Article ; Online: Neuroprotective effects of Jie-du-huo-xue decoction on microglia pyroptosis after cerebral ischemia and reperfusion--From the perspective of glial-vascular unit.
2023 Volume 318, Issue Pt B, Page(s) 116990
Abstract: ... of life. Jie-Du-Huo-Xue decoction (JDHXD) is a classical and well-known Chinese formula for stroke ...
Abstract | Ethnopharmacological relevance: Ischemic stroke poses a serious risk to public health and quality of life. Jie-Du-Huo-Xue decoction (JDHXD) is a classical and well-known Chinese formula for stroke treatment, but the pharmacological mechanism is still unclear. Aim of the study: This study aims to investigate the mechanism underlying microglial pyroptosis and polarization, as well as the potential efficacy of JDHXD against cerebral ischemia-reperfusion injury (CIRI). Materials and methods: Models of CIRI were established by the middle cerebral artery occlusion/reperfusion (MCAO/R) method in rats. In the first stage, 36 SD rats were randomly divided into sham group, I/R group, JDHXD-L group (5.36 g/kg/day), JDHXD-M group (10.71 g/kg/day), JDHXD-H group (21.42 g/kg/day), and positive drug edaravone group. The effectiveness of JDHXD on CIRI was confirmed by neurological function testing and cerebral infarct measuring. The best dose (JDXHD-M) was subsequently chosen to perform the tests that followed. In the second stage, 36 SD rats were randomly divided into the sham group, the I/R group, and the JDHXD-M group. Detection of nerve damage using Nissl staining, proteins of pyroptosis, Iba-1, and NeuN expressions were detected by western blotting, and proteins of microglial pyroptosis and M1/M2 phenotypic polarization were detected by immunofluorescence. Results: In rats after CIRI, JDHXD significantly reduced neurological impairment and cerebral infarction. In addition, JDHXD facilitated the M1-to-M2 transition of microglia in order to minimize neuroinflammation and improve anti-inflammatory repair. In addition, JDXHD inhibited microglial pyroptosis by blocking the cleavage of caspase-1 P10 and gasdermin D, hence reducing neuronal damage and enhancing neuronal survival following reperfusion. Interestingly, JDHXD also demonstrated a protective effect on the glial-vascular unit (GVU). Conclusions: Our investigation demonstrated that JDHXD exerted a GVU-protective effect on CIRI rats by decreasing neuroinflammation-associated microglial pyroptosis, suppressing microglial M1 activation, and promoting microglial M2 activation. |
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MeSH term(s) | Rats ; Animals ; Microglia ; Pyroptosis ; Neuroprotective Agents/pharmacology ; Neuroprotective Agents/therapeutic use ; Neuroprotective Agents/metabolism ; Neuroinflammatory Diseases ; Quality of Life ; Rats, Sprague-Dawley ; Brain Ischemia/drug therapy ; Brain Ischemia/metabolism ; Infarction, Middle Cerebral Artery/drug therapy ; Infarction, Middle Cerebral Artery/metabolism ; Reperfusion Injury/drug therapy ; Reperfusion Injury/metabolism ; Reperfusion |
Chemical Substances | Neuroprotective Agents |
Language | English |
Publishing date | 2023-08-01 |
Publishing country | Ireland |
Document type | Journal Article |
ZDB-ID | 134511-4 |
ISSN | 1872-7573 ; 0378-8741 |
ISSN (online) | 1872-7573 |
ISSN | 0378-8741 |
DOI | 10.1016/j.jep.2023.116990 |
Database | MEDical Literature Analysis and Retrieval System OnLINE |
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