• Users Online: 338
  • Print this page
  • Email this page
Year : 2022  |  Volume : 65  |  Issue : 4  |  Page : 187-198

18β-Glycyrrhetinic acid ameliorates endoplasmic reticulum stress-induced inflammation in pulmonary arterial hypertension through PERK/eIF2α/NF-κB signaling

1 Department of Pharmacology, College of Pharmacy, Ningxia Medical University, Yinchuan, China
2 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
3 Pediatric Intensive Care Unit, General Hospital of Ningxia Medical University, Yinchuan, China
4 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

Correspondence Address:
Dr. Fang Zhao
General Hospital of Ningxia Medical University, 804 Shengli Street, Yinchuan 750004
Dr. Ru Zhou
Department of Pharmacology, College of Pharmacy, Ningxia Medical University, 1160 Shengli Street, Yinchuan 750004
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0304-4920.354801

Rights and Permissions

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/eIF2α/NF-κB signaling pathway. 18β-Glycyrrhetinic acid (18β-GA) has been found efficacious for attenuating PAH through its anti-remodeling effects in our previous research and it remains unclear whether 18β-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 18β-GA administration in vivo. Moreover, 18β-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 18β-GA could significantly reduce the accumulation of misfolded protein in rat lung tissue, inhibit ERS activation, reduce the expression of GRP78, p-PERK, p-eIF2α, and p-NF-κB p65, and increase IκB protein expression. 18β-GA could inhibit the migration of NF-κB into the nucleus, reduce the contents of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and monocyte chemoattractant protein-1 (MCP-1) in the culture supernatant of HPASMCs, and reduce GRP78, p-PERK, p-eIF2α, p-NF-κB p65, TNF-α, IL-6, and MCP-1 protein expression, increase IκB protein expression in HPASMCs. According to what we observed, this study indicated that 18β-GA could treat PAH, which is related to the inhibition of PERK/eIF2α/NF-κB signaling pathway.

Print this article     Email this article
 Next article
 Previous article
 Table of Contents

 Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
 Citation Manager
 Access Statistics
 Reader Comments
 Email Alert *
 Add to My List *
 * Requires registration (Free)

 Article Access Statistics
    PDF Downloaded123    
    Comments [Add]    

Recommend this journal