Isoorientin protects lipopolysaccharide-induced acute lung injury in mice via modulating Keap1/Nrf2-HO-1 and NLRP3 inflammasome pathways.

Abstract

Acute lung injury (ALI) is a pulmonary disease with high mortality. The present study investigated the protective effect of isoorientin (ISO) on lipopolysaccharide (LPS)-induced ALI compared with Thalictrum minus L. (TML). The experimental ALI was achieved by LPS via endotracheal drip, ISO and TML (40 mg/kg) were administered orally 1 h prior to LPS. ISO treatment significantly protected mice from ALI and exhibited similar efficacy as TML. Administration of ISO markedly corrected weight loss and improved lung pathological damage caused by LPS. Meanwhile, a decline of lung wet to dry weight (W/D) ratios and total protein in bronchoalveolar fluid (BALF) demonstrated that ISO mitigated pulmonary edema and vascular leakage of ALI mice. Moreover, ISO also signally decreased oxidative stress and suppressed the content of interleukin-6 (IL-6) in BALF. Additionally, ISO significantly promoted the expression of nuclear factor E2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1) and down-regulated kelch-like ECH-associated protein 1 (Keap1). Simultaneously, it suppressed the over-expression of NOD-, LRR- and pyrin domain-containing 3 (NLRP3), caspase-1, apoptosis-associated speck-like protein containing a CARD (ASC) and pro-inflammatory cytokines interleukin IL-1β (pro-IL-1β), and inhibited the expression of apoptotic related proteins induced by LPS challenge. Meanwhile, the results of molecular docking indicated the potential ability of ISO as a ligand binding with proteins Keap1, NLRP3 and cleaved-caspase-3 as well. These findings demonstrated that ISO might be one of the bioactive components of TML in the treatment of ALI and provided a rationale for future clinical applications and potential protective strategies for ALI.

• Authors: Lu Zhang, Xiao-Zhou Zhu, Rentsen Badamjav, Jia-Zhi Zhang, Jun-Ping Kou, Bo-Yang Yu, Fang Li
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 917 Pg. 174748 (Feb 15 2022) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 34999086 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 Elsevier B.V. All rights reserved.

Chemical References

• KEAP1 protein, human
• Kelch-Like ECH-Associated Protein 1

Topics

• Kelch-Like ECH-Associated Protein 1