Icariin attenuates ischaemic stroke through suppressing inflammation mediated by endoplasmic reticulum stress signalling pathway in rats

Abstract Ischaemic stroke possesses the characteristics of high incidence, high disability and high mortality. Icariin (ICA) is a flavonoid extracted from the traditional Chinese medicine Epimedium . The protective effect of ICA on ischaemic stroke is worthy of further study. In this study, male Sprague–Dawley rats were randomly divided into the following seven groups: sham, model, ICA low‐dose (10 mg/kg), ICA medium‐dose (20 mg/kg), ICA high‐dose (40 mg/kg), positive control drug (12 mg/kg nimodipine) and endoplasmic reticulum stress induction (0.16 mg/kg tunicamycin) groups. The model of cerebral ischaemia–reperfusion injury in the rats, including 2 h ischaemia and 24 h reperfusion, was accomplished by applying the method of transient middle cerebral artery occlusion (MCAO). At 24 h reperfusion, neurological deficits, brain water content, pathological damage of brain tissues, the expression of inflammation‐related targets, and the signal pathway‐related proteins were explored. Compared with the model group, ICA significantly improved neurological deficits, brain oedema and pathological damage after MCAO. In addition, ICA increased neuron survival, reduced microglial activation and expression of IL‐1β, alleviating the inflammatory damage caused by ischaemic stroke. Moreover, ICA suppressed the expressions of glucose‐regulated protein 78 (GRP78), inositol requiring enzyme‐1 α (IRE1α), phospho‐IRE1α (p‐IRE1α), protein kinase RNA‐like ER kinase (PERK), phospho‐PERK (p‐PERK), spliced XBP1 (XBP1s), unspliced XBP1 (XBP1u), thioredoxin‐interacting protein (TXNIP), NLRP3, and caspase‐1. These results suggested that ICA offers neuroprotection against ischaemic stroke by inhibiting ER stress‐mediated inflammation.