Rheum palmatum L. and Salvia miltiorrhiza Bge. Alleviates Acute Pancreatitis by Regulating Th17 Cell Differentiation: An Integrated Network Pharmacology Analysis, Molecular Dynamics Simulation and Experimental Validation

作     者：FENG Min-chao LUO Fang HUANG Liang-jiang LI Kai CHEN Zu-min LI Hui YAO Chun QIN Bai-jun CHEN Guo-zhong 

作者机构：The First Clinical Medical CollegeGuangxi University of Traditional Chinese MedicineNanning 530000China Guangxi Key Laboratory of Molecular Biology of Traditional Chinese Medicine and Preventive MedicineNanning 530000China Graduate SchoolGuangxi University of Traditional Chinese MedicineNanning 530000China Department of Gastroenterologythe First Affiliated Hospital of Guangxi University of Traditional Chinese MedicineNanning 530023China 

出 版 物：《Chinese Journal of Integrative Medicine》 (中国结合医学杂志（英文版）)

年 卷 期：2024年第30卷第5期

页      面：408-420页

核心收录：

学科分类：1006[医学-中西医结合] 1002[医学-临床医学] 10[医学] 100602[医学-中西医结合临床] 

基　　金：Supported by National Natural Science Foundation of China (No.82160890, 82260899) Innovation Project of Guangxi Graduate Education (No.YCSW2023383)。 

主　　题：Rheum palmatum L. Salvia miltiorrhiza Bge. molecular docking simulation network pharmacology acute pancreatitis Th17 cell differentiation 

摘      要：Objective: To identify the core targets of Rheum palmatum L. and Salvia miltiorrhiza Bge.,(Dahuang-Danshen, DH-DS) and the mechanism underlying its therapeutic efficacy in acute pancreatitis(AP)using a network pharmacology approach and validate the findings in animal experiments. Methods: Network pharmacology analysis was used to elucidate the mechanisms underlying the therapeutic effects of DH-DS in AP. The reliability of the results was verified by molecular docking simulation and molecular dynamics simulation.Finally, the results of network pharmacology enrichment analysis were verified by immunohistochemistry,Western blot analysis and real-time quantitative PCR, respectively. Results: Sixty-seven common targets of DH-DS in AP were identified and mitogen-activated protein kinase 3(MAPK3), Janus kinase 2(JAK2), signal transducer and activator of transcription 3(STAT3), protein c-Fos(FOS) were identified as core targets in the protein interaction(PPI) network analysis. Gene ontology analysis showed that cellular response to organic substance was the main functions of DH-DS in AP, and Kyoto Encyclopedia of Genes and Genomes analysis showed that the main pathway included Th17 cell differentiation. Molecular docking simulation confirmed that DH-DS binds with strong affinity to MAPK3, STAT3 and FOS. Molecular dynamics simulation revealed that FOS-isotanshinone Ⅱ and STAT3-dan-shexinkum d had good binding capacity. Animal experiments indicated that compared with the AP model group, DH-DS treatment effectively alleviated AP by inhibiting the expression of interleukin-1β, interleukin-6 and tumor necrosis factor-α, and blocking the activation of Th17 cell differentiation(P0.01). Conclusion: DH-DS could inhibit the expression of inflammatory factors and protect pancreatic tissues,which would be functioned by regulating Th17 cell differentiation-related m RNA and protein expressions.