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Background Airborne pollutants, particularly exposure to particulate matter (PM), is a major risk factor for the development and exacerbation of respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD), and bronchitis. PM can penetrate the lower respiratory tract, disrupt epithelial barrier integrity, and promote the release of pro-inflammatory cytokines and chemokines, leading to persistent airway inflammation and structural remodeling. Recent research has focused on natural products for their potential applications in managing respiratory diseases. Atractylodes japonica rhizome has been shown to exert anti-inflammatory, anti-oxidant, mucolytic, and antibacterial effects, particularly in bronchitis and respiratory infections. Moreover, a fruit extract of Schisandra chinensis containing schisandrin (SZD) can effectively reduce lipopolysaccharide (LPS)-induced acute lung injury and cigarette smoke-induced COPD by reducing inflammatory cytokine production and oxidative stress. These findings provide a strong rationale for respiratory protective effects of CKD-F497, a standardized extract of the rhizome of A. japonica and the fruit of S. chinensis as a potential therapeutic agent for PM-induced airway inflammation. This study aimed to compare the chemical profiles of CKD-497 and CKD-F497 using qualitative analysis and to evaluate the respiratory protective effects of CKD-F497 in both in vitro and in vivo models of PM10- induced airway inflammation.
Methods CKD-F497 was obtained by extracting a 5:1 mixture of A. japonica rhizomes and S. chinensis fruits with 50% ethanol at low temperature, followed by concentration and drying. The extract was chemically characterized by highperformance liquid chromatography with diode-array detection (HPLC–DAD), confirming multiple constituents from CKD-F497. For in vivo assessment, a murine airway inflammation model was induced by intratracheal instillation of urban PM10 (200 ug per dose, administrated on days 0, 1, 7, 8, 14, and 15) in BALB/c mice. Mice were orally treated with CKD-F497 or vehicle control once daily for 21 days during the PM10 exposure period. On day 21, assessment was conducted including inflammatory cell infiltration in bronchoalveolar lavage fluid (BALF), measurement of proinflammatory cytokines, histopathological evaluation of lung injury and collagen deposition. For in vitro analysis, RAW 264.7 mouse macrophages were pretreated with CKD-F497 to stimulation with LPS, and inflammatory signaling was evaluated. NF-κB/MAPK pathway were analyzed by Western blot to anti-inflammatory effects of CKD-F497.
Results High-performance liquid chromatography–diode array detection analysis of CKD-497 and CKD-F497 extracts revealed highly similar chromatographic patterns, with nine major peaks including the key bioactive compounds 6(E),12(E)-tetradecadine-8,10-diyne-1,3-diol (TDD) and schisandrin (SZD) consistently detected in both extracts. The strong positive correlation in peak composition confirmed that CKD-F497 retains the chemical integrity and active constituents of the CKD-497, supporting their compositional equivalence. In addition, oral administration of CKD-F497 in a PM10-induced pulmonary inflammation mouse model effectively ameliorated airway inflammation, decreased immune cell infiltration in the BALF, lowered serum levels of pro-inflammatory cytokines, and ameliorated hispathological signs of lung injury and collagen deposition. Furthermore, in LPS-simulated RAW 264.7 mouse macrophage cell, CKD-F497 effectively inhibited LPS-mediated inflammatory response by deactivating NF-κB through suppression of the MAPK signaling pathway. These findings suggest that CKD-F497 is an effective option for treating airway inflammation and associated respiratory conditions.
Conclusion CKD-F497, extract from A. japonica and S. chinensis, exhibits potent anti-inflammatory and anti-fibrotic effects in a PM10-induced murine airway inflammation model and mitigates LPS-induced inflammatory activation in macrophages. These results highlight the therapeutic potentials of CKD-F497 for treating airway inflammation caused by air pollutants. CKD-F497 could serve as a functional supplement to protect against respiratory inflammatory diseases.*표시는 필수 입력사항입니다.
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