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

Abstract

Abscisic acid (ABA), a well-known natural phytohormone reportedly exerts antiinflammatory 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-γ antagonist GW9662. The results showed that ABA effectively stunted the development of airway inflammation, and concordantly downregulated OVAinduced 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-γ, 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-γ. Collectively, ABA ameliorates OVA-induced allergic airway inflammation in a PPAR-γ 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.

Modulatory Properties of Food and Nutraceutical Components Targeting NLRP3 Inflammasome Activation

“…Although not present in natural sources used as foods, other diterpenoids, sesquiterpenes, iridoids, phytocannabinoids, and derivatives typical of plants used in Eastern and Western medicine, namely α-bisabolol, aucubin, abscisic acid (phytohormone), cannabidiol, phytanyl amine, triptolide, tanshinone IIA, sodium tanshinone IIA sulfonate, paclitaxel, phorbol myristate acetate, andrographolide, oridonin, glaucocalyxin A, and teuvincenone F have shown to be effective in the prevention of NLRP3 inflammasome activation by blocking the release of inflammasome enhancers, mainly IL-1β, IL-4, IL-6, IL-12, IL-18, caspase-1, and ROS [ 146 , 147 , 148 , 149 , 150 , 151 , 152 , 153 ]. Similarly, other terpenoids, such as the triterpenoid celastrol [ 154 ] and the sesquiterpenoids of Ainsliaea yunnanensis [ 155 ], have shown to be involved in the modulation of NLRP3.…”

Abscisic acid inhibited reactive oxygen species‐mediated endoplasmic reticulum stress by regulating the PPAR‐γ signaling pathway in ARDS mice

“…Due to the curative effects of ABA in many human diseases and a lack of adverse effects, ABA has attracted increasing attention. Recently, our coauthor found that ABA ameliorated OVA‐induced allergic airway inflammation (Zhao et al, 2021). Moreover, clinical results have shown that ABA is positively correlated with immune‐regulatory factors and negatively correlated with inflammatory markers in patients with chronic obstructive pulmonary disease (Hoang et al, 2021).…”

“…and then received 4 mg/kg LPS (Escherichia coli O111:B4, Sigma) in 50 μL of sterile saline intratracheally (i.t.). Based on previous findings (Hontecillas et al, 2013; Zhao et al, 2021), 100 mg/kg ABA (Sigma) was administered intraperitoneally for 7 days before LPS challenge, and another 100 mg/kg ABA was given 24 hr after LPS challenge in the same way. The mice were grouped randomly, n = 6 for each group.…”

Peroxisome Proliferator-Activated Receptors (PPARs) and Oxidative Stress in Physiological Conditions and in Cancer

“…In a similar way, the anti-inflammatory activity showed by abscisic acid, a natural phytohormone, in a murine model of allergic airway inflammation has been attributed to its ability in increasing PPARγ expression and, in consequence, in inhibiting NLRP3 [ 89 ]. In a mouse model of NAFLD (Nonalcoholic fatty liver disease), GW501516, a specific PPARβ/δ ligand, inhibited the activation of NLRP3, NLRP6, and NLRP10 and decreased the production of pro-inflammatory molecules induced by high fat diet and LPS [ 90 ].…”