The neuroprotective effect of bisperoxovandium (pyridin-2-squaramide) in intracerebral hemorrhage
| Autor: | Ya Zhang, Jing Cheng, Xin Han, Zhi-Feng Zhang, Hua-Bao Liao, Yang Zhuang, Hai-Bing Zhou, Yang Lei, Juan Chen, Dan Zhao, Xin-Yu Liao, Ying-Ying Zou, Qi Wan, Song-Feng Chen |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
endocrine system viruses Pharmaceutical Science Pharmacology Neuroprotection 03 medical and health sciences 0302 clinical medicine immune system diseases In vivo Drug Discovery Medicine PTEN Viability assay Protein kinase B biology business.industry virus diseases biochemical phenomena metabolism and nutrition In vitro Blot 030104 developmental biology 030220 oncology & carcinogenesis biology.protein Phosphorylation business |
| Zdroj: | Drug Design, Development and Therapy. 13:1957-1967 |
| ISSN: | 1177-8881 |
| DOI: | 10.2147/dddt.s204956 |
| Popis: | Background: The authors have recently designed a new compound bisperoxovandium (pyridin-2-squaramide) [bpV(pis)] and verified that bpV(pis) confers neuroprotection through suppressing PTEN and activating ERK1/2, respectively. Intracerebral hemorrhage (ICH) is the second most common cause of stroke and has severe clinical outcome. In this study, we investigate the effect of bpV(pis) in ICH model both in vivo and in vitro. Materials and methods: The novel drug bpV(pis) was synthesized in the Faculty of Pharmacy, Wuhan University School of Medicine. An ICH model was generated on both SD rats and cells. bpV(pis) was injected into intracerebroventricular or culture media. Western blotting was applied to test the signal pathway. To determine the effect of bpV(pis) on PTEN inhibition and ERK1/2 activation, we measured the phosphorylation level of AKT (a direct downstream target of PTEN that negatively regulates AKT) and ERK1/2. FJC, MTT, and LDH were applied to measure the cell viability. Neurobehavioral tests were performed to measure the effect of bpV(pis). Results: The in vivo results showed that intracerebroventricular administration of bpV(pis) significantly alleviates hematoma, the damage of brain-blood barrier and brain edema. The in vitro results demonstrated that bpV(pis) treatment reduces ICH-induced neuronal injury. Western blotting results identified that bpV(pis) exerts a neuroprotective effect by significantly increasing the phosphorylation level of AKT and ERK1/2 after experimental ICH. Neurobehavioral tests indicate that bpV(pis) promotes functional recovery in ICH animals. Conclusion: This study provides first and direct evidence for a potential role of bpV(pis) in ICH therapy. |
| Databáze: | OpenAIRE |
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