Stroke ranks as the second leading trigger of mortality worldwide, which is an affliction of human beings (Surojit Paul (2021). Over the last three decades, China has seen a sharp rise in stroke deaths, surpassing other nations in this regard. Strokes can be classified into two primary categories: Ischemic and hemorrhagic strokes. The obstruction of a blood vessel that supplies a certain area of the brain is the cause of ischemic strokes, which account for approximately 75 %–85 % of all strokes. (Tuo et al., 2022). Patients who suffer an ischemic stroke may experience sudden paralysis, speech impairment, or vision loss because of blood flow obstruction brought on by thrombosis.(Moskowitz et al., 2010). Currently, there are two main interventions to restore blood flow: Pharmacological thrombolysis, which widely uses plasminogen activator in tissues, as well as mechanical thrombectomy. However, due to time constraints, several thrombolytic contraindications, and the possibility of intracerebral hemorrhage, half of the ischemic stroke patients failed to demonstrate any improvement (Leonard L L Yeo, 2013). Therefore, finding a new, effective treatment for ischemic stroke is essential.

According to recent studies (ingru Zhao et al., 2019; Liu et al., 2019), cerebral ischemia alters multiple miRNAs both in vitro and in vivo, demonstrating that miRNAs might serve as hub factors in the development of an ischemic stroke. Additionally, it has been demonstrated that microRNA-21 (miR-21) is a potent antiapoptotic and pro-survival agent in ischemia(Lopez et al., 2022).One of the most explored miRNAs is miR-21-5p.Its essential function is to carry out antiapoptotic effects and target a large number of genes engaged in endogenous and external apoptosis processes (Wang et al., 2021). A report from Wang revealed that miR-21 overexpression reduced TNF-α induced symptoms such as inflammation, oxidative stress, and cell death in interstitial cells of Cajal (Wang et al., 2020a, Wang et al., 2020b). According to Yan et al. (2021) by suppressing the p53/Bcl-2/Bax pathway, overexpression of miR-21 in vivo shrinks neuronal mortality, inhibits ischemia damage,as well as ameliorates neurological function. Lopez, MS et al. (2022)proved that raising miR-21 levels in brain tissue can reduce damage caused by a stroke and encourage the recovery of neurological function (Mary et al., 2022). These results imply that miR-21 promising treatment option for ischemic stroke and cerebral ischemia.

Kudiezi (KDZ) is a traditional Chinese medicine extracted and refined from Ixeris sonchifolia by water frying. It also contains complex chemical components, mainly flavonoids, sesquiterpene lactones, triterpene saponins, organic acids, amino acids, polysaccharides, and others (LI Ying et al., 2021). Pharmacological research has also revealed that flavonoids found in KDZ have neuroprotective effects on cell damage caused by ischemia and may be used to treat diseases caused by cerebral ischemia by improving the blood-brain barrier(BBB) following cerebral ischemia-reperfusion (I/R) damage (Yao-Chun Zhang et al., 2013). KDZ has a prominent role in expanding the cardiovascular system, increasing blood flow, protecting myocardial cells, and improving neural function defects (Fu-Qin Chen et al., 2016; Jae H Choi, 2018). In clinical practice, KDZ injection is frequently used to mitigate and cure myocardial ischemic diseases, including coronary atherosclerotic heart disease as well as angina pectoris (LI Ying et al., 2021). Previous clinical studies have found that KDZ has significant advantages for improving neural defects and motor function. (Xiaoqin Ye et al., 2011). Our previous study revealed that KDZ injection shields the brain against ischemia damage by inhibiting the TLR4/NF-κB signaling mechanism(Liu et al., 2017a, 2017b). KDZ inhibits the TLR4/NF-κB signaling pathway to prevent ischemia damage to the brain(Liu et al., 2017b). It was also identified that after acute cerebral ischemia, rats' nerve damage can be lessened by KDZ administration. The control of oxidative stress with antioxidant capability following brain ischemia could be a possible mechanisms(Liu et al., 2017a). The latest expert consensus on the clinical application of KDZ injection in 2019 believes that KDZ injection, which has a grade C quality of evidence and is highly recommended, can increase the overall effective rate of neurological impairment rating and the quality of daily life while treating acute cerebral infarction. (LIAO et al., 2019). So far, the neuroprotective mechanism of KDZ after I/R is ambiguous. This study's objective was to investigate the specific mechanism of KDZ in protecting the nervous system after I/R.