TY - JOUR
T1 - Effects and Potential Mechanism of Zhuyu Pill Against Atherosclerosis
T2 - Network Pharmacology and Experimental Validation
AU - Pan, Yingying
AU - Feng, Xianrong
AU - Song, Wei
AU - Zhou, Xin
AU - Zhou, Zhen
AU - Chen, Gaoyang
AU - Shen, Tao
AU - Zhang, Xiaobo
N1 - Funding Information:
The financial support of the study was provided by the National Natural Science Foundation of China (No: 81973743), Key Research and Development Program of Sichuan Provincial Department of Science and Technology (No: 22ZDYF0905), Sichuan Science and Technology Innovation Seedling Project (No: 20MZGC0241), and “Xinglin Scholar” discipline talents Research Enhancement Programme of Chengdu University of Traditional Chinese Medicine (No: BSH2021016).
Publisher Copyright:
© 2023 Pan et al. This work is published and licensed by Dove Medical Press Limited.
PY - 2023
Y1 - 2023
N2 - Background: Atherosclerosis (AS) is an immunoinflammatory disease associated with dyslipidemia. Zhuyu Pill (ZYP) is a classic Chinese herbal compound that has been shown to exhibit anti-inflammatory and lipid-lowering effects on AS in our previous studies. However, the underlying mechanisms by which ZYP ameliorates atherosclerosis have not yet been fully investigated. In this study, network pharmacology and in vivo experiments were conducted to explore the underlying pharmacological mechanisms of ZYP on ameliorating AS. Methods: The active ingredients of ZYP were acquired from our previous study. The putative targets of ZYP relevant to AS were obtained from TCMSP, SwissTargetPrediction, STITCH, DisGeNET, and GeneCards databases. Protein-protein interactions (PPI) network, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were conducted using the Cytoscape software. Furthermore, in vivo experiments were carried out for target validation in apolipoprotein E (ApoE)-/-mice. Results: Animal experiments revealed that ZYP ameliorated AS mainly through lowering blood lipids, alleviating vascular inflammation, and decreasing the levels of vascular cell adhesion molecule-1 (VCAM1), intercellular adhesion molecule-1 (ICAM1), monocyte chemotactic protein-1 (MCP-1), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α). Additionally, the results of RealTime quantitative PCR revealed that ZYP inhibited the gene expressions of mitogen-activated protein kinase (MAPK) p38, extracellular regulated protein kinases (ERK), c-Jun N-terminal kinase (JNK), and nuclear factor kappa-B (NF-κB) p65. The Immunohistochemistry and Western blot assays showed the inhibitory effect of ZYP on the proteins level of p38, p-p38, p65, and p-p65. Conclusion: This study has provided valuable evidence on the pharmacological mechanisms of action of ZYP in ameliorating AS that will be useful for forming the rationale of future research studying the cardio-protection and anti-inflammation effects of ZYP.
AB - Background: Atherosclerosis (AS) is an immunoinflammatory disease associated with dyslipidemia. Zhuyu Pill (ZYP) is a classic Chinese herbal compound that has been shown to exhibit anti-inflammatory and lipid-lowering effects on AS in our previous studies. However, the underlying mechanisms by which ZYP ameliorates atherosclerosis have not yet been fully investigated. In this study, network pharmacology and in vivo experiments were conducted to explore the underlying pharmacological mechanisms of ZYP on ameliorating AS. Methods: The active ingredients of ZYP were acquired from our previous study. The putative targets of ZYP relevant to AS were obtained from TCMSP, SwissTargetPrediction, STITCH, DisGeNET, and GeneCards databases. Protein-protein interactions (PPI) network, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were conducted using the Cytoscape software. Furthermore, in vivo experiments were carried out for target validation in apolipoprotein E (ApoE)-/-mice. Results: Animal experiments revealed that ZYP ameliorated AS mainly through lowering blood lipids, alleviating vascular inflammation, and decreasing the levels of vascular cell adhesion molecule-1 (VCAM1), intercellular adhesion molecule-1 (ICAM1), monocyte chemotactic protein-1 (MCP-1), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α). Additionally, the results of RealTime quantitative PCR revealed that ZYP inhibited the gene expressions of mitogen-activated protein kinase (MAPK) p38, extracellular regulated protein kinases (ERK), c-Jun N-terminal kinase (JNK), and nuclear factor kappa-B (NF-κB) p65. The Immunohistochemistry and Western blot assays showed the inhibitory effect of ZYP on the proteins level of p38, p-p38, p65, and p-p65. Conclusion: This study has provided valuable evidence on the pharmacological mechanisms of action of ZYP in ameliorating AS that will be useful for forming the rationale of future research studying the cardio-protection and anti-inflammation effects of ZYP.
KW - atherosclerosis
KW - MAPK
KW - network pharmacology
KW - NF-κB
KW - Zhuyu Pill
UR - http://www.scopus.com/inward/record.url?scp=85149103691&partnerID=8YFLogxK
U2 - 10.2147/DDDT.S398808
DO - 10.2147/DDDT.S398808
M3 - Article
C2 - 36866196
AN - SCOPUS:85149103691
SN - 1177-8881
VL - 17
SP - 597
EP - 612
JO - Drug Design, Development and Therapy
JF - Drug Design, Development and Therapy
ER -