Key Laboratory of Molecular Target & Clinical Pharmacology and the State & NMPA Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences & The Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou 511436, China.
The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Guangzhou Medical University, Guangzhou, Qingyuan 511500, China.
Biomed Res Int. 2022 Mar 2;2022:4293265. doi: 10.1155/2022/4293265. eCollection 2022.
Through a network pharmacology method, we screened the main active compounds of Citri Reticulatae Pericarpium (CRP), constructed a drug-ingredient-disease-target network, explored the molecular mechanism of its treatment of myocardial hypertrophy, and validated it by using molecular biology approach.
Traditional Chinese Medicine Systems Pharmacology (TCMSP) and GeneCards were utilised to collect the effective component in CRP and the targets of CRP and myocardial hypertrophy. The STRING database constructed the protein interaction network. The drug-ingredient-disease-target network was outlined by the Cytoscape 3.9.0 software. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted using the Metascape database. Real-time PCR (RT-PCR) and Western blotting were utilised to determine the mRNA and protein level of the critical targets of CRP therapy for myocardial hypertrophy.
We found that five practical components of CRP exerted therapeutic effects on myocardial hypertrophy by modulating 41 targets. Further analysis revealed that naringenin was the essential active compound in CRP that regulated myocardial hypertrophy. In addition, we showed that the active compounds of CRP might exert antihypertrophy effects via regulating essential target proteins such as AKT1-, MAPK3-, PPARA-, PPARG-, and ESR1-mediated signaling pathways such as cell proliferation, nuclear receptor activation, and oxidative stress. The molecular biology experiments demonstrated that naringenin inhibited the mRNA level of NPPA and NPPB induced by Ang II and regulated related targets such as AKT1, MAPK3, PPARA, PPARG, and ESR1.
CRP could inhibit myocardial hypertrophy through multitarget and multiapproach.
通过网络药理学方法，筛选陈皮的主要活性化合物，构建药物-成分-疾病-靶标网络，探讨其治疗心肌肥厚的分子机制，并通过分子生物学方法进行验证。
利用中药系统药理学（TCMSP）和 GeneCards 收集陈皮的有效成分和陈皮及心肌肥厚的靶点。STRING 数据库构建蛋白质相互作用网络。Cytoscape 3.9.0 软件构建药物-成分-疾病-靶标网络。使用 Metascape 数据库进行基因本体（GO）和京都基因与基因组百科全书（KEGG）通路富集分析。实时 PCR（RT-PCR）和 Western blot 用于确定 CRP 治疗心肌肥厚的关键靶标 mRNA 和蛋白水平。
我们发现，陈皮的五种有效成分通过调节 41 个靶点对心肌肥厚发挥治疗作用。进一步分析表明，柚皮苷是调节心肌肥厚的陈皮关键活性化合物。此外，我们表明，陈皮的活性化合物可能通过调节 AKT1、MAPK3、PPARA、PPARG 和 ESR1 介导的信号通路，如细胞增殖、核受体激活和氧化应激，发挥抗肥厚作用。分子生物学实验表明，柚皮苷抑制 Ang II 诱导的 NPPA 和 NPPB mRNA 水平，并调节 AKT1、MAPK3、PPARA、PPARG 和 ESR1 等相关靶标。
陈皮可通过多靶点、多途径抑制心肌肥厚。
