PRDX1 Interfering Peptide Disrupts Amino Acids 70-90 of PRDX1 to Inhibit the TLR4/NF-κB Signaling Pathway and Attenuate Neuroinflammation and Ischemic Brain Injury.

Ischemic stroke ranks among the leading causes of death and disability in humans and is accompanied by motor and cognitive impairment. However, the precise mechanisms underlying injury after stroke and effective treatment strategies require further investigation. Peroxiredoxin-1 (PRDX1) triggers an extensive inflammatory cascade that plays a pivotal role in the pathology of ischemic stroke, resulting in severe brain damage from activated microglia. In the present study, we used molecular dynamics simulation and nuclear magnetic resonance to detect the interaction between PRDX1 and a specific interfering peptide. We used behavioral, morphological, and molecular experimental methods to demonstrate the effect of PRDX1-peptide on cerebral ischemia-reperfusion (I/R) in mice and to investigate the related mechanism. We found that PRDX1-peptide bound specifically to PRDX1 and improved motor and cognitive functions in I/R mice. In addition, pretreatment with PRDX1-peptide reduced the infarct area and decreased the number of apoptotic cells in the penumbra. Furthermore, PRDX1-peptide inhibited microglial activation and downregulated proinflammatory cytokines including IL-1ß, IL-6, and TNF-α through inhibition of the TLR4/NF-κB signaling pathway, thereby attenuating ischemic brain injury. Our findings clarify the precise mechanism underlying PRDX1-induced inflammation after ischemic stroke and suggest that the PRDX1-peptide can significantly alleviate the postischemic inflammatory response by interfering with PRDX1 amino acids 70-90 and thereby inhibiting the TLR4/NF-κB signaling pathway. Our study provides a theoretical basis for a new therapeutic strategy to treat ischemic stroke.

[Efficacy assessment of treating post-stroke shoulder-hand syndrome patients of yin deficiency yang hyperactivity with blood stasis stagnation collaterals syndrome by yishen tongluo decoction].

OBJECTIVE: To assess the efficacy of Yishen Jiejing Decoction (YJD) in treating poststroke shoulder-hand syndrome (SHS) patients of yin deficiency yang hyperactivity with blood stasis stagnation collaterals syndrome. METHODS: Totally 60 SHS patients of yin deficiency yang hyperactivity with blood stasis stagnation collaterals syndrome were randomly assigned to two groups, the treatment group and the control group, 30 cases in each group. Conventional rehabilitation training and therapeutics were applied in all patients. Besides, patients in the treatment group took 50 mL YJD, twice a day. One month without interruption consisted of one course of treatment. The curative effects of each group were evaluated respectively before treatment and at one month after treatment. The neurologic impairment, TCM syndrome, and the improvement of upper limbs movement were assessed by the neurologic impairment integral, scoring for TCM syndrome diagnostics, Fugl-Meyer Assessment (U-FMA). Adverse reactions were observed at the same time. RESULTS: The effective rate of stroke was 86.67% and the effective rate of SHS was 90.00% in the treatment group, higher than those of the control group (P < 0.05). Both groups got improvement in neurologic impairment, stroke induced blood stasis syndrome, yin deficiency yang hyperactivity syndrome, and the improvement of upper limbs movement after treatment (all P < 0.05). Besides, all the improvement was obviously superior in the treatment group (P < 0. 05). No adverse reaction occurred during the course of treatment. CONCLUSION: The curative effect of YJD combined with conventional rehabilitation training was confirmative and superior to the control group.