Evaluating the Protective Properties of a Xyloglucan-Based Nasal Spray in a Mouse Model of Allergic Rhinitis.

A breached nasal epithelial barrier plays an important role in driving allergic rhinitis (AR). Corticosteroids remain the standard of care (SoC) but come with side effects, thus alternative safe and effective treatments able to avoid inflammation and restore barrier integrity are needed. The aim of the present study is to evaluate the barrier-forming capacity of a xyloglucan-based nasal spray (XG) and compare its efficacy to several SoC treatments (corticosteroid spray, oral mast-cell stabilizer and oral antihistamine) in reducing allergic responses in addition to its effect when concomitantly administered with an antihistamine. An ovalbumin (OVA)-induced mouse AR model was used. XG shows a significant efficacy in reducing histological damage in AR mice; improves nasal rubbing and histamine-induced hyper-responsiveness. Total and OVA-specific IgE as well as pro-inflammatory cytokines are significantly reduced compared to OVA challenged-mice, with im-proved efficacy when used as an add-on treatment. However, XG reduces mucous secreting cells (PAS-positive) and mucin mRNA expression similar to the corticosteroid-treated mice. XG-spray maintains tight junction protein expression (ZO-1) and conversely decreases HDAC1 significantly; the latter being highly expressed in AR patients. Moreover, the concomitant treatment showed in all of the endpoints a similar efficacy to the corticosteroids. This innovative approach may represent a novel therapeutic strategy for nasal respiratory diseases like AR, reducing undesirable side effects and improving the quality of life in patients.

Okra pectin relieves inflammatory response and protects damaged intestinal barrier in caerulein-induced acute pancreatic model.

BACKGROUND: Protecting the intestinal mucosa from being destroyed helps reduce the inflammation caused by acute pancreatitis (AP). In this study, whether okra pectin (OP) could attenuate the inflammation of AP through protecting the intestinal barrier was investigated. RESULTS: OP was obtained from crude okra pectin (COP) through the purification by DEAE cellulose 52 column. Supplementation with OP or COP in advance reduced the severity of AP, as revealed by lower serum amylase and lipase levels, abated pancreatic edema, attenuated myeloperoxidase activity and pancreas histology. OP or COP inhibited the production of pancreatic proinflammatory cytokines, including tumor necrosis factor-α and interleukin-6. In addition, the upregulation of AP-related proteins including ZO-1, occludin, the antibacterial peptide-defensin-1 (DEFB1) and cathelicidin-related antimicrobial peptide (CRAMP), as well as the histological examination of colon injuries, demonstrated that OP or COP provision could effectively maintain intestinal barrier function. Ultimately, dietary OP or COP supplementation could inhibit AP-induced intestinal inflammation. For the above, the effect of OP was better than COP. CONCLUSION: Dietary OP supplementation could be considered as a preventive method that effectively interferes with intestinal damage and attenuates inflammatory responses trigged by AP. © 2020 Society of Chemical Industry.

Calycosin alleviates allergic contact dermatitis by repairing epithelial tight junctions via down-regulating HIF-1α.

Calycosin, a bioactive component derived from Astragali Radix (AR; Huang Qi), has been shown to have an effect of anti-allergic dermatitis with unknown mechanism. This study aims to investigate the mechanism of calycosin related to tight junctions (TJs) and HIF-1α both in FITC-induced mice allergic contact dermatitis and in IL-1ß stimulated HaCaT keratinocytes. Th2 cytokines (IL-4, IL-5 and IL-13) were detected by ELISA. The epithelial TJ proteins (occludin, CLDN1 and ZO-1), initiative key cytokines (TSLP and IL-33) and HIF-1α were assessed by Western blot, real-time PCR, immunohistochemistry or immunofluorescence. Herein, we have demonstrated that allergic inflammation and the Th2 cytokines in ACD mice were reduced significantly by calycosin treatment. Meanwhile, calycosin obviously decreased the expression of HIF-1α and repaired TJs both in vivo and in vitro. In HaCaT keratinocytes, we noted that IL-1ß induced the deterioration of TJs, as well as the increased levels of TSLP and IL-33, which could be reversed by silencing HIF-1α. In addition, administration of 2-methoxyestradiolin (2-ME), a HIF-1α inhibitor,significantly repaired the TJs and alleviated the allergic inflammation in vivo. Furthermore, TJs were destroyed by DMOG or by overexpressing HIF-1α in HaCaT keratinocytes, and simultaneously, calycosin down-regulated the expression of HIF-1α and repaired the TJs in this process. These results revealed that calycosin may act as a potential anti-allergy and barrier-repair agent via regulating HIF-1α in AD and suggested that HIF-1α and TJs might be possible therapy targets for allergic dermatitis.

Granny Smith apple procyanidin extract upregulates tight junction protein expression and modulates oxidative stress and inflammation in lipopolysaccharide-induced Caco-2 cells.

The present work is undertaken to characterize a Granny Smith apple procyanidin extract (AE) and investigate the beneficial effect of the AE in the intestine in vitro. Each AE was characterized via LC-ESI-MS. Caco-2 cells were used to study the preventive actions of the AE against the downregulation of tight junction protein expression, oxidative stress and inflammation induced by lipopolysaccharides (LPS). Phenolic compounds present in the AE, including chlorogenic acid, catechin, epicatechin, proanthocyanidin dimers, and proanthocyanidin trimers, were characterized. The expression of the tight junction protein, including occludin and zona occludens (ZO)-1, increased significantly in LPS + AE treated Caco-2 cells, compared to LPS induced Caco-2 cells. Proanthocyanidin dimers had the most potent effect on increasing tight junction protein expression. The addition of LPS to Caco-2 cells induced oxidative stress and inflammation. However, incubation with proanthocyanidin dimers prevented LPS-mediated oxidative stress, including the increase of SOD, HO-1, CAT, and GSH-Px mRNA expression, and counteracted LPS-mediated inflammation as evidenced by the down-regulation of inflammatory markers (NF-κß, IL-6, and TNF-α mRNA expression). Our findings provide evidence that AE could upregulate tight junction protein expression, probably acting via the reduction of oxidative stress and inflammation.