Biomedicine & Pharmacotherapy (Sep 2022)
Qishen Yiqi Dropping Pill facilitates post-stroke recovery of motion and memory loss by modulating ICAM-1-mediated neuroinflammation
Abstract
Background: Promotion of functional recovery in patients is the primary goal of stroke management. However, its achievement is low due to the lack of full understanding of the complex pathological process of stroke and therefore limited therapeutic strategies. Qishen Yiqi Dropping Pill (QSYQ) is a component-based Chinese medicine that has been widely used in clinical treatment of ischemic cardiovascular diseases. Our previous studies indicated that QSYQ were protective for acute ischemic stroke in animal models and this study aimed to investigate the effect of QSYQ on brain function during stroke recovery. Methods: The therapeutic effects of QSYQ were evaluated by neurological deficit score, dark avoidance test, gait analysis, Morris water maze and brain tissue atrophy volume in a rat model of middle cerebral artery occlusion (MCAO) with ischemia for 60 min. The underlying mechanisms of QSYQ accelerating the functional recovery of MCAO rats was then revealed using proteomic sequencing and validated by immunohistochemistry, qRT-PCR and ELISA assays. The active components in QSYQ were elucidated by molecular docking and verified biochemically in vitro. Results: QSYQ treatment for 28 days significantly improved the neurological function, gait, spontaneous activity, spatial memory, and reduced brain atrophy in MCAO rats. Proteomic analysis of ischemic brain region and the following bioinformatics studies showed that QSYQ intervention markedly modulated neuroinflammatory responses post stroke, in which ICAM-1 played a dominant role. In particular, QSYQ reversed high cerebral expression of ICAM-1 in MCAO rats and decreased the content of TNF-α, IL-6 and IL1β in brain tissue and serum. In vitro, it was found that the active component rosmarinic acid in QSYQ evidently inhibit the expression of ICAM-1 caused by oxygen glucose deprivation/reoxygenation injury via using immunofluorescence staining. Conclusion: QSYQ effectively accelerates the recovery of motor impairment and memory loss in rats after stroke via downregulation of ICAM-1-mediated neuroinflammation, and rosmarinic acid is one of its main active components.
