Abstract
Effective therapies for stroke are still limited due to its complex pathological manifestations. QiShenYiQi (QSYQ), a component-based Chinese medicine capable of reducing organ injury caused by ischemia/reperfusion, may offer an alternative option for stroke treatment and post-stroke recovery. Recently, we reported a beneficial effect of QSYQ for acute stroke via modulation of the neuroinflammatory response. However, if QSYQ plays a role in subacute stroke remains unknown. The pharmacological action of QSYQ was investigated in experimental stroke rats which underwent 90 min ischemia and 8 days reperfusion in this study. Neurological and locomotive deficits, cerebral infarction, brain edema, and BBB integrity were assessed. TMT-based quantitative proteomics were performed to identify differentially expressed proteins following QSYQ treatment. Immunohistochemistry, western blot analysis, RT-qPCR, and ELISA were used to validate the proteomics data and to reveal the action mechanisms. Therapeutically, treatment with QSYQ (600 mg/kg) for 7 days significantly improved neurological recovery, attenuated infarct volume and brain edema, and alleviated BBB breakdown in the stroke rats. Bioinformatics analysis indicated that protein galectin-3 and its mediated inflammatory response was closely related to the beneficial effect of QSYQ. Specially, QSYQ (600 mg/kg) markedly downregulated the mRNA and protein expression levels of galectin-3, TNF-α, and IL-6 in CI/RI brain as well as serum levels of TNF-α and IL-6. Overall, our findings showed that the effective action of QSYQ against the subacute phase of CI/RI occurs partly via regulating galectin-3 mediated inflammatory reaction.
Highlights
Stroke is recognized as one of the main leading causes of death and serious long-term disability, as well as cognitive functional impairment, worldwide (Benjamin et al, 2019)
We have found the protective action of QSYQ against acute ischemic stroke via regulating neuroinflammatory network mobilization in a mouse model of cerebral ischemia and reperfusion (Wang et al, 2020)
Similar to Nim, the results indicated that treatment with QSYQ at middle (300 mg/kg) and high dose (600 mg/kg) markedly inhibited cerebral infarct volume as well as ameliorated neurological and behavioral impairment in subacute stroke rats (Figures 1–3), which revealed the beneficial effect of QSYQ on functional recovery
Summary
Stroke is recognized as one of the main leading causes of death and serious long-term disability, as well as cognitive functional impairment, worldwide (Benjamin et al, 2019). The standard clinical therapy for appropriate patients with acute ischemic stroke are tissue plasminogen activator (tPA)-mediated intravenous thrombolysis and executing intra-arterial thrombectomy to realize recanalization (Dong et al, 2017; Goda et al, 2020). Reperfusion injury following the restoration of blood supply may result in more adverse stroke outcomes via complicated pathological processes (Lin et al, 2016). It is believed that cerebral ischemia/reperfusion injury (CI/RI) has become an increasingly critical challenge for post-stroke recovery (Pan et al, 2007). It is crucial to discover novel and alternative therapies for ischemic stroke
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