Department of General Surgery (Gastrointestinal Surgery), The Affiliated Hospital of Southwest Medical University, 25 Taiping Street, Jiangyang District, Luzhou, Sichuan, China.
Department of Emergency Medicine, The Affiliated Hospital of Southwest Medical University, 25 Taiping Street, Jiangyang District, Luzhou, Sichuan, China.
BMC Infect Dis. 2024 Jul 12;24(1):695. doi: 10.1186/s12879-024-09589-2.
Sepsis is a life-threatening organ dysfunction, which seriously threatens human health. The clinical and experimental results have confirmed that Traditional Chinese medicine (TCM), such as Scutellariae Radix, has anti-inflammatory effects. This provides a new idea for the treatment of sepsis. This study systematically analyzed the mechanism of Scutellariae Radix treatment in sepsis based on network pharmacology, RNA sequencing and molecular docking.
Gene expression analysis was performed using Bulk RNA sequencing on sepsis patients and healthy volunteers. After quality control of the results, the differentially expressed genes (DEGs) were analyzed. The active ingredients and targets of Scutellariae Radix were identified using The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Gene Ontology (GO) and Protein-Protein Interaction (PPI) analysis were performed for disease-drug intersection targets. With the help of GEO database, Survival analysis and Meta-analysis was performed on the cross-targets to evaluate the prognostic value and screen the core targets. Subsequently, single-cell RNA sequencing was used to determine where the core targets are located within the cell. Finally, in this study, molecular docking experiments were performed to further clarify the interrelationship between the active components of Scutellariae Radix and the corresponding targets.
There were 72 active ingredients of Scutellariae Radix, and 50 common targets of drug and disease. GO and PPI analysis showed that the intersection targets were mainly involved in response to chemical stress, response to oxygen levels, response to drug, regulation of immune system process. Survival analysis showed that PRKCD, EGLN1 and CFLAR were positively correlated with sepsis prognosis. Meta-analysis found that the three genes were highly expressed in sepsis survivor, while lowly in non-survivor. PRKCD was mostly found in Macrophages, while EGLN1 and CFLAR were widely expressed in immune cells. The active ingredient Apigenin regulates CFLAR expression, Baicalein regulates EGLN1 expression, and Wogonin regulates PRKCD expression. Molecular docking studies confrmed that the three active components of astragalus have good binding activities with their corresponding targets.
Apigenin, Baicalein and Wogonin, important active components of Scutellaria Radix, produce anti-sepsis effects by regulating the expression of their targets CFLAR, EGLN1 and PRKCD.
脓毒症是一种危及生命的器官功能障碍，严重威胁着人类的健康。临床和实验结果证实，黄芩等中药具有抗炎作用。这为脓毒症的治疗提供了新的思路。本研究基于网络药理学、RNA 测序和分子对接，系统分析了黄芩治疗脓毒症的作用机制。
采用 Bulk RNA 测序对脓毒症患者和健康志愿者进行基因表达分析。对结果进行质量控制后，分析差异表达基因（DEGs）。利用中药系统药理学数据库和分析平台（TCMSP）鉴定黄芩的活性成分和靶点。对疾病-药物靶点进行基因本体（GO）和蛋白质-蛋白质相互作用（PPI）分析。借助 GEO 数据库，对交叉靶点进行生存分析和 Meta 分析，评价其预后价值并筛选核心靶点。随后，采用单细胞 RNA 测序确定核心靶点在细胞内的位置。最后，在本研究中，进行了分子对接实验，以进一步阐明黄芩活性成分与相应靶点之间的相互关系。
黄芩有 72 种活性成分，药物与疾病有 50 个共同靶点。GO 和 PPI 分析表明，交集靶点主要参与对化学应激、氧水平、药物反应、免疫系统过程的调节。生存分析表明，PRKCD、EGLN1 和 CFLAR 与脓毒症的预后呈正相关。Meta 分析发现，这三个基因在脓毒症幸存者中高表达，而非幸存者中低表达。PRKCD 主要在巨噬细胞中发现，而 EGLN1 和 CFLAR 在免疫细胞中广泛表达。活性成分芹菜素调节 CFLAR 的表达，黄芩素调节 EGLN1 的表达，和白杨素调节 PRKCD 的表达。分子对接研究证实，黄芩的三种重要活性成分与相应的靶标具有良好的结合活性。
黄芩的重要活性成分芹菜素、黄芩素和白杨素通过调节其靶标 CFLAR、EGLN1 和 PRKCD 的表达，发挥抗脓毒症作用。
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