PMID- 34411833
OWN - NLM
STAT- MEDLINE
DCOM- 20210929
LR  - 20210929
IS  - 1618-095X (Electronic)
IS  - 0944-7113 (Linking)
VI  - 91
DP  - 2021 Oct
TI  - Cardioprotective effect of icariin against myocardial fibrosis and its molecular 
      mechanism in diabetic cardiomyopathy based on network pharmacology: Role of ICA 
      in DCM.
PG  - 153607
LID - S0944-7113(21)00149-5 [pii]
LID - 10.1016/j.phymed.2021.153607 [doi]
AB  - BACKGROUND: Diabetic cardiomyopathy (DCM) is one of the most severe symptoms of 
      diabetes. It continues to be a major clinical problem, but our knowledge of its 
      molecular mechanisms and effective treatments are limited. Traditional Chinese 
      medicine has been shown to be a pool of novel drugs for diabetes. PURPOSE: 
      Herein, we aim to define the molecular mechanism of icariin (ICA), an extract 
      from a traditional Chinese medicine herb, in protecting cardiac structures and 
      restoring cardiac functions of in a rat model of type 2 diabetes mellitus (T2DM). 
      STUDY DESIGN AND METHODS: Candidate genes related to T2DM were identified through 
      bioinformatics screening and their interactions were constructed by molecule 
      docking technique, followed by pathway enrichment analyses of their cellular 
      functions. A T2DM rat model was then established to evaluate the effects of ICA 
      on cardiac structures, myocardial fibrosis, and cellular Ca(2+) inflow, as 
      reflected by HE and Masson staining, qRT-PCR and Western blot determination of 
      related genes, and measurement of the L-type Ca(2+) current. RESULTS: Four 
      potential target genes (Jun, p65, NOS3, and PDE5A) were identified. ICA 
      ameliorated the structural damage and myocardial fibrosis in T2DM rats. 
      Intracellular Ca2+ hyperactivities and dysfunction in myocardium of T2DM rats 
      were also repressed by ICA treatment. Furthermore, ICA-induced inhibition of Jun 
      and p65 ameliorated the irregular collagen metabolism and myocardial fibrosis. 
      NOS3, PDE5A and the related sGC-cGMP-PKG signaling pathway mediated the 
      ICA-induced improvement of intracellular Ca(2+) inflow. CONCLUSION: In 
      conclusion, these results demonstrate the regulatory roles of potential target 
      genes in DCM and suggest ICA as an effective treatment of DCM by targeting these 
      genes specifically.
CI  - Copyright (c) 2021. Published by Elsevier GmbH.
FAU - Zhang, Liping
AU  - Zhang L
AD  - Department of Cardiology, The First Hospital of Jilin University, Changchun 
      130021, PR China. Electronic address: xyd0424@jlu.edu.cn.
FAU - Wang, Shudong
AU  - Wang S
AD  - Department of Cardiology, The First Hospital of Jilin University, Changchun 
      130021, PR China. Electronic address: shudong_wang@jlu.edu.cn.
FAU - Li, Yuying
AU  - Li Y
AD  - Department of Hematology, The First Hospital of Jilin University, Changchun 
      130021, PR China. Electronic address: lyying1001@jlu.edu.cn.
FAU - Wang, Yonggang
AU  - Wang Y
AD  - Department of Cardiology, The First Hospital of Jilin University, Changchun 
      130021, PR China. Electronic address: wangyg1982@jlu.edu.cn.
FAU - Dong, Chunzhe
AU  - Dong C
AD  - Department of Abdominal Ultrasound, The First Hospital of Jilin University, 
      Changchun 130021, PR China. Electronic address: dongcz@jlu.edu.cn.
FAU - Xu, Hui
AU  - Xu H
AD  - Department of Echocardiography, The First Hospital of Jilin University, Changchun 
      130021, PR China. Electronic address: x_hui@jlu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20210524
PL  - Germany
TA  - Phytomedicine
JT  - Phytomedicine : international journal of phytotherapy and phytopharmacology
JID - 9438794
RN  - 0 (Cardiotonic Agents)
RN  - 0 (Flavonoids)
RN  - VNM47R2QSQ (icariin)
SB  - IM
MH  - Animals
MH  - Cardiotonic Agents/*pharmacology
MH  - *Diabetes Mellitus, Experimental/drug therapy/pathology
MH  - *Diabetes Mellitus, Type 2/pathology
MH  - *Diabetic Cardiomyopathies/drug therapy
MH  - Fibrosis
MH  - Flavonoids/*pharmacology
MH  - Myocardium/pathology
MH  - Rats
OTO - NOTNLM
OT  - Ca(2+) inflow
OT  - Cardiac dysfunction
OT  - Diabetic cardiomyopathy
OT  - Icariin
OT  - Myocardial fibrosis
OT  - Network pharmacology
EDAT- 2021/08/20 06:00
MHDA- 2021/09/30 06:00
CRDT- 2021/08/19 20:20
PHST- 2021/01/11 00:00 [received]
PHST- 2021/05/13 00:00 [revised]
PHST- 2021/05/18 00:00 [accepted]
PHST- 2021/08/20 06:00 [pubmed]
PHST- 2021/09/30 06:00 [medline]
PHST- 2021/08/19 20:20 [entrez]
AID - S0944-7113(21)00149-5 [pii]
AID - 10.1016/j.phymed.2021.153607 [doi]
PST - ppublish
SO  - Phytomedicine. 2021 Oct;91:153607. doi: 10.1016/j.phymed.2021.153607. Epub 2021 
      May 24.