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Saponin-enriched extract of Asparagus cochinchinensis alleviates airway inflammation and remodeling in ovalbumin-induced asthma model.

ABSTRACT: Asthma is a chronic inflammatory disease characterized by T-lymphocyte and eosinophil infiltration, mucus overproduction and airway hyper-responsiveness. The present study examined the therapeutic effects and action mechanism of a saponin-enriched extract of Asparagus cochinchinensis (SEAC) on airway inflammation and remodeling in an ovalbumin (OVA)-induced asthma model. To accomplish this, alterations of the nitric oxide (NO) level, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression levels, as well as variations in immune cell numbers, immunoglobulin E (IgE) concentration, histopathological structure and inflammatory cytokine levels were measured in lipopolysaccharide (LPS)-activated RAW264.7 cells or an OVA-induced mouse model of asthma treated with SEAC. The concentration of NO and mRNA levels of COX-2 and iNOS were significantly decreased in the SEAC + LPS-treated RAW264.7 cells compared with the vehicle + LPS-treated RAW264.7 cells. Additionally, in the OVA-induced asthma model, the number of immune cells in the bronchoalveolar lavage fluid, the concentration of OVA-specific IgE, the infiltration of inflammatory cells, the bronchial thickness and the levels of the inflammatory mediators interleukin-4 (IL-4), IL-13 and COX-2 were significantly lower in the OVA + SEAC?treated group compared with the OVA + vehicle?treated group. In addition, a significant reduction in goblet cell hyperplasia, peribronchiolar collagen layer thickness and VEGF expression for airway remodeling was detected in the OVA + SEAC?treated group compared with the OVA + vehicle?treated group. These findings indicate that SEAC is a suppressor of airway inflammation and remodeling, and may therefore be useful as an anti-inflammatory drug for the treatment of asthma.

SUBMITTER: Sung JE

PROVIDER: S-EPMC5627880 | biostudies-other | 2017 Sep

REPOSITORIES: biostudies-other

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Saponin-enriched extract of Asparagus cochinchinensis alleviates airway inflammation and remodeling in ovalbumin-induced asthma model.

Sung Ji-Eun JE Lee Hyun-Ah HA Kim Ji-Eun JE Yun Woo-Bin WB An Beum-Soo BS Yang Seung-Yun SY Kim Dong-Seob DS Lee Chung-Yeoul CY Lee Hee-Seob HS Bae Chang-Joon CJ Hwang Dae-Youn DY

International journal of molecular medicine 20170921 5

Asthma is a chronic inflammatory disease characterized by T-lymphocyte and eosinophil infiltration, mucus overproduction and airway hyper-responsiveness. The present study examined the therapeutic effects and action mechanism of a saponin-enriched extract of Asparagus cochinchinensis (SEAC) on airway inflammation and remodeling in an ovalbumin (OVA)-induced asthma model. To accomplish this, alterations of the nitric oxide (NO) level, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (C ...[more]

PMID: 28949387

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Project description:PurposeAirway remodeling is a critical feature of asthma. Secreted protein acidic and rich in cysteine (SPARC), which plays a cardinal role in regulating cell-matrix interactions, has been implicated in various fibrotic diseases. However, the effect of SPARC in asthma remains unknown.MethodsWe studied the expression of SPARC in human bronchial epithelial cells and serum of asthmatics as well as in the lung tissues of chronic asthma mice. The role of SPARC was examined by using a Lentivirus-mediated SPARC knockdown method in the ovalbumin (OVA)-induced asthma mice. The biological processes regulated by SPARC were identified using RNA sequencing. The function of SPARC in the remodeling process induced by transforming growth factor β1 (TGFβ1) was conducted by using SPARC small interfering RNA (siRNA) or recombinant human SPARC protein in 16HBE cells.ResultsWe observed that SPARC was up-regulated in human bronchial epithelia of asthmatics and the asthmatic mice. The levels of serum SPARC in asthmatics were also elevated and negatively correlated with the forced expiratory volume in one second (FEV1) to forced vital capacity ratio (FVC) (r = -0.485, P < 0.01) and FEV1 (%predicted) (r = -0.425, P = 0.001). In the chronic asthmatic mice, Lentivirus-mediated SPARC knockdown significantly decreased airway remodeling and airway hyper-responsiveness. According to gene set enrichment analysis, negatively enriched pathways found in the OVA + short hairpin-SPARC group included ECM organization and collagen formation. In the lung function studies, knockdown of SPARC by siRNA reduced the expression of remodeling-associated biomarkers, cell migration, and contraction by blocking the TGFβ1/Smad2 pathway. Addition of human recombinant SPARC protein promoted the TGFβ1-induced remodeling process, cell migration, and contraction in 16HBE cells via the TGFβ1/Smad2 pathway.ConclusionsOur studies provided evidence for the involvement of SPARC in the airway remodeling of asthma via the TGFβ1/Smad2 pathway.

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Saponin-enriched extract of Asparagus cochinchinensis alleviates airway inflammation and remodeling in ovalbumin-induced asthma model.

Publications

Saponin-enriched extract of Asparagus cochinchinensis alleviates airway inflammation and remodeling in ovalbumin-induced asthma model.

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