PMID- 33708129
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210313
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 12
DP  - 2021
TI  - Ginsenoside Rc Ameliorates Endothelial Insulin Resistance via Upregulation of 
      Angiotensin-Converting Enzyme 2.
PG  - 620524
LID - 10.3389/fphar.2021.620524 [doi]
LID - 620524
AB  - Type 2 diabetes mellitus (T2DM) is a major health concern which may cause 
      cardiovascular complications. Insulin resistance (IR), regarded as a hallmark of 
      T2DM, is characterized by endothelial dysfunction. Ginsenoside Rc is one of the 
      main protopanaxadiol-type saponins with relatively less research on it. Despite 
      researches confirming the potent anti-inflammatory and antioxidant activities of 
      ginsenoside Rc, the potential benefits of ginsenoside Rc against vascular 
      complications have not been explored. In the present study, we investigated the 
      effects of ginsenoside Rc on endothelial IR and endothelial dysfunction with its 
      underlying mechanisms using high glucose- (HG-) cultured human umbilical vein 
      endothelial cells (HUVECs) in vitro and a type 2 diabetic model of db/db mice in 
      vivo. The results showed that ginsenoside Rc corrected the imbalance of vasomotor 
      factors, reduced the production of Ang (angiotensin) II, and activated 
      angiotensin-converting enzyme 2 (ACE2)/Ang-(1-7)/Mas axis in HG-treated HUVECs. 
      Besides, ginsenoside Rc improved the impaired insulin signaling pathway and 
      repressed oxidative stress and inflammatory pathways which constitute key factors 
      leading to IR. Interestingly, the effects of ginsenoside Rc on HG-induced HUVECs 
      were abolished by the selective ACE2 inhibitor MLN-4760. Furthermore, ginsenoside 
      Rc exhibited anti-inflammatory as well as antioxidant properties and ameliorated 
      endothelial dysfunction via upregulation of ACE2 in db/db mice, which were 
      confirmed by the application of MLN-4760. In conclusion, our findings reveal a 
      novel action of ginsenoside Rc and demonstrate that ginsenoside Rc ameliorated 
      endothelial IR and endothelial dysfunction, at least in part, via upregulation of 
      ACE2 and holds promise for the treatment of diabetic vascular complications.
CI  - Copyright (c) 2021 Wang, Fu, Xue, Lu, Li, Yu, Yu, Xu and Sui.
FAU - Wang, Yaozhen
AU  - Wang Y
AD  - Department of Pharmacology, School of Pharmaceutical Sciences, Jilin University, 
      Changchun, China.
FAU - Fu, Wenwen
AU  - Fu W
AD  - Department of Pharmacology, School of Pharmaceutical Sciences, Jilin University, 
      Changchun, China.
FAU - Xue, Yan
AU  - Xue Y
AD  - Department of Pharmacology, School of Pharmaceutical Sciences, Jilin University, 
      Changchun, China.
AD  - Department of Burn Surgery, The First Hospital of Jilin University, Changchun, 
      China.
FAU - Lu, Zeyuan
AU  - Lu Z
AD  - Department of Pharmacology, School of Pharmaceutical Sciences, Jilin University, 
      Changchun, China.
FAU - Li, Yuangeng
AU  - Li Y
AD  - Department of Pharmacology, School of Pharmaceutical Sciences, Jilin University, 
      Changchun, China.
FAU - Yu, Ping
AU  - Yu P
AD  - Department of Pharmacology, School of Pharmaceutical Sciences, Jilin University, 
      Changchun, China.
FAU - Yu, Xiaofeng
AU  - Yu X
AD  - Department of Pharmacology, School of Pharmaceutical Sciences, Jilin University, 
      Changchun, China.
FAU - Xu, Huali
AU  - Xu H
AD  - Department of Pharmacology, School of Pharmaceutical Sciences, Jilin University, 
      Changchun, China.
FAU - Sui, Dayun
AU  - Sui D
AD  - Department of Pharmacology, School of Pharmaceutical Sciences, Jilin University, 
      Changchun, China.
LA  - eng
PT  - Journal Article
DEP - 20210223
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC7940763
OTO - NOTNLM
OT  - ACE2
OT  - MLN-4760
OT  - endothelial cells
OT  - endothelial dysfunction
OT  - ginsenoside Rc
OT  - insulin resistance
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/03/13 06:00
MHDA- 2021/03/13 06:01
PMCR- 2021/02/23
CRDT- 2021/03/12 07:13
PHST- 2020/10/23 00:00 [received]
PHST- 2021/01/11 00:00 [accepted]
PHST- 2021/03/12 07:13 [entrez]
PHST- 2021/03/13 06:00 [pubmed]
PHST- 2021/03/13 06:01 [medline]
PHST- 2021/02/23 00:00 [pmc-release]
AID - 620524 [pii]
AID - 10.3389/fphar.2021.620524 [doi]
PST - epublish
SO  - Front Pharmacol. 2021 Feb 23;12:620524. doi: 10.3389/fphar.2021.620524. 
      eCollection 2021.