Anticerebral Ischemia-Reperfusion Injury Activity of Synthesized Puerarin Derivatives

Abstract

When cerebral ischemia-reperfusion injury happened in patients, multiple pathological processes occur, such as leukocyte infiltration, platelet, and complement activation, which would result in cognitive dysfunction and inflammation. Puerarin has shown protective effect on injury of neural cell. In order to enhance this protective effect of puerarin, puerarin derivatives with different log⁡P values were designed and synthesized. The original phenolic hydroxyl in the puerarin molecules was substituted in order to change the blood-brain barrier permeability and thus enhance the efficacy for preventing cerebral ischemia/reperfusion injury. And the structure of the newly synthesized molecules was confirmed by 1H NMR spectroscopy and mass spectrometry. The mouse model of cerebral artery ischemia/reperfusion injury was established to test the anticerebral ischemia-reperfusion injury activity of the puerarin derivatives. The assays of the water maze, Y maze, brain cortex Ca2+-Mg2+-ATP enzyme, and iNOS enzyme activity were performed in this mouse model. The results showed that puerarin derivative P1-EA and P2-EA were resulting in an increased lipophilicity that enabled the derivatives to pass more efficiently through the blood-brain barrier, thus, improving the protective effects against cerebral ischemia/reperfusion injury. Therefore, derivatives of puerarin may serve as promising approach to improve neuron function in ischemia-reperfusion brain injury-related disorders.

Platelet function-guided modification in antiplatelet therapy after acute ischemic stroke is associated with clinical outcomes in patients with aspirin nonresponse

“…The prevalence of aspirin nonresponse was 27.5% in present study, and was similar to the prevalence reported in our previous studies [ 8 , 11 , 21 ] and some other studies [ 9 , 22 ]. A recent systematic review and meta-analysis showed that the prevalence of high on-treatment of platelet reactivity (HTPR) on aspirin was 23% (95% CI: 20–28%), and the patients with HTPR had a significantly higher risk for ischemic stroke recurrence (relative risk = 1.81, 95% CI: 1.30–2.52; P < 0.001) [ 23 ].…”

“…The finding is consistent with our present study. The mechanisms associated with aspirin nonresponse are complex and mutilfactorial, such as noncompliance, diabetes mellitus, reduced absorption, the biosynthesis of thromboxane A2 from pathways not inhibited by aspirin as well as alternative pathways involved in platelet activation not blocked by aspirin [ 9 , 11 , 21 , 22 ]. In present study, our results also showed that the diabetes mellitus was associated with aspirin nonresponse.…”

Puerarin attenuates locomotor and cognitive deficits as well as hippocampal neuronal injury through the PI3K/Akt1/GSK-3β signaling pathway in an in vivo model of cerebral ischemia

“…Puerarin–one of the active ingredients in herbal medicine–has protective functions in multiple tissues, such as bone, liver, the cardiovascular system and the brain [ 6 ]. Studies have demonstrated that in rats with cerebral I/R injury, puerarin enhanced antioxidant capacity, removed lipid peroxidation products, improved antioxidant activity, and reduced the degree of focal ischemic injury [ 22 ]. Here we demonstrated that puerarin-pretreatment improves behaviors in I/R rats, as observed the MWM test, thereby suggesting that puerarin benefits the recovery of hippocampus-related behaviors.…”

Effects of Puerarin on the Prevention and Treatment of Cardiovascular Diseases

“…It was resulted in an enhancement of protective activity against cerebral ischemic damage in a mouse model of ischemia/reperfusion-evoked dementia. Specifically, these two derivatives showed stronger suppression of inflammation (iNOS activity) and elevation of brain cortex Ca 2+ -Mg 2+ -ATPase activity ( Ji et al, 2016b ). Puerarin-7- O -glucuronide ( Figure 4J ), a water-soluble metabolite of puerarin, lessened intracellular superoxide level and improved total SOD activity, glutathione/glutathione disulfide ratio and total anti-oxidant capacity in xanthine oxidase/xanthine-induced neonatal rat cardiomyocytes.…”