Abstract
Icariin is a main component of the Chinese medicinal plant Epimedium brevicornu Maxim, exhibits potent activity against inflammatory diseases. Our previous data demonstrated the valid bioactivity of icariin on mitigating rodent asthma. Endoplasmic reticulum (ER) stress and nuclear factor-κB (NF-κB) pathway were involved in the pathogenesis of asthma. However, it remains poorly defined that whether icariin could inhibit ER stress and NF-κB mediated apoptosis in asthma and further influence the central neural system. Herein, we investigated the effects of icariin on primary cultured fetal rat hippocampal neurons and OVALPS-OVA induced asthma rat model. Asthma rat models were established by ovalbumin (OVA) and lipopolysaccharide (LPS) intraperitoneal injection and OVA inhalational challenge. Airway resistance was analyzed to evaluate lung function after last challenge and pathological changes were detected on lung tissues. Assessment of inflammatory cells counts in bronchoalveolar lavage fluids (BALF) were performed and ELISA was used to determine levels of interleukin (IL)-1β, tumor necrosis factor-α, IL-6, and interferon-γ in serum. Protein expression of BiP and IRE-1α, XBP-1s and phosphorylation-IκBα (p-IκBα), IκBα, and p65 as well as cytochrome c, caspase-3 (cleaved caspase-3), and caspase-9 (cleaved caspase-9) were tested by Western blot. We found that icariin could remarkably improve pulmonary function and reduce inflammatory cells in the lung, levels of inflammatory cytokines, and ER stress related proteins as well as NF-κB were prominently suppressed by icariin. Our results suggested that icariin had an inhibitory effect on airway inflammation and neuroprotective effect on ER stress and NF-κB mediated apoptosis in asthma rats and cultured fetal rat hippocampal neurons, which may provide new mechanistic insights into the asthma prevention and treatment of icariin.
Highlights
Asthma is believed to be a most common respiratory disorder threatening hundreds of millions individuals worldwide, and the prevalence has increased considerably over the past decades
The results showed that BiP level significantly increased in a dose-dependent manner in primary cultured rat hippocampal neurons pretreated with icariin compared to that
Mounting evidence had indicated that neutrophils could mediate severe and fatal asthma (Lamblin et al, 1998; Tsokos and Paulsen, 2002; Mauad and Dolhnikoff, 2008), and current asthma treatment guidelines are based predominantly on the T helper type 2 phenotype, and better treatment for severe asthma patients was comprised by the primary unmet needs of current therapies
Summary
Asthma is believed to be a most common respiratory disorder threatening hundreds of millions individuals worldwide, and the prevalence has increased considerably over the past decades. As a defining feature of the stress response (BuskeKirschbaum, 2009), activation of the hypothalamic-pituitaryadrenal (HPA) axis has been demonstrated to be strongly associated with asthma pathogenesis (Wei et al, 2017), and corticotropin releasing hormone (CRH) that secreted by the hypothalamus plays a central role in this activation. Recent studies suggested that hippocampus was a high regulation center of the HPA axis in the limbic system, and a sensitive area of stress injury, and CRH may lead to stress-induced hippocampal dysfunction (Lyons et al, 1991; Brunson et al, 2001; Ivy et al, 2010). The underlying mechanism has not been well elucidated and an effective treatment is still insufficient
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