PMID- 34258872 OWN - NLM STAT- MEDLINE DCOM- 20220202 LR - 20220202 IS - 1582-4934 (Electronic) IS - 1582-1838 (Print) IS - 1582-1838 (Linking) VI - 25 IP - 15 DP - 2021 Aug TI - Effect of dapagliflozin on diabetic patients with cardiovascular disease via MAPK signalling pathway. PG - 7500-7512 LID - 10.1111/jcmm.16786 [doi] AB - Clinical studies have shown that dapagliflozin can reduce cardiovascular outcome in patients with type 2 diabetes mellitus (T2DM), but the exact mechanism is unclear. In this study, we used the molecular docking and network pharmacology methods to explore the potential mechanism of dapagliflozin on T2DM complicated with cardiovascular diseases (CVD). Dapagliflozin's potential targets were predicted via the Swiss Target Prediction platform. The pathogenic targets of T2DM and CVD were screened by the Online Mendelian Inheritance in Man (OMIM) and Gene Cards databases. The common targets of dapagliflozin, T2DM and CVD were used to establish a protein-protein interaction (PPI) network; the potential protein functional modules in the PPI network were found out by MCODE. Metascape tool was used for Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analysis. A potential protein functional module with the best score was obtained from the PPI network and 9 targets in the protein functional module all showed good binding properties when docking with dapagliflozin. The results of KEGG pathway enrichment analysis showed that the underlying mechanism mainly involved AGE-RAGE signalling pathway in diabetic complications, TNF signalling pathway and MAPK signalling pathway. Significantly, the MAPK signalling pathway was considered as the key pathway. In conclusion, we speculated that dapagliflozin played a therapeutic role in T2DM complicated with CVD mainly through MAPK signalling pathway. This study preliminarily reveals the possible mechanism of dapagliflozin in the treatment of T2DM complicated with CVD and provides a theoretical basis for future clinical research. CI - (c) 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. FAU - Yue, Zhaodi AU - Yue Z AUID- ORCID: 0000-0003-2864-2729 AD - Department of rehabilitation medicine, Department of Endocrinology and Metabology, The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, China. AD - Department of Endocrinology and Metabology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational medicine, Shandong Institute of Nephrology, Jinan, China. AD - College of Rehabilitation Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China. FAU - Li, Li AU - Li L AD - Department of rehabilitation medicine, Department of Endocrinology and Metabology, The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, China. FAU - Fu, Hui AU - Fu H AD - The Clinical Medical College, Cheeloo Medical College of Shandong University, Jinan, China. FAU - Yin, Yanyan AU - Yin Y AD - Department of rehabilitation medicine, Department of Endocrinology and Metabology, The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, China. AD - Department of Endocrinology and Metabology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational medicine, Shandong Institute of Nephrology, Jinan, China. AD - College of Rehabilitation Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China. FAU - Du, Bingyu AU - Du B AD - Department of rehabilitation medicine, Department of Endocrinology and Metabology, The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, China. AD - Department of Endocrinology and Metabology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational medicine, Shandong Institute of Nephrology, Jinan, China. AD - College of Rehabilitation Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China. FAU - Wang, Fangqi AU - Wang F AD - College of Rehabilitation Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China. FAU - Ding, Yi AU - Ding Y AD - Department of rehabilitation medicine, Department of Endocrinology and Metabology, The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, China. FAU - Liu, Yibo AU - Liu Y AD - Department of rehabilitation medicine, Department of Endocrinology and Metabology, The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, China. AD - Department of Endocrinology and Metabology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational medicine, Shandong Institute of Nephrology, Jinan, China. AD - College of Rehabilitation Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China. FAU - Zhao, Renjie AU - Zhao R AD - Department of rehabilitation medicine, Department of Endocrinology and Metabology, The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, China. AD - Department of Endocrinology and Metabology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational medicine, Shandong Institute of Nephrology, Jinan, China. AD - College of Rehabilitation Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China. FAU - Zhang, Zhongwen AU - Zhang Z AD - Department of Endocrinology and Metabology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational medicine, Shandong Institute of Nephrology, Jinan, China. FAU - Yu, Shaohong AU - Yu S AD - Department of rehabilitation medicine, Department of Endocrinology and Metabology, The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, China. AD - The Second Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210714 PL - England TA - J Cell Mol Med JT - Journal of cellular and molecular medicine JID - 101083777 RN - 0 (Benzhydryl Compounds) RN - 0 (Glucosides) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 1ULL0QJ8UC (dapagliflozin) SB - IM MH - Benzhydryl Compounds/*pharmacology/therapeutic use MH - Diabetic Cardiomyopathies/*drug therapy/metabolism MH - Glucosides/*pharmacology/therapeutic use MH - Humans MH - MAP Kinase Signaling System/*drug effects MH - Molecular Docking Simulation MH - *Network Pharmacology MH - Protein Interaction Mapping MH - Sodium-Glucose Transporter 2 Inhibitors/*pharmacology/therapeutic use PMC - PMC8335696 OTO - NOTNLM OT - cardiovascular disease OT - dapagliflozin OT - network pharmacology OT - type 2 diabetes mellitus COIS- The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2021/07/15 06:00 MHDA- 2022/02/03 06:00 PMCR- 2021/08/01 CRDT- 2021/07/14 07:27 PHST- 2021/06/22 00:00 [revised] PHST- 2021/05/04 00:00 [received] PHST- 2021/06/28 00:00 [accepted] PHST- 2021/07/15 06:00 [pubmed] PHST- 2022/02/03 06:00 [medline] PHST- 2021/07/14 07:27 [entrez] PHST- 2021/08/01 00:00 [pmc-release] AID - JCMM16786 [pii] AID - 10.1111/jcmm.16786 [doi] PST - ppublish SO - J Cell Mol Med. 2021 Aug;25(15):7500-7512. doi: 10.1111/jcmm.16786. Epub 2021 Jul 14.