Icaritin

Icaritin, a bioactive phytomolecule derived from Epimedium flavonoids (EFs), has been shown to have anti-inflammatory, anti-proliferative, and pro-apoptotic properties. However, its potential mechanisms in asthma airway inflammation have not been elucidated. In this study, Ovalbumin (OVA)-induced asthma mouse model and human bronchial epithelial cells (BEAS-2B) were used to illustrate the effects and mechanisms of Icaritin on airway inflammation. Specific airway resistance (sRAW) was used to detect the airway hyperresponsiveness (AHR). Hematoxylin-eosin (H&E) and periodic acid schiff (PAS) were used to detect the pathological changes. Bronchoalveolar lavage fluid (BALF) was used to detect the airway inflammatory cells. Serum and supernatants were used to detect the cytokines. Immunohistochemistry (IHC) and western blotting were used to detect the expression of TLR4, p-65, p-p65, IκBα, and p-IκBα. Cell Counting Kit-8 (CCK-8) was used to detect the cell viability. Icaritin suppressed AHR, attenuated eosinophilic infiltration and mucus hypersecretion, and significantly reduced the levels of OVA-specific cytokines in asthmatic mice. Moreover, Icaritin inhibited TLR4 expression, decreased phosphorylation of IκBα, and reduced NF-κB p65 activation in lung tissue of asthmatic mice. Further mechanistic studies showed that Icaritin reduces TLR4-induced inflammatory factor expression and blocks TLR4-activated NF-κB pathway in BEAS-2B cells. These findings demonstrate for the first time that Icaritin suppresses airway inflammation in asthma by inhibiting the TLR4/NF-κB pathway, suggesting its potential as a therapeutic agent for asthma.

Cerebral ischemic injury induces the polarization of astrocytes toward two different phenotypes, i.e., the proinflammatory A1 phenotype and the protective, anti-inflammatory A2 phenotype, affects the prognosis of cerebral ischemia. To explore the neuroprotective effect of phytoestrogens ICT on cerebral ischemic rehabilitation and the preliminary mechanism of regulating astrocyte polarization.

Transient middle cerebral artery occlusion (tMCAO)/reperfusion was performed on rats and then treated with ICT (i.p.) once daily for 28 days. Intervention of GPER specific inhibitor G15 was repeated. The body weight, Garcia JH scale, right/left brain weight ratio, CatWalk gait test and Y maze test to assess overall neural function in rats. Inflammatory factors in ischemic cortical were detected by Western blotting. The number of newborn neurons was observed by BrdU staining, and the double immunofluorescence staining and Western blotting to evaluated the activation and A1 and A2 polarization of astrocytes.

The results showed that ICT treatment markedly perfected functional outcomes on a long-term basis after ischemic stroke, it also improved learning and memory and gait. ICT inhibited the polarization of A1 type astrocytes and promoted the polarization of A2 type astrocytes, promote neuron regeneration in hippocampus DG region. G15 removes some of the protective effects of ICT.

The experimental results show that ICT exerts neuroprotective effects and regulates astrocyte polarization through GPER, suggesting that it may be a potential therapeutic agent for ischemic stroke during the recovery period.