Integrated transcriptomics and metabolomics analysis reveals that C3 and C5 are vital targets of DuZhi Wan in protecting against cerebral ischemic injury - 18/10/22
, Jing-jing Zhang a, c, ⁎ Abstract |
Background/Aims |
Duzhi Wan (DZW) has been extensively used in the prevention and treatment of ischemic stroke, but the mechanisms underlying its effects remain unclear. In this study, a combination of transcriptomics, metabolomics and network analysis was applied to identify the preventive mechanism of DZW in middle cerebral artery occlusion (MCAO)-induced ischemia/reperfusion (I/R) injury.
Methods |
The mice were divided into five groups: the sham group, I/R group, I/R + Ginaton group, I/R+DZW-L group, and I/R+DZW-H group. Neurological deficit scores and regional cerebral blood flow (rCBF), hematoxylin and eosin (H&E) and Nissl staining results were evaluated. Transcriptomics analysis and metabolomics analysis were applied to identify the key genes and metabolites, and qRT-PCR, ELISA, and immunofluorescence were applied to verify the key targets.
Results |
DZW significantly decreased the infarction size and neurological deficit scores, increased the rCBF percentage and neuronal number and improved neuronal morphology after MCAO. Transcriptomics and metabolomics analysis revealed that C3 and C5ar1 were core targets of DZW and indirectly regulated downstream purine metabolism, the pentose phosphate pathway, and glycerophospholipid metabolism-associated pathways via inflammatory cells. Moreover, ELISA, qRT-PCR, and immunofluorescence further confirmed that DZW significantly decreased the expression of C3, C5ar1, C5 and downstream inflammatory cytokines, including IL-6, IL-1β and MMP-9, at the gene and protein levels, suggesting that DZW decreased neuroinflammation and inhibited related metabolic pathways.
Conclusion |
C3 and C5 play important roles in the neuroprotective and antineuroinflammatory effects of DZW in protecting against cerebral I/R. This study provides novel insights into the neuroprotective effects of DZW and its clinical application.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
Highlights |
• | Protective effects of Duzhi Wan (DZW) on ischemic stroke were investigated. |
• | DZW effectively inhibited neuroinflammatory response. |
• | Transcriptomic and metabolomic analysis revealed that C3 and C5ar1 were core targets and acetylchonline, cyclic GMP, D-erythrose-4-phosphate, xanthine, gluconolactone, inosine 5’-monophosphate, and xanthylic acid were key genes and metabolites in the neuroprotective effect of DZW. |
• | C3 and C5 are Vital Targets of DZW in Protecting Against Cerebral Ischemic Injury via integrated Transcriptomics and Metabolomics Analysis. |
Abbreviations : ANOVA, BP, CC, C3, C5, C5ar1, DEG, DM, DZW, ELISA, G6PD, GO, H&E, ICA, IL-1β, IL-6, I/R, KEGG, MCAO, MF, MMP-9, OPLS-DA, PPI, rCBF, rtPA, TCM
Keywords : Cerebral ischemia/reperfusion injury, Duzhi Wan (DZW), C3, C5, Neuroprotection, Antineuroinflammation
Plan
Vol 155
Article 113703- novembre 2022 Retour au numéro
Article précédent
- Influence of esomeprazole on the bioavailability of afatinib: A pharmacokinetic cross-over study in patients with non-small cell lung cancer
- G.D. Marijn Veerman, Daan P. Hurkmans, Marthe S. Paats, Esther Oomen-de Hoop, Cor H. van der Leest, Eric R.E. van Thiel, Joachim G.J.V. Aerts, Roelof W. van Leeuwen, Anne-Marie C. Dingemans, Ron H.J. Mathijssen
- Acute myocardial infarction therapy using calycosin and tanshinone co-loaded mitochondria targeted lipid-polymer hybrid nano-system: Preparation, characterization, and anti myocardial infarction activity assessment
- Jieke Yan, Jing Guo, Yuzhen Wang, Xiaowei Xing, Xuguang Zhang, Guanghao Zhang, Zhaoqiang Dong
Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
Déjà abonné à cette revue ?