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

Inflammation. 2021 Dec;44(6):2217-2231. doi: 10.1007/s10753-021-01494-z. Epub 2021 Jun 18.

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.

Keywords: NLRP3 inflammasome; Schizandrin B; airway inflammation; airway remodeling; asthma; macrophage; miR-135a-5p; pyroptosis.

MeSH terms

  • Airway Remodeling / drug effects*
  • Animals
  • Anti-Asthmatic Agents / pharmacology*
  • Anti-Inflammatory Agents / pharmacology*
  • Asthma / drug therapy*
  • Asthma / metabolism
  • Asthma / pathology
  • Asthma / physiopathology
  • Cells, Cultured
  • Cyclooctanes / pharmacology
  • Disease Models, Animal
  • Female
  • Inflammasomes / antagonists & inhibitors*
  • Inflammasomes / metabolism
  • Lignans / pharmacology*
  • Lung / drug effects*
  • Lung / metabolism
  • Lung / pathology
  • Lung / physiopathology
  • Macrophages, Alveolar / drug effects
  • Macrophages, Alveolar / metabolism
  • Macrophages, Alveolar / pathology
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • NF-kappa B / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein / antagonists & inhibitors*
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • Pneumonia / metabolism
  • Pneumonia / pathology
  • Pneumonia / physiopathology
  • Pneumonia / prevention & control*
  • Polycyclic Compounds / pharmacology*
  • Pyroptosis / drug effects*
  • Rats
  • Rats, Sprague-Dawley
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction
  • TRPC Cation Channels / metabolism

Substances

  • Anti-Asthmatic Agents
  • Anti-Inflammatory Agents
  • Cyclooctanes
  • Inflammasomes
  • Lignans
  • MIRN135 microRNA, rat
  • MicroRNAs
  • NF-kappa B
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, mouse
  • Polycyclic Compounds
  • STAT3 Transcription Factor
  • Stat3 protein, rat
  • TRPC Cation Channels
  • schizandrin B