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The therapeutic role of Jingchuan tablet on ischaemic cerebral stroke via the HIF-1α/EPO/VEGFA signalling pathway.


ABSTRACT:

Context

Jingchuan tablet (JCT) is a Chinese medicine prescription for treating ischaemic cerebral stroke (ICS). However, its relevant mechanisms remain unclear.

Objective

To unravel the intrinsic mechanisms of JCT anti-ICS.

Materials and methods

'Hongjingtian', 'chuanxiong', 'yanhusuo', 'bingpian', 'cerebral infarction', 'cerebral ischemia' or 'stroke' were used as keywords, and then components, targets and underlying mechanisms of JCT anti-ICS were analysed in TCMSP, TTD, DrugBank, STRING and Metascape databases up to June 2020. Male Sprague-Dawley rats under permanent middle cerebral artery occlusion (pMCAO) model, randomly assigned as: model, sham, nimodipine (0.012 g/kg/d) and JCT (0.78, 1.56 and 3.12 g/kg/d) groups, received oral gavage administration for a week. Therapeutic effects were evaluated by detecting the proportion of cerebral infarction, neuronal apoptosis and neurological deficits. Bioactive components were detected by HPLC-MS. Molecular biology and computational docking were used to verify the underlying mechanisms.

Results

Eighty-one components, 166 targets and HIF-1α/EPO/VEGFA pathway contributed to the anti-ICS effect of JCT. JCT treatment effectively reduced the proportion of cerebral infarction (33.13%), apoptosis rate (14.80%) and neurobehavioural score (2.00). JCT increased the protein levels of HIF-1α (0.84), EPO (0.64) and VEGFA (0.69), respectively (p < 0.05). Gallic acid, salidroside, chlorogenic acid, ethyl gallate, ferulic acid and tetrahydropalmatine detected by HPLC-MS showed good interaction and binding with HIF-1α/EPO/VEGFA.

Conclusions

Our study demonstrated the mechanisms of JCT anti-ICS associated with the activation of the HIF-1α/EPO/VEGFA pathway, which provided a pharmacological basis for expanding the clinical application and some scientific ideas for further research into the material basis JCT anti-ICS.

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC9590438 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Publications

The therapeutic role of Jingchuan tablet on ischaemic cerebral stroke via the HIF-1α/EPO/VEGFA signalling pathway.

Zhang Yan Y   Liu Qinghuan Q   Zhang Ting T   Wang Hong H   Fu Yu Y   Wang Wentong W   Li Dongdong D  

Pharmaceutical biology 20221201 1


<h4>Context</h4>Jingchuan tablet (JCT) is a Chinese medicine prescription for treating ischaemic cerebral stroke (ICS). However, its relevant mechanisms remain unclear.<h4>Objective</h4>To unravel the intrinsic mechanisms of JCT anti-ICS.<h4>Materials and methods</h4>'Hongjingtian', 'chuanxiong', 'yanhusuo', 'bingpian', 'cerebral infarction', 'cerebral ischemia' or 'stroke' were used as keywords, and then components, targets and underlying mechanisms of JCT anti-ICS were analysed in TCMSP, TTD,  ...[more]

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