PMID- 35178959
OWN - NLM
STAT- MEDLINE
DCOM- 20220221
LR  - 20220221
IS  - 1001-5302 (Print)
IS  - 1001-5302 (Linking)
VI  - 47
IP  - 3
DP  - 2022 Feb
TI  - [Mechanism of Carthami Flos and Lepidii Semen drug pair in inhibition of 
      myocardial fibrosis by improving cardiac microenvironment based on network 
      pharmacology and animal experiment].
PG  - 753-763
LID - 10.19540/j.cnki.cjcmm.20210929.401 [doi]
AB  - Previously, Carthami Flos and Lepidii Semen(CF-LS) drug pair has been proved 
      effective in inhibiting myocardial fibrosis(MF) by blunting the activity of 
      cardiac fibroblasts. The present study explored the underlying mechanism of CF-LS 
      in inhibiting MF by improving the cardiac microenvironment based on network 
      pharmacology combined with experimental verification. Active compounds and 
      potential targets of CF-LS were retrieved from Traditional Chinese Medicine 
      Systems Pharmacology Database and Analysis Platform(TCMSP), and the potential 
      targets of MF were obtained from GeneCards, Online Mendelian Inheritance in 
      Man(OMIM), and Pharmacogenetics and Pharmacogenomics Knowledge Base(PharmGKB). 
      The "active component-target-MF" network was constructed and analyzed 
      by Cytoscape 3.8.1. The protein-protein interaction(PPI) network was constructed 
      by STRING. The Gene Ontology(GO) biological process enrichment analysis was 
      performed by CluoGO plug-in. Kyoto Encyclopedia of Genes and Genomes(KEGG) 
      signaling pathway enrichment analysis was performed by R 4.0.2 and Funrich. 
      Subsequently, the inhibitory effect of CF-LS on MF was investigated based on 
      angiotensin Ⅱ(Ang Ⅱ)-induced MF rats. RT-PCR and ELISA were used to verify the 
      effect of CF-LS on the targets of signaling pathways related to vascular 
      endothelial cells predicted by the network pharmacology. Thirty-one active 
      components and 204 potential targets of CF-LS, 4 671 MF-related targets, and 174 
      common targets were obtained. The network analysis showed that the key targets of 
      CF-LS against MF included RAC-alpha serine/threonine-protein kinase(AKT1), 
      transcription factor AP-1(JUN), mitogen-activated protein kinase 1(MAPK1), 
      cellular tumor antigen p53(TP53), transcription factor p65(RELA), and 
      mitogen-activated protein kinase 8(MAPK8). Biological processes mainly involved 
      regulation of blood vessel diameter, regulation of blood vessel endothelial cell 
      migration, cell death in response to oxidative stress, etc. Advanced glycation 
      end products(AGE)-receptor for advanced glycation end products(RAGE) signaling 
      pathway, phosphoinositide 3-kinase(PI3 K)-serine/threonine protein kinase(AKT) 
      signaling pathway, hypoxia-inducible factor-1(HIF-1) signaling pathway, integrin 
      signaling pathway, transforming growth factor-beta(TGF-beta) signaling pathway, etc. 
      were involved in signaling pathway enrichment. Literature retrieval confirmed 
      that some of these signaling pathways were closely related to vascular 
      endothelial cells, including AGE-RAGE, PI3 K-AKT, HIF-1alpha, p53, the transcription 
      factor activator protein-1(AP-1), integrin, p38 MAPK, and TGF-beta. Animal 
      experiments showed that CF-LS inhibited MF induced by Ang Ⅱ in rats by 
      suppressing the expression of RAGE, HIF-1alpha, integrin beta6, and TGF-beta1. The 
      inhibitory effect of CF-LS on MF has the characteristics of multiple components, 
      multiple targets, and multiple pathways. CF-LS can inhibit MF by regulating the 
      activity of vascular endothelial cells in the cardiac microenvironment.
FAU - Wang, Yong
AU  - Wang Y
AD  - Affiliated Hospital of Shandong University of Traditional Chinese Medicine Ji'nan 
      250011, China.
FAU - Wang, Zhen
AU  - Wang Z
AD  - Affiliated Hospital of Shandong University of Traditional Chinese Medicine Ji'nan 
      250011, China.
FAU - Wang, Cheng
AU  - Wang C
AD  - Zaozhuang Municipal Hospital Zaozhuang 277000, China.
FAU - Ma, Du-Fang
AU  - Ma DF
AD  - Affiliated Hospital of Shandong University of Traditional Chinese Medicine Ji'nan 
      250011, China.
LA  - chi
PT  - Journal Article
PL  - China
TA  - Zhongguo Zhong Yao Za Zhi
JT  - Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese 
      materia medica
JID - 8913656
RN  - 0 (Drugs, Chinese Herbal)
SB  - IM
MH  - *Animal Experimentation
MH  - Animals
MH  - *Drugs, Chinese Herbal/pharmacology
MH  - Endothelial Cells
MH  - Fibrosis
MH  - Medicine, Chinese Traditional
MH  - Molecular Docking Simulation
MH  - Network Pharmacology
MH  - Phosphatidylinositol 3-Kinases
MH  - Rats
MH  - Semen
OTO - NOTNLM
OT  - Carthami Flos-Lepidii Semen
OT  - cardiac microenvironment
OT  - drug pair
OT  - myocardial fibrosis
OT  - network pharmacology
OT  - vascular endothelial cell
EDAT- 2022/02/19 06:00
MHDA- 2022/02/22 06:00
CRDT- 2022/02/18 05:55
PHST- 2022/02/18 05:55 [entrez]
PHST- 2022/02/19 06:00 [pubmed]
PHST- 2022/02/22 06:00 [medline]
AID - 10.19540/j.cnki.cjcmm.20210929.401 [doi]
PST - ppublish
SO  - Zhongguo Zhong Yao Za Zhi. 2022 Feb;47(3):753-763. doi: 
      10.19540/j.cnki.cjcmm.20210929.401.