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 inflammationrelated 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.

Epimedium Aqueous Extract Ameliorates Cerebral Ischemia/Reperfusion Injury through Inhibiting ROS/NLRP3-Mediated Pyroptosis

“…Therefore, efficacious agents to conquer CIRI should own potent antineuroinflammation and antioxidant activities. Previous research has found that the main active compounds of EA, namely ICA, ICS II, and ICT, can effectively penetrate the bloodbrain barrier and demonstrate potent anti-neuroinflammatory and antioxidant activities against multiple diseases [10,12,19,20]. The above-mentioned scenario and pharmacological properties of EP prompted us to excavate the therapeutic effect and its possible targets of EP on CIRI.…”

Acute Ischemic Stroke in Tubercular Meningitis Patients Without Conventional Vascular Risk Factors: A Retrospective Case Control Study

“…19 In addition to conventional vascular risk factors, such as hypertension, diabetes, long-term smoking and drinking and hyperlipidaemia, recent studies have found that inflammation is closely connected to cerebral infarction. [20][21][22] In clinical terms, tuberculosis is a common chronic inflammatory disease. Although tuberculosis meningitis comprises 1% of the incident cases of tuberculosis, it remains the most serious form of extrapulmonary tuberculosis.…”

Role of traditional Chinese medicine monomers in cerebral ischemia/reperfusion injury:a review of the mechanism

“…In a 2 h/22 h I/R rat model of MCAO, a dose of 200 mg/kg curcumin can reduce the expression of pro-inflammatory factors IL-6, TNF-α and iNOS by inhibiting the TLR4/p38/MAPK pathway, thereby inhibiting inflammatory response and improving brain injury and nerve function ( Huang et al, 2018 ). Icariin ( Zheng et al, 2022 ), diosgenin ( Zhang et al, 2022 ), and syringin ( Liu et al, 2022 ) administered in the MCAO rat model, improved brain injury and neurologic function by downregulating pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 to inhibit the inflammatory response.…”