Thi Tho Bui1, Yanjing Fan2, Chun Hua Piao2, Thi Van Nguyen2, Dong-Uk Shin3, Sun Young Jung3, Eunjin Hyeon2, Chang Ho Song4, So-Young Lee3, Hee Soon Shin3, Ok Hee Chai5. 1. Faculty of Biology and Environmental Science, University of Science and Education, The University of Danang, Danang 59000, Viet Nam. 2. Department of Anatomy, Jeonbuk National University Medical School, Jeonju, Jeonbuk 54896, Republic of Korea. 3. Research Division of Food Functionality, Korea Food Research Institute, Wanju-gun, Jeonbuk 55365, Republic of Korea; KFRI School, Korea University of Science and Technology, Daejeon 305-350, Republic of Korea. 4. Department of Anatomy, Jeonbuk National University Medical School, Jeonju, Jeonbuk 54896, Republic of Korea; Institute for Medical Sciences, Jeonbuk National University, Jeonju, Jeonbuk 54896, Republic of Korea. 5. Department of Anatomy, Jeonbuk National University Medical School, Jeonju, Jeonbuk 54896, Republic of Korea; Institute for Medical Sciences, Jeonbuk National University, Jeonju, Jeonbuk 54896, Republic of Korea; Biomedical Research Institute, Jeonbuk National University Hospital, Jeonju, Jeonbuk 54896 Republic of Korea. Electronic address: okchai1004@jbnu.ac.kr.
Abstract
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.
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:ARmouse 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.
Authors: Murugappan Ramanathan; Anuj Tharakan; Venkataramana K Sidhaye; Andrew P Lane; Shyam Biswal; Nyall R London Journal: Laryngoscope Date: 2020-07-06 Impact factor: 3.325