BACKGROUND Piper nigrum L. (Piperaceae) is commonly used as a spice and traditional medicine in many countries. It has been reported to have anti-oxidant, anti-bacterial, anti-tumor, anti-mutagenic, anti-diabetic, and anti-inflammatory properties. However, the protective role of P. nigrum on epithelial function of upper respiratory tract injury in an allergic rhinitis (AR) mouse model has been unclear. This study aims to investigate the effects of P. nigrum fruit extract (PNE) on the nasal epithelial barrier function of the upper respiratory tract in an ovalbumin (OVA)-induced AR model. METHODS AR mouse model was established by intraperitoneal injection with 200 µL saline containing 50 µg OVA adsorbed to 1 mg aluminum hydroxide, and intranasal challenge with 20 µL per nostril of 1 mg/ml OVA. Besides, mice were orally administrated once daily with PNE and dexamethasone (Dex) in 13 days. The nasal symptoms, inflammatory cells, OVA-specific immunoglobulins, cytokines, nasal histopathology, and immunohistochemistry were evaluated. RESULTS The PNE oral administrations inhibited allergic responses via reduction of OVA-specific antibodies levels and mast cells histamine release, accordingly, the nasal symptoms in the early-phase reaction were also clearly ameliorated. In both nasal lavage fluid and nasal tissue, PNE suppressed the inflammatory cells accumulation, specifically with eosinophils. The intravenous Evans blue injection illustrated the epithelial permeability reduction of nasal mucosa layer in PNE-treated mice. Also; PNE treatments protected the epithelium integrity by preventing the epithelial shedding from nasal mucosa; as a result of enhancing the strong expression of the E-cadherin tight junction protein in cell-to-cell junctions, as well as inhibiting the degraded levels of zonula occludens-1 (ZO-1) and occludin into the nasal cavity. Additionally, PNE protected against nasal epithelial barrier dysfunction via enhancing the expression of Nrf2 activated form which led to increasing synthesis of the anti-inflammation enzyme HO-1. CONCLUSIONS These obtained results suggest that PNE has a promising strategy for epithelial barrier stabilization in allergic rhinitis treatment.

中文翻译：

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Piper Nigrum提取物通过激活Nrf2 / HO-1信号传导改善OVA诱导的鼻上皮屏障功能障碍。

背景技术在许多国家中，黑胡椒（Piperaceg L.（Piperaceae））通常被用作香料和传统药物。据报道具有抗氧化剂，抗细菌，抗肿瘤，抗诱变，抗糖尿病和抗炎特性。但是，在过敏性鼻炎（AR）小鼠模型中，黑假单胞菌对上呼吸道损伤的上皮功能的保护作用尚不清楚。这项研究旨在调查卵白蛋白（PNE）对卵清蛋白（OVA）诱导的AR模型中上呼吸道鼻粘膜上皮屏障功能的影响。方法通过腹腔注射200 µL含50 µg OVA的生理盐水（吸附于1 mg氢氧化铝）建立鼻腔动物模型，鼻腔注射1 mg / ml OVA的鼻孔20 µL建立AR小鼠模型。除了，在13天内，每天一次给小鼠口服PNE和地塞米松（Dex）。评估了鼻症状，炎症细胞，OVA特异性免疫球蛋白，细胞因子，鼻组织病理学和免疫组织化学。结果PNE口服给药通过降低OVA特异性抗体水平和肥大细胞组胺释放来抑制过敏反应，因此，早期反应中的鼻部症状也得到了明显改善。在鼻腔灌洗液和鼻腔组织中，PNE抑制炎症细胞的积累，特别是嗜酸性粒细胞。静脉内伊文思蓝注射液说明PNE治疗的小鼠鼻黏膜层上皮通透性降低。还; PNE治疗可通过防止鼻粘膜上皮脱落而保护上皮的完整性。由于增强了E-钙粘蛋白紧密连接蛋白在细胞间连接中的强表达，并抑制了小带闭合蛋白1（ZO-1）和闭合蛋白进入鼻腔的降解水平。此外，PNE通过增强Nrf2激活形式的表达来保护其免受鼻上皮屏障功能障碍的影响，从而导致抗炎酶HO-1的合成增加。结论这些获得的结果表明PNE在变应性鼻炎治疗中具有上皮屏障稳定化的有前途的策略。PNE通过增强Nrf2激活形式的表达来保护其免受鼻上皮屏障功能障碍的影响，从而导致抗炎酶HO-1的合成增加。结论这些获得的结果表明PNE在变应性鼻炎治疗中具有上皮屏障稳定化的有前途的策略。PNE通过增强Nrf2激活形式的表达来保护其免受鼻上皮屏障功能障碍的影响，从而导致抗炎酶HO-1的合成增加。结论这些获得的结果表明PNE在变应性鼻炎治疗中具有上皮屏障稳定化的有前途的策略。