PMID- 36073567
OWN - NLM
STAT- MEDLINE
DCOM- 20220909
LR  - 20220916
IS  - 0304-4920 (Print)
IS  - 0304-4920 (Linking)
VI  - 65
IP  - 4
DP  - 2022 Jul-Aug
TI  - 18beta-Glycyrrhetinic acid ameliorates endoplasmic reticulum stress-induced 
      inflammation in pulmonary arterial hypertension through PERK/eIF2alpha/NF-kappaB 
      signaling.
PG  - 187-198
LID - 10.4103/0304-4920.354801 [doi]
AB  - Endoplasmic reticulum stress (ERS)-induced inflammation participates in the 
      occurrence of pulmonary arterial hypertension (PAH) by promoting pulmonary 
      vascular remodeling, which involved in the activation of PERK/eIF2alpha/NF-kappaB 
      signaling pathway. 18beta-Glycyrrhetinic acid (18beta-GA) has been found efficacious 
      for attenuating PAH through its anti-remodeling effects in our previous research 
      and it remains unclear whether 18beta-GA has an effect on the remodeling caused by 
      ERS-induced inflammation. In this study, we made observations in 
      monocrotaline-induced PAH rats and found improvement of hemodynamic and 
      histopathological parameters, decreases in the right ventricular hypertrophy 
      index, and alleviation of pulmonary vascular remodeling after 18beta-GA 
      administration in vivo. Moreover, 18beta-GA could significantly inhibit the 
      proliferation and DNA synthesis of human pulmonary arterial smooth muscle cells 
      (HPASMCs) induced by platelet-derived growth factor BB. At the cellular and 
      molecular levels, we found that 18beta-GA could significantly reduce the 
      accumulation of misfolded protein in rat lung tissue, inhibit ERS activation, 
      reduce the expression of GRP78, p-PERK, p-eIF2alpha, and p-NF-kappaB p65, and increase 
      IkappaB protein expression. 18beta-GA could inhibit the migration of NF-kappaB into the 
      nucleus, reduce the contents of tumor necrosis factor-alpha (TNF-alpha), interleukin 
      (IL)-6, and monocyte chemoattractant protein-1 (MCP-1) in the culture supernatant 
      of HPASMCs, and reduce GRP78, p-PERK, p-eIF2alpha, p-NF-kappaB p65, TNF-alpha, IL-6, and 
      MCP-1 protein expression, increase IkappaB protein expression in HPASMCs. According 
      to what we observed, this study indicated that 18beta-GA could treat PAH, which is 
      related to the inhibition of PERK/eIF2alpha/NF-kappaB signaling pathway.
FAU - Wang, Jia-Ling
AU  - Wang JL
AD  - Department of Pharmacology, College of Pharmacy, Ningxia Medical University, 
      Yinchuan, China.
FAU - Liu, Hui
AU  - Liu H
AD  - Department of Pharmacology, College of Pharmacy, Ningxia Medical University, 
      Yinchuan, China.
FAU - Jing, Zhi-Cheng
AU  - Jing ZC
AD  - Department of Cardiology, Peking Union Medical College Hospital, Key Lab of 
      Pulmonary Vascular Medicine, Chinese Academy of Medical Sciences and Peking Union 
      Medical College, Beijing, China.
FAU - Zhao, Fang
AU  - Zhao F
AD  - Pediatric Intensive Care Unit, General Hospital of Ningxia Medical University, 
      Yinchuan, China.
FAU - Zhou, Ru
AU  - Zhou R
AD  - Department of Pharmacology, College of Pharmacy; Key Laboratory of Ningxia 
      Ethnomedicine Modernization, Ministry of Education; Ningxia Characteristic 
      Traditional Chinese Medicine Modernization Engineering Technology Research 
      Center, Ningxia Medical University, Yinchuan, China.
LA  - eng
PT  - Journal Article
PL  - India
TA  - Chin J Physiol
JT  - The Chinese journal of physiology
JID - 7804502
RN  - 0 (Eukaryotic Initiation Factor-2)
RN  - 0 (I-kappa B Proteins)
RN  - 0 (NF-kappa B)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 1449-05-4 (18alpha-glycyrrhetinic acid)
RN  - P540XA09DR (Glycyrrhetinic Acid)
SB  - IM
MH  - Animals
MH  - Endoplasmic Reticulum Stress
MH  - Eukaryotic Initiation Factor-2/metabolism
MH  - *Glycyrrhetinic Acid/analogs & derivatives/pharmacology
MH  - Humans
MH  - I-kappa B Proteins/metabolism
MH  - Inflammation/drug therapy
MH  - *NF-kappa B/metabolism
MH  - *Pulmonary Arterial Hypertension
MH  - Rats
MH  - Signal Transduction
MH  - Tumor Necrosis Factor-alpha
MH  - Vascular Remodeling
OTO - NOTNLM
OT  - 18beta-Glycyrrhetinic acid
OT  - endoplasmic reticulum stress-induced inflammation
OT  - pulmonary arterial hypertension
OT  - remodeling
COIS- None
EDAT- 2022/09/09 06:00
MHDA- 2022/09/11 06:00
CRDT- 2022/09/08 06:13
PHST- 2022/09/08 06:13 [entrez]
PHST- 2022/09/09 06:00 [pubmed]
PHST- 2022/09/11 06:00 [medline]
AID - ChinJPhysiol_2022_65_4_187_354801 [pii]
AID - 10.4103/0304-4920.354801 [doi]
PST - ppublish
SO  - Chin J Physiol. 2022 Jul-Aug;65(4):187-198. doi: 10.4103/0304-4920.354801.