airway inflammation and airway remodeling in asthma. The rat model of asthma was established. The rats were treated with SB to evaluate the effects of SB on airway inflammation, airway remodeling, NLRP3 inflammasome activation, and pyroptosis. Alveolar macrophages of rats were isolated, and the macrophage inflammatory model was established by lipopolysaccharide (LPS) induction. The LPS-induced macrophages were treated with SB. The binding relationship between miR-135a-5p and TPRC1 was analyzed. LPS + SB-treated macrophages were transfected with miR-135a-5p inhibitor. The expressions of key factors of the STAT3/NF-κB pathway were detected. SB reduced airway inflammation and airway remodeling in asthmatic rats. SB inhibited NLRP3 inflammasome activation and reduced pyroptosis in asthmatic rats and LPS-induced macrophages. SB reversely regulated the miR-135a-5p/TRPC1 axis. Downregulation of miR-135a-5p attenuated the inhibitory effect of SB on NLRP3 inflammasome activation. SB inhibited the STAT3/NF-κB pathway via the miR-135a-5p/TRPC1 axis. In conclusion, SB inhibited NLRP3 inflammasome activation and reduced pyroptosis via the miR-135a-5p/TRPC1/STAT3/NF-κB axis, thus alleviating airway inflammation and airway remodeling in asthma. This study may confer novel insights for the management of asthma.

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Data Availability

The datasets and materials used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This work was supported by the National Natural Science Foundation of China [grant number 81804144], the Shanghai Municipal Key Clinical Specialty [grant number shslczdzk04102], the Young Talents Clinical Ability Improvement Project of Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine [grant number RC-2020-01-01], and the National TCM Clinical Research Base of Longhua Hospital affiliated to Shanghai University of Traditional Chinese Medicine [grant number LYTD-90].

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Authors and Affiliations

  1. Department of Pediatrics, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, No.725 Wanping South Road, Xuhui District, Shanghai, 200032, China

    Xiufeng Chen, Zhen Xiao, Zhiyan Jiang, Yonghong Jiang, Wen Li & Mingjing Wang

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  1. Xiufeng Chen
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  2. Zhen Xiao
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  3. Zhiyan Jiang
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Contributions

Xiufeng Chen: Conceptualization, Methodology. Zhen Xiao: Data curation, Writing- Original draft preparation. Zhiyan Jiang: Investigation. Yonghong Jiang: Supervision. Wen Li: Software. Mingjing Wang: Writing- Reviewing and Editing.

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Correspondence to Zhen Xiao or Zhiyan Jiang.

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This study got the permission of the Ethical Committee of Longhua Hospital. All the animal experiments were implemented on the guide for the care and use of laboratory animals and on minimized animal number and the least pains.

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Not applicable.

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The authors declare no competing interests.

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Chen, X., Xiao, Z., Jiang, Z. et al. Schisandrin B Attenuates Airway Inflammation and Airway Remodeling in Asthma by Inhibiting NLRP3 Inflammasome Activation and Reducing Pyroptosis. Inflammation 44, 2217–2231 (2021). https://doi.org/10.1007/s10753-021-01494-z

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  • DOI: https://doi.org/10.1007/s10753-021-01494-z

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