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.
Keywords: Cerebral ischaemia; molecular mechanism; network pharmacology; neuronal apoptosis; traditional Chinese medicine.