Icariin inhibits the expression of IL-1β, IL-6 and TNF-α induced by OGD/R through the IRE1/XBP1s pathway in microglia

Context Icariin (ICA), a flavonol glycoside extracted from Epimedium brevicornum Maxim (Berberidaceae), has been proven to inhibit inflammatory response in ischaemic rats in our laboratory's previous work. However, its underlying mechanism is still unclear. Objective This study investigates the effects of ICA on endoplasmic reticulum (ER) stress mediated inflammation induced by cerebral ischaemia-reperfusion (I/R) injury in vitro. Materials and methods The primary cultured microglia were treated with oxygen-glucose deprivation (OGD) for 2 h followed by a 24 h reoxygenation. ICA (0.37, 0.74 and 1.48 mu mol/L) administration was performed 1 h prior OGD and acting through 2 h OGD. The control group was cultured in normal conditions. At 24 h after reoxygenation, the expression of IRE1 alpha, XBP1u, XBP1s, NLRP3 and caspase-1 was detected by western blotting (WB) and quantitative real-time (qRT) PCR; the expression of p-IRE1 alpha was examined by WB; the expression of IL-1 beta, IL-6 and TNF-alpha was measured by WB and enzyme-linked immunosorbent assay (ELISA). Results ICA (0.37, 0.74 and 1.48 mu mol/L) reduced the ratio of p-IRE1 alpha/IRE1 alpha, the mRNA level of IRE1 alpha, the expression of XBP1u, XBP1s, NLRP3, caspase-1 at both the mRNA and protein level expression of IL-1 beta, IL-6 and TNF-alpha in OGD/R injured microglia. Overexpression of IRE1 significantly reversed the effects of ICA. Discussion and conclusions These results suggested that ICA might decrease the expression of IL-1 beta, IL-6 and TNF-alpha by inhibiting IRE1/XBP1s pathway. The anti-inflammatory effect of ICA may provide a potential therapeutic strategy for the treatment of brain injury after stroke.

Automated summary

The study demonstrated that Icariin may reduce the expression of IL-1 beta, IL-6 and TNF-alpha by inhibiting the IRE1/XBP1s pathway, suggesting a potential therapeutic strategy for brain injury after stroke.