Abstract
Casticin has been isolated from Vitex trifolia and found to have anti-inflammatory and anti-tumor properties. We also previously discovered that casticin can reduce pro-inflammatory cytokines and ICAM-1 expression in inflammatory pulmonary epithelial cells. In the present study, we evaluated whether casticin reduced airway hyper-responsiveness (AHR), airway inflammation, and oxidative stress in the lungs of a murine asthma model and alleviated inflammatory and oxidative responses in tracheal epithelial cells. Female BALB/c mice were randomly divided into five groups: normal controls, ovalbumin (OVA)-induced asthma, and OVA-induced asthma treated with intraperitoneal injection of casticin (5 or 10 mg/kg) or prednisolone (5 mg/kg). Casticin reduced AHR, goblet cell hyperplasia, and oxidative responses in the lungs of mice with asthma. Mechanistic studies revealed that casticin attenuated the levels of Th2 cytokine in bronchoalveolar lavage fluids and regulated the expression of Th2 cytokine and chemokine genes in the lung. Casticin also significantly regulated oxidative stress and reduced inflammation in the lungs of mice with asthma. Consequently, inflammatory tracheal epithelial BEAS-2B cells treated with casticin had significantly suppressed levels of pro-inflammatory cytokines and eotaxin, and reduced THP-1 monocyte cell adherence to BEAS-2B cells via suppressed ICAM-1 expression. Thus, casticin is a powerful immunomodulator, ameliorating pathological changes by suppressing Th2 cytokine expression in mice with asthma.
Highlights
Asthma is a common allergic and inflammatory disease of the respiratory system
We previously found that casticin can reduce pro-inflammatory cytokine and intercellular adhesion molecule 1 (ICAM-1) expression by blocking the NF-κB, MAPK, and PI3K/Akt pathways in IL-1β-activated A549 human lung epithelial cells (Liou et al, 2014; Liou and Huang, 2017)
We found that a high inhaled dose of methacholine (40 mg/ml) in casticin or prednisolone-treated mice with asthma significantly decreased the Penh values compared to the OVA
Summary
Asthma is a common allergic and inflammatory disease of the respiratory system. During an acute asthma attack, smooth muscle contraction exaggerates airway narrowing, and allergystimulated respiratory epithelial cells induce excess mucus secretion to block airways, resulting in breathing difficulties and potentially even suffocation (Lambrecht and Hammad, 2012). Recent studies have confirmed immune system imbalance as one of the important factors in allergic asthma (Duong et al, 2015). In asthma patients, activated Th2 cells release excess cytokines to stimulate airway hyper-responsiveness (AHR) and induce eosinophil infiltration, resulting in exacerbated inflammation and allergic reaction in the lungs (Parulekar et al, 2016). Th2-associated cytokines induce goblet cell hyperplasia and mucus secretion, causing severe respiratory obstruction, and irritated oxidative responses that contribute to lung damage in mice with asthma. Regulating the immune system and attenuating the improper activation of Th2 cells is important for the amelioration of asthma (Steinke and Lawrence, 2014)
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