Anti-allergic and anti-inflammatory effects of resveratrol via inhibiting TXNIP-oxidative stress pathway in a mouse model of allergic rhinitis

World Allergy Organ J. 2020 Oct 22;13(10):100473. doi: 10.1016/j.waojou.2020.100473. eCollection 2020 Oct.

Abstract

Background: Allergic rhinitis (AR) is a type I hypersensitivity mediated by IgE in the nose. Thioredoxin-interacting protein (TXNIP) plays a pivotal role in the process of producing reactive oxygen species (ROS). Resveratrol is a TXNIP inhibitor. Nonetheless, its role and mechanism in AR are still undetermined. The present study aimed to explore the effect and mechanism of resveratrol on an ovalbumin (OVA) induced mouse model of AR.

Methods: AR murine model was established using OVA and administrated intranasally with resveratrol or N-acetylcysteine (NAC). Hematoxylin and eosin (HE) stain was used for evaluating eosinophils. Immunohistochemistry (IHC) staining and real-time PCR were employed to evaluate immunolabeling and mRNA expression of TXNIP in nasal mucosas of mice. Malondialdehyde (MDA) level and superoxide dismutase (SOD) activity in nasal tissue homogenates were measured using MDA and SOD Assay Kit. Concentrations of OVA-specific IgE and histamines in serum, and OVA-specific IgE, PGD2, LTC4, ECP, IL-4, IL-5, IL-6, IL-33 and TNF-α in nasal lavage fluid (NLF) were assayed by ELISA. In vitro studies, western blotting, real-time PCR, ELISA, ROS detecting dye DCFH-DA, MDA, and SOD Assay Kit were performed to evaluate the effects and mechanisms of OVA, resveratrol or NAC on spleen mononuclear cells.

Results: We found significant alternations of sneezing, nasal rubbing, inflammatory cytokines, eosinophil numbers, TXNIP, MDA, and SOD levels in resveratrol or NAC treated mice compared with untreated AR mice. In cultured spleen mononuclear cells, TXNIP, MDA, SOD, ROS and inflammatory cytokines levels were altered by OVA but reversed by resveratrol or NAC.

Conclusions: Resveratrol could effectively alleviate murine AR by inhibiting TXNIP-oxidative stress pathway.

Keywords: AR, Allergic rhinitis; Allergic rhinitis; ELISA, Enzyme-linked immunosorbent assay; IHC, Immunohistochemistry; MDA, Malondialdehyde; NAC, N-acetylcysteine; NLF, Nasal lavage fluid; OVA, Ovalbumin; Ovalbumin; Oxidative stress; ROS, Reactive oxygen species; Reactive oxygen species; Resveratrol; SOD, Superoxide dismutase; TXNIP; TXNIP, Thioredoxin-interacting protein; Th2, Type 2T helper.