PMID- 37783074 OWN - NLM STAT- Publisher LR - 20231002 IS - 1879-0534 (Electronic) IS - 0010-4825 (Linking) VI - 166 DP - 2023 Sep 20 TI - Mechanism of XiJiaQi in the treatment of chronic heart failure: Integrated analysis by pharmacoinformatics, molecular dynamics simulation, and SPR validation. PG - 107479 LID - S0010-4825(23)00944-7 [pii] LID - 10.1016/j.compbiomed.2023.107479 [doi] AB - OBJECTIVE: Chronic heart failure (CHF) is a complicated clinical syndrome with a high mortality rate. XiJiaQi (XJQ) is a traditional Chinese medicine used in the clinical treatment of CHF, but its bioactive components and their modes of action remain unknown. This study was designed to unravel the molecular mechanism of XJQ in the treatment of CHF using multiple computer-assisted and experimental methods. METHODS: Pharmacoinformatics-based methods were used to explore the active components and targets of XJQ in the treatment of CHF. ADMETlab was then utilized to evaluate the pharmacokinetic and toxicological properties of core components. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were to explore the underlying mechanism of XJQ treatment. Molecular docking, surface plasmon resonance (SPR), and molecular dynamics (MD) were employed to evaluate the binding of active components to putative targets. RESULTS: Astragaloside IV, formononetin, kirenol, darutoside, periplocin and periplocymarin were identified as core XJQ-related components, and IL6 and STAT3 were identified as core XJQ targets. ADME/T results indicated that periplocin and periplocymarin may have potential toxicity. GO and KEGG pathway analyses revealed that XJQ mainly intervenes in inflammation, apoptosis, diabetes, and atherosclerosis-related biological pathways. Molecular docking and SPR revealed that formononetin had a high affinity with IL6 and STAT3. Furthermore, MD simulation confirmed that formononetin could firmly bind to the site 2 region of IL6 and the DNA binding domain of STAT3. CONCLUSION: This study provides a mechanistic rationale for the clinical application of XJQ. Modulation of STAT3 and IL-6 by XJQ can impact CHF, further guiding research efforts into the molecular underpinnings of CHF. CI - Copyright (c) 2023 The Authors. Published by Elsevier Ltd.. All rights reserved. FAU - Zhao, Dongyang AU - Zhao D AD - State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China. FAU - Guo, Kaijing AU - Guo K AD - State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China. FAU - Zhang, Qian AU - Zhang Q AD - Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China. FAU - Wu, Yan AU - Wu Y AD - State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China. FAU - Ma, Chen AU - Ma C AD - State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China. FAU - He, Wenyi AU - He W AD - State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China. FAU - Jin, Xiangju AU - Jin X AD - State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China. FAU - Zhang, Xinyu AU - Zhang X AD - State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China. FAU - Wang, Yanan AU - Wang Y AD - State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China. Electronic address: wangyanan@imm.ac.cn. FAU - Lin, Sheng AU - Lin S AD - Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China. Electronic address: lsznn@bucm.edu.cn. FAU - Shang, Hongcai AU - Shang H AD - Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China. Electronic address: shanghongcai@126.com. LA - eng PT - Journal Article DEP - 20230920 PL - United States TA - Comput Biol Med JT - Computers in biology and medicine JID - 1250250 SB - IM OTO - NOTNLM OT - Chronic heart failure OT - Molecular docking OT - Molecular dynamics simulation OT - Pharmacoinformatics OT - Surface plasmon resonance OT - Traditional Chinese medicine OT - XiJiaQi formula COIS- Declaration of competing interest The authors declare no conflict of interest. EDAT- 2023/10/02 18:41 MHDA- 2023/10/02 18:41 CRDT- 2023/10/02 18:05 PHST- 2023/06/20 00:00 [received] PHST- 2023/08/27 00:00 [revised] PHST- 2023/09/15 00:00 [accepted] PHST- 2023/10/02 18:41 [medline] PHST- 2023/10/02 18:41 [pubmed] PHST- 2023/10/02 18:05 [entrez] AID - S0010-4825(23)00944-7 [pii] AID - 10.1016/j.compbiomed.2023.107479 [doi] PST - aheadofprint SO - Comput Biol Med. 2023 Sep 20;166:107479. doi: 10.1016/j.compbiomed.2023.107479.