Background: Icariin (ICA) is the major active ingredient extracted from Chinese herbal medicine Epimedium, which has the effects of improving cardiovascular function, inducing tumor cell differentiation and increasing bone formation. It is still rarely reported that ICA can exert its therapeutic potential in asthma via anti-airway remodeling. The point of the study was to estimate the role of ICA in anti-. airway remodeling and its possible mechanism of action in a mouse ovalbumin. (OVA)-induced asthma model. Methods: Hematoxylin and Eosin Staining were performed for measuring airway remodeling related indicators. ELISA, Western blot and Immunohistochemistr-. y (IHC) were used for analyzing the level of protein. RT-PCR was used for analyzing the level of mRNA. Results: On days 1 and 8, mice were sensitized to OVA by intraperitoneal injection. From day 16 to day 43, previously sensitized mice were exposed to OVA once daily by nebulizer. Interventions were performed orally with ICA (ICA low, medium and high dose groups) or dexamethasone 1 h prior to each OVA exposure. ICA improves pulmonary function, attenuates pulmonary inflammation and airway remodeling in mice exposed to OVA. Histological and Western blot analysis of the lungs show that ICA suppressed transforming growth factor beta 1 and vascular endothelial growth factor expression. Increase in interleukin 13 and endothelin-1 in serum and bronchoalveolar lavage fluid in OVA-induced asthmatic mice are also decreased by ICA. ICA attenuates airway smooth muscle cell proliferation, as well as key factors in the MAPK/Erk pathway. Conclusions: The fact that ICA can alleviate OVA-induced asthma at least partly through inhibition of ASMC proliferation via MAPK/Erk pathway provides a solid theoretical basis for ICA as a replacement therapy for asthma. These data reveal the underlying reasons of the use of ICA-rich herbs in Traditional Chinese Medicine to achieve good results in treating asthma.

Chronic obstructive pulmonary disease (COPD) is a worldwide epidemic. Current approaches are disappointing due to limited improvement of the disease development. The present study established 36‐week side stream cigarette smoke induced rat model of COPD with advanced stage feature and evaluted the effects of baicalin on the model. Fifty‐four Sprague–Dawley rats were randomly divided into six groups including room air control, cigarette smoke exposure, baicalin (40 mg/kg, 80 mg/kg, and 160 mg/kg), and budesonide used as a positive control. Rats were exposed to cigarette smoke from 3R4F research cigarettes. Pulmonary function was evaluated and pathological changes were also observed. Cytokine level related to airway inflammation and remodelling in blood serum, bronchoalveolar lavage fluid, and lung tissue was determined. Blood gases and HPA axis function were also examined, and antioxidant levels were quantified. Results showed that, after treatment with baicalin, lung function was improved and histopathological changes were ameliorated. Baicalin also regulated proinflammatory and anti‐inflammatory balance and also airway remodelling and anti‐airway remodelling factors in blood serum, bronchoalveolar lavage fluid, and lung tissue. Antioxidant capacity was also increased after treatment with baicalin in COPD rat model. HPA axis function was improved in baicalin treated groups as compared to model group. Therefore, baicalin exerts lung function protection, proinflammatory and anti‐inflammatory cytokine regulation, anti‐airway remodelling, and antioxidant role in long term CS induced COPD model.

CD4 ⁺ helper T (Th) cell subsets are critically involved in the pathogenesis of asthma. Naive Th cells differentiate into different subsets under the stimulation of different sets of cytokines, and the differentiation process is dominantly driven by lineage specific transcription factors, such as T-bet (Th1), GATA3 (Th2), RORγt (Th17) and Foxp3 (Treg). The differentiation mechanisms driven by these transcription factors are mutually exclusive, resulting in functional inhibition of these Th subsets to each other, particularly prominent between effector Th cells and Treg cells, such as Th2 versus Treg cells and Th17 versus Treg cells. Being of significance in maintaining immune homeostasis, the balance between effector Th cell response and Treg cell immunosuppression provides an immunological theoretical basis for us to understand the immunopathological mechanism and develop the therapy strategies of asthma. However, recent studies have found that certain factors involved in effector Th cells response, such as cytokines and master transcription factors (IL-12 and T-bet of Th1, IL-4 and GATA3 of Th2, IL-6 and RORγt of Th17), not only contribute to immune response of effector Th cells, but also promote the development and function of Treg cells, therefore bridging the interplay between effector Th cell immune responses and Treg cell immunosuppression. Although we have an abundant knowledge concerning the role of these cytokines and transcription factors in effector Th cell responses, our understanding on their role in Treg cell development and function is scattered thus need to be summarized. This review summarized the role of these cytokines and transcription factors involved in effector Th cell responses in the development and function of Treg cells, in the hope of providing new insights of understanding the immunopathological mechanism and seeking potential therapy strategies of asthma.

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.