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

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.

Phenolics-Rich Extracts of Dietary Plants as Regulators of Fructose Uptake in Caco-2 Cells via GLUT5 Involvement

“…Txnip, by forming a complex with GLUT5 and Rab11a, may promote the transporter trafficking to the apical membrane and enhance fructose uptake [ 52 ]. Furthermore, TXNIP has been described as a possible link between cellular redox state and metabolism [ 69 ] since it plays a pivotal role in the process of ROS production, inducing oxidative stress and inflammation. Mice treatment with resveratrol reduced ROS generation, which was accompanied by suppression of Txnip and an increase in superoxide dismutase (SOD) activity [ 69 ].…”

Oxidative Stress and Antioxidant Pathway in Allergic Rhinitis

“…For allergic rhinitis, the role of thioredoxin-interacting protein (TXNIP) was evaluated in oxidative stress [ 77 ]. In the ovalbumin (OVA)-induced allergic rhinitis murine model, expression of TXNIP in nasal mucosa, MDA level, and SOD activity were measured, along with allergic rhinitis markers such as nasal symptoms of sneezing and nasal rubbing, OVA-specific IgE and histamine in serum, and OVA-specific IgE, IL-4, IL-5, and tumor necrosis factor (TNF)-α in the nasal lavage fluid.…”

“…Therefore, current literature is somewhat limited in defining the complex and diverse molecular pathways of oxidative stress specific to allergic rhinitis. Recent studies which dealt with those dietary antioxidants in allergic rhinitis were reviewed, and the details, including the natural diet source of each antioxidant, are described in Table 1 [ 77 , 82 , 83 , 89 , 94 , 95 , 96 , 97 , 98 ].…”

“…As mentioned in the previous section, the allergic rhinitis animal model study showed the effectiveness of resveratrol in reducing oxidative stress markers such as MDA [ 77 ]. TXNIP level was positively correlated with MDA levels but negatively correlated with SOD activities, implying that resveratrol treatment might decrease TXNIP levels, leading to attenuation of oxidative stress.…”

Resveratrol Is a Natural Inhibitor of Human Intestinal Mast Cell Activation and Phosphorylation of Mitochondrial ERK1/2 and STAT3

“…Resveratrol (trans-3,4′,5 trihydroxystilbene, trans-Resveratrol) is mainly found in grapes, berries, or peanuts. In context of allergies, the polyphenolic compound was one amongst others that was able to prevent the development of a food allergy in mice [ 10 ], ameliorating the effects of atopic dermatitis and allergic rhinitis [ 11 , 12 ]. The anti-allergic and anti-inflammatory effects of resveratrol on different types of mast cell models have been shown previously [ 13 , 14 , 15 ].…”