The protective role of Piper nigrum fruit extract in an ovalbumin-induced allergic rhinitis by targeting of NFκBp65 and STAT3 signalings.

Piper nigrum L. is commonly used as a traditional medicine and food 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 effect of P. nigrum on allergic rhinitis (AR) has been unclear. In the present study, an OVA-induced AR mice model were established to investigate the anti-allergic, anti-inflammation properties of P. nigrum fruit extract (PNE). Oral administrations of PNE inhibited the allergic nasal symptoms including rubbing and sneezing in the early-phage of AR. In both NALF and nasal tissue, PNE suppressed the inflammatory cells accumulation, specifically with eosinophils in NALF. Additionally, PNE prevented the activation of STAT3 and NFκBp65 signaling in the cytoplasm which led to increasing the synthesis of the anti-inflammatory Th1 cytokines and suppressing the inflammatory Th2, Th17 cytokines. These obtained results suggest that PNE has the promising strategy for immunotherapy in allergic rhinitis disease.

Bui TT ，Piao CH ，Hyeon E ，Fan Y ，Van Nguyen T ，Jung SY ，Choi DW ，Lee SY ，Shin HS ，Song CH ，Chai OH ... -  《-》

Piper Nigrum extract improves OVA-induced nasal epithelial barrier dysfunction via activating Nrf2/HO-1 signaling.

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. 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. 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. These obtained results suggest that PNE has a promising strategy for epithelial barrier stabilization in allergic rhinitis treatment.

Bui TT ，Fan Y ，Piao CH ，Nguyen TV ，Shin DU ，Jung SY ，Hyeon E ，Song CH ，Lee SY ，Shin HS ，Chai OH ... -  《-》

Saikosaponin A ameliorates nasal inflammation by suppressing IL-6/ROR-γt/STAT3/IL-17/NF-κB pathway in OVA-induced allergic rhinitis.

Allergic rhinitis (AR) is a type I hypersensitivity immune response and is a common chronic allergic respiratory disorder characterized by one or more nasal symptoms. Despite many studies on AR therapy, the drugs of treatment for AR remain limited in effect. In the present study, we aimed to elucidate the effects of saikosaponin A (SSA) on nasal inflammation, T helper (Th)2 and Th17 cytokines, retinoic acid-related orphan nuclear receptor (ROR)-γt, signal transducer and activator of transcription (STAT)3, and nuclear factor (NF)-κB signalings in ovalbumin (OVA)-induced AR mice model. OVA-induced AR mice exhibited increase in nasal symptoms, histological alteration, OVA-specific immunoglobulin (Ig)E/IgG1, ROR-γt, STAT3 and NF-κB signalings. However, the administration of SSA significantly decreased allergic symptoms including nasal rubbing and sneezing. Additionally, histological alterations such as mucosa layer thickness, goblet cell hyperplasia, eosinophils and mast cell infiltration in nasal tissues dramatically improved by treatment with SSA. Also, SSA treatment decreased the levels of OVA-specific IgE/IgG1 in serum and the levels of Th2 and Th17 cytokines such as interleukin (IL)-6 and IL-17 in nasal lavage fluid (NALF). Moreover, SSA inhibited the activation of transcription factor ROR-γt, STAT3 and phosphorylated STAT3 in both NALF and lung. Futher, SSA could also significantly inhibit the expressions of NF-κB p65 and phosphorylated NF-κB p65 in NALF and lung. These present results suggested that SSA may attenuate OVA-induced allergic rhinitis through regulating the expression of IL-6/ROR-γt/STAT3/IL-17/NF-κB signaling. The results indicate that SSA may be used as a therapeutic candidate for allergic rhinitis disease.

Piao CH ，Song CH ，Lee EJ ，Chai OH ... -  《-》

Piper nigrum extract ameliorated allergic inflammation through inhibiting Th2/Th17 responses and mast cells activation.

Piper nigrum (Piperaceae) is commonly used as a spice and traditional medicine in many countries. P. nigrum has been reported to have anti-oxidant, anti-bacterial, anti-tumor, anti-mutagenic, anti-diabetic, and anti-inflammatory properties. However, the effect of P. nigrum on allergic asthma has not been known. This study investigated the effect of P. nigrum ethanol extracts (PNE) on airway inflammation in asthmatic mice model. In the ovalbumin (OVA)-induced allergic asthma model, we analysed the number of inflammatory cells and cytokines production in bronchoalveolar lavage fluid (BALF) and lung tissue; histological structure; as well as the total immunoglobulin (Ig)E, anti-OVA IgE, anti-OVA IgG1 and histamine levels in serum. The oral administration (200 mg/kg) of PNE reduced the accumulation of inflammatory cells (eosinophils, neutrophils in BALF and mast cells in lung tissue); regulated the balance of the cytokines production of Th1, Th2, Th17 and Treg cells, specifically, inhibited the expressions of GATA3, IL-4, IL-6, IL-1β, RORγt, IL-17A, TNF-α and increased the secretions of IL-10, INF-γ in BALF and lung homogenate. Moreover, PNE suppressed the levels of total IgE, anti-OVA IgE, anti-OVA IgG1 and histamine release in serum. The histological analysis showed that the fibrosis and infiltration of inflammatory cells were also ameliorated in PNE treated mice. On the other hand, PNE inhibited the allergic responses via inactivation of rat peritoneal mast cells degranulation. These results suggest that PNE has therapeutic potential for treating allergic asthma through inhibiting Th2/Th17 responses and mast cells activation.

Bui TT ，Piao CH ，Song CH ，Shin HS ，Shon DH ，Chai OH ... -  《-》

The Immuno-Modulatory Activities of Pentaherbs Formula on Ovalbumin-Induced Allergic Rhinitis Mice via the Activation of Th1 and Treg Cells and Inhibition of Th2 and Th17 Cells.

Li P ，Tsang MS ，Kan LL ，Hou T ，Hon SS ，Chan BC ，Chu IM ，Lam CW ，Leung PC ，Wong CK ... -  《MOLECULES》