Effects of icariin on cell injury and glucocorticoid resistance in BEAS‑2B cells exposed to cigarette smoke extract

Abstract

Glucocorticoids (GCs) exert a therapeutic effect in numerous chronic inflammatory diseases. However, chronic obstructive pulmonary disease (COPD) tends to be GC-resistant. Icariin, a major component of flavonoids isolated from Epimedium brevicornum Maxim (Berberidaceae), significantly relieves symptoms in patients with COPD. However, the mechanism of action remains unclear and further investigation is required to establish whether it may serve as an alternative or complementary therapy for COPD. The aim of the present study was to determine the effects of icariin in human bronchial epithelial cells exposed to cigarette smoke extract (CSE) and to determine whether icariin reverses GC resistance. The results revealed that icariin significantly increased the proliferation of CSE-exposed cells. Furthermore, icariin significantly increased protein expression of the anti-inflammatory factor interleukin (IL)-10 and significantly decreased protein expression of the pro-inflammatory factors IL-8 and tumor necrosis factor α. Icariin also attenuated the expression of the cellular matrix remodelling biomarkers matrix metallopeptidase 9 and tissue inhibitor of metalloproteinase 1, and decreased the production of reactive oxygen species (ROS). In addition, icariin regulated the expression of GC resistance-related factors, such as GC receptors, histone deacetylase 2, nuclear factor erythroid-2-related factor 2 and nuclear factor κ B. The results obtained in the present study suggested that icariin may decrease CSE-induced inflammation, airway remodelling and ROS production by mitigating GC resistance. In conclusion, icariin may potentially be used in combination with GCs to increase therapeutic efficacy and reduce GC resistance in COPD.

Tiao‐Bu‐Fei‐Shen Formula Improves Glucocorticoid Resistance of Chronic Obstructive Pulmonary Disease via Downregulating the PI3K‐Akt Signaling Pathway and Promoting GRα Expression

“…Zhang et al showed that baicalin ameliorated CS-induced airway inflammation in rats by enhancing HDAC2 protein expression and inhibiting the expression of NF- κ B and its downstream target PAI-1 [ 41 ]. Hu et al not only showed that icariin reduced CSE-induced inflammation, airway remodeling, and ROS production but also reported that treatment with the combination of icariin and glucocorticoids could reduce glucocorticoid resistance [ 42 ]. Although TCM has proved to be successful in improving glucocorticoid resistance in COPD, whether the underlying mechanism involves downregulation of PI3K β /AKT signaling and upregulation of HDAC2 expression remains unclear.…”

Network Pharmacology and Experimental Validation to Reveal Effects and Mechanisms of Icariin Combined with Nobiletin against Chronic Obstructive Pulmonary Diseases

“…It has been reported that icariin inhibits CSE-induced inflammation, ROS production, and airway remodeling via mitigating glucocorticoids resistance in CSE-exposed BEAS-2B cells [ 35 ]. In addition, nobiletin exhibited protective effects in decreasing the production of TNF- α , IL-6 via restraining activation of NF- κ B signaling in the LPS-induced acute lung injury mice model and LPS-stimulated A549 cells [ 36 ].…”

Comparative Effectiveness and Safety of Seven Qi-Tonifying Chinese Medicine Injections for AECOPD Patients: A Systematic Review and Network Meta-Analysis

“…It is reported that icariin can not only increase expression of the anti-inflammatory factor interleukin-10 but also decrease expression of various proinflammatory factors IL-8 and tumor necrosis factor- α . Besides this, icariin can regulate the expression of Glucocorticoids (GC) resistance-related factors, which was beneficial for reversing GC resistance in COPD [ 69 , 70 ]. Regarding the administration ways, intravenous mode was the preferred mode of administration (6 studies), followed by intermuscular administration (1 study).…”