AUTHOR=Kim Hyejeong , Choi Jihye , Seo Jaeok , Lim Hyungjoon , Kang Sung Kwon 

TITLE=CKD-497 inhibits NF-kB signaling and ameliorates inflammation and pulmonary fibrosis in ovalbumin-induced asthma and particulate matter-induced airway inflammatory diseases

JOURNAL=Frontiers in Pharmacology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1428567

DOI=10.3389/fphar.2024.1428567

ISSN=1663-9812

ABSTRACT=<p><bold>Introduction:</bold> Air pollution, allergens, and bacterial infections are major contributors to pathological respiratory disorders worldwide. CKD-497, derived from the rhizome of <italic>Atractylodes japonica</italic> and the fruits of <italic>Schisandra chinensis</italic>, is known for its ability to relieve cough and facilitate phlegm expectoration. However, its protective action against allergic asthma and fine dust-induced lung inflammation, along with its underlying mechanisms, have not been thoroughly investigated.</p><p><bold>Methods:</bold> In this study, we established mouse models of ovalbumin (OVA)-induced asthma and particulate matter (PM)-induced pulmonary inflammation to evaluate the effects of CKD-497. Mice were administered CKD-497 orally, and various parameters such as airway inflammation, mucus production, and proinflammatory cytokine levels (IL-1β, IL-6, TNF-α) were measured. Additionally, the macrophage cell line RAW264.7 was pretreated with CKD-497 and stimulated with lipopolysaccharide (LPS) to assess inflammation via the NF-kB signaling pathway.</p><p><bold>Results:</bold> Oral administration of CKD-497 effectively attenuated airway inflammation and mucus production in both OVA-induced asthma and PM-induced lung inflammation models. It also significantly decreased the production of proinflammatory cytokines IL-1β, IL-6, and TNF-α. CKD-497 alleviated leukocyte infiltration, including neutrophils, and reduced fibrillary collagen deposition in PM<sub>10</sub>-treated mice. <italic>In vitro</italic>, CKD-497 pretreatment inhibited LPS-induced inflammation in RAW264.7 cells through the suppression of the NF-kB signaling pathway.</p><p><bold>Discussion:</bold> CKD-497 shows potent anti-inflammatory effects in mouse models of asthma and PM-induced lung inflammation, potentially mediated by the inhibition of the NF-kB pathway. These findings suggest that CKD-497 could serve as a functional supplement to protect against respiratory diseases by mitigating pulmonary and airway inflammation induced by allergens and air pollution.</p>