The First Affiliated Hospital, Hunan University of Chinese Medicine, 95 Shaoshan Road, Changsha, Hunan, 410007, China; Hunan University of Chinese Medicine, 300 Xueshi Road, Changsha, Hunan, 410006, China.
The First Affiliated Hospital, Hunan University of Chinese Medicine, 95 Shaoshan Road, Changsha, Hunan, 410007, China; Hunan Academy of Chinese Medicine, 58 Lushan Road, Changsha, Hunan, 410007, China; Hunan University of Chinese Medicine, 300 Xueshi Road, Changsha, Hunan, 410006, China.
J Ethnopharmacol. 2024 Jan 30;319(Pt 3):117218. doi: 10.1016/j.jep.2023.117218. Epub 2023 Oct 6.
Promoting the recovery of cerebral blood circulation after cerebral infarction (CI) is an important intervention. Buyang Huanwu decoction (BHD) is a classic prescription for treating CI that promotes angiogenesis. Cytoplasmic glycolysis ischaemic-region cells after CI may be highly activated to maintain metabolic activity under hypoxia. From the perspective of long-term maintenance of glycolytic metabolism in the ischaemic area after CI, it may be beneficial to promote angiogenesis and maintain glial cell activation and neuronal survival. In this context, the regulatory relationship of lncRNAs and miRNAs with mRNAs is worthy of attention. Mining the competitive binding relationships among RNAs will aid in the screening of key gene targets post-CI. In this study, network pharmacology and bioinformatics were used to construct a ceRNA network, screen key targets, and explore the effect of glycolysis on angiogenesis during BHD-mediated CI regulation.
This study aimed to explore the effect of BHD on angiogenesis after glycolysis regulation in CI.
According to the 21 active BHD ingredients we identified by our research team, we conducted network pharmacology. BHD targets that can regulate glycolysis and angiogenesis after CI were screened from the GeneCards, CTD and OMIM databases. We retrieved CI-related datasets from the GEO database and screened for differentially expressed lncRNAs and miRNAs. LncRNA‒miRNA-mRNA/TF targeting relationships were screened and organized with the miRcode, miRDB, TargetScan, miRWalk, and TransmiR v2.0 databases. Cytoscape was used to construct an lncRNA‒miRNA-mRNA/TF ceRNA network. Through BioGPS, key mRNAs/TFs in the network were screened for enrichment analysis. Animal experiments were then conducted to validate some key mRNAs/TFs and enriched signalling pathways.
PFKFB3 and other genes may help regulate glycolysis and angiogenesis through AMPK and other signalling pathways. The anti-CI effect of BHD may involve maintaining activation of genes such as AMPK and PFKFB3 in the ischaemic cortex, maintaining moderate glycolysis levels in brain tissue, and promoting angiogenesis.
BHD can regulate glycolysis and promote angiogenesis after CI through multiple pathways and targets, in which AMPK signalling pathway activation may be important.
促进脑梗死（CI）后脑血液循环的恢复是一种重要的干预措施。补阳还五汤（BHD）是治疗 CI 的经典方剂，可促进血管生成。CI 后缺血区细胞的细胞质糖酵解可能高度活跃，以在缺氧下维持代谢活性。从 CI 后缺血区糖酵解代谢的长期维持的角度来看，促进血管生成并维持神经胶质细胞的激活和神经元的存活可能是有益的。在这种情况下，lncRNA 和 miRNA 与 mRNAs 的调节关系值得关注。挖掘 RNA 之间的竞争结合关系将有助于筛选 CI 后关键基因靶标。在这项研究中，我们使用网络药理学和生物信息学构建了一个 ceRNA 网络，筛选关键靶点，并探讨了 BHD 介导的 CI 调节中糖酵解对血管生成的影响。
本研究旨在探讨 BHD 在 CI 后糖酵解调节对血管生成的影响。
根据我们研究团队确定的 21 种活性 BHD 成分，我们进行了网络药理学研究。从 GeneCards、CTD 和 OMIM 数据库中筛选出可调节 CI 后糖酵解和血管生成的 BHD 靶点。我们从 GEO 数据库中检索与 CI 相关的数据集，并筛选差异表达的 lncRNA 和 miRNA。使用 miRcode、miRDB、TargetScan、miRWalk 和 TransmiR v2.0 数据库筛选并组织 lncRNA-miRNA-mRNA/TF 靶向关系。使用 Cytoscape 构建 lncRNA-miRNA-mRNA/TF ceRNA 网络。通过 BioGPS，筛选网络中的关键 mRNAs/TFs 进行富集分析。然后进行动物实验验证一些关键的 mRNAs/TFs 和富集的信号通路。
PFKFB3 和其他基因可能通过 AMPK 等信号通路帮助调节糖酵解和血管生成。BHD 的抗 CI 作用可能涉及维持缺血皮质中 AMPK 和 PFKFB3 等基因的激活，维持脑组织中适度的糖酵解水平，并促进血管生成。
BHD 可通过多种途径和靶点调节 CI 后糖酵解和促进血管生成，其中 AMPK 信号通路的激活可能很重要。
