Aqueous Extract of Descuraniae Semen Attenuates Lipopolysaccharide-Induced Inflammation and Apoptosis by Regulating the Proteasomal Degradation and IRE1α-Dependent Unfolded Protein Response in A549 Cells.

Abstract

Background:

Lipopolysaccharide (LPS)-induced acute lung injury (ALI) induces endoplasmic reticulum stress, unfolded protein response (UPR), apoptosis, and inflammation. Inositol-requiring enzyme 1 (IRE1)-α is important for adaptive and apoptotic UPR determination during ER stress. The aqueous extract of Descuraniae Semen (AEDS) is reported to be a safe and effective herb for the treatment of pulmonary edema as it shows anti-inflammatory activities.

Methods:

We investigated the effects of AEDS on LPS-induced ALI in A549 cells with respect to the regulation of IRE1α-dependent UPR, proteasomal degradation, mitochondrial membrane potential (MtMP), inflammation, and apoptosis.

Results:

AEDS attenuated ER stress by regulating the proteasomal degradation. LPS induced ER stress [binding immunoglobulin protein (BiP), phosphorylated IRE1α, sliced X-box binding protein 1 [XBP1s], phosphorylated cJUN NH2-terminal kinase (pJNK), B-cell lymphoma (Bcl)-2-associated X (Bax), Bcl-2], inflammation (nucleus factor-kappa B (NF-κB) p65 nuclear translocation, nucleus NF-κB, pro-inflammatory cytokines] and apoptosis [C/EBP homologous protein (CHOP), cytochrome c, caspase-8, and caspase-6, and TUNEL] were significantly attenuated by AEDS treatment in A549 cells. AEDS prevents LPS-induced decreased expression of MtMP in A549 cells.

Conclusions:

AEDS attenuated LPS-induced inflammation and apoptosis by regulating proteasomal degradation, promoting IRE1α-dependent adaptive UPR, and inhibiting IRE1α-dependent apoptotic UPR. Moreover, IRE1α-dependent UPR plays a pivotal role in the mechanisms of LPS-induced ALI. Based on these findings, AEDS is suggested as a potential therapeutic option for treating patients with ALI.

• Authors: Po-Chun Hsieh, Chung-Kan Peng, Guan-Ting Liu, Chan-Yen Kuo, I-Shiang Tzeng, Ming-Chieh Wang, Chou-Chin Lan, Kun-Lun Huang
• Journal: Frontiers in immunology (Front Immunol) Vol. 13 Pg. 916102 ( 2022) ISSN: 1664-3224 [Electronic] Switzerland
• PMID: 35812413 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 Hsieh, Peng, Liu, Kuo, Tzeng, Wang, Lan and Huang.

Chemical References

• Lipopolysaccharides
• NF-kappa B
• ERN1 protein, human
• Protein Serine-Threonine Kinases
• Endoribonucleases

Topics

• A549 Cells
• Acute Lung Injury (chemically induced, drug therapy)
• Apoptosis
• Endoribonucleases (metabolism)
• Humans
• Inflammation (chemically induced, drug therapy)
• Lipopolysaccharides (pharmacology)
• NF-kappa B (metabolism)
• Protein Serine-Threonine Kinases
• Semen (metabolism)
• Unfolded Protein Response