4.7 Article

Abscisic acid suppresses the activation of NLRP3 inflammasome and oxidative stress in murine allergic airway inflammation

Journal

PHYTOTHERAPY RESEARCH
Volume 35, Issue 6, Pages 3298-3309

Publisher

WILEY
DOI: 10.1002/ptr.7051

Keywords

abscisic acid; allergic airway inflammation; mitochondrial fusion; fission; NLRP3 inflammasome; oxidative stress; PPAR‐ γ

Funding

  1. National Natural Science Foundation of China [81770032, 81870036]
  2. Key Lab of Geriatric Molecular Medicine of Anhui Province
  3. Program for the Youth Distinguished Talents of Anhui Medical University
  4. Foundation for Distinguished Young Scholars of the First Affiliated Hospital of Anhui Medical University

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ABA shows efficacy against allergic airway inflammation by inhibiting NLRP3 inflammasome and oxidative stress in a PPAR-gamma dependent manner. This suggests the potential of ABA or ABA-rich food in protecting against asthma.
Abscisic acid (ABA), a well-known natural phytohormone reportedly exerts anti-inflammatory and anti-oxidative properties in diabetes and colitis. However, the efficacy of ABA against allergic airway inflammation and the underlying mechanism remain unknown. Herein, an OVA-induced murine allergic airway inflammation model was established and treated with ABA in the presence or absence of PPAR-gamma antagonist GW9662. The results showed that ABA effectively stunted the development of airway inflammation, and concordantly downregulated OVA-induced activation of NLRP3 inflammasome, suppressed oxidative stress and decreased the expression of mitochondrial fusion/fission markers including Optic Atrophy 1 (OPA1), Mitofusion 2 (Mfn2), dynamin-related protein 1 (DRP1) and Fission 1 (Fis1). Moreover, ABA treatment further increased OVA-induced expression of PPAR-gamma, while GW9662 abrogated the inhibitory effect of ABA on allergic airway inflammation as well as on the activation of NLRP3 inflammasome and oxidative stress. Consistently, ABA inhibited the activation of NLRP3 inflammasome, suppressed oxidative stress and mitochondrial fusion/fission in LPS-stimulated Raw264.7 cells via PPAR-gamma. Collectively, ABA ameliorates OVA-induced allergic airway inflammation in a PPAR-gamma dependent manner, and such effect of ABA may be associated with its inhibitory effect on NLRP3 inflammasome and oxidative stress. Our results suggest the potential of ABA or ABA-rich food in protecting against asthma.

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