The effects of Isoorientin on modulating Keap1/Nrf2-HO-1 and NLRP3 inflammasome pathways in acute lung injury
- VernacularTitle:Уушгины хурц гэмтлийн үед Keap1/Nrf2-HO-1 болон NLRP3 инфламмасом дохионы замд изоориентины үзүүлэх нөлөө
- Author:
Badamjav Rentsen
1
;
Enkhjargal Naranchimeg
1
;
Myagmar Narankhuu
1
;
Batchuluun Tsolmon
1
;
Fang Li
2
Author Information
1. Mongolian University of Pharmaceutical Sciences
2. China Pharmaceutical University, Nanjing, Jiangsu
- Publication Type:Journal Article
- Keywords:
Isoorientin;
Acute lung injury Inflammation;
Signaling pathways
- From:
Mongolian Pharmacy and Pharmacology
2024;24(1):39-43
- CountryMongolia
- Language:Mongolian
-
Abstract:
The process of ALI is associated with excessive pulmonary inflammation as undue activation of immune cells including macrophages and neutrophile granulocytes and subsequently increased cytokines such as interleukin 6 (IL-6) contribute to severe tissue damage and irreversible pulmonary pathological changes. NOD-, LRR- and pyrin domain-containing 3 (NLRP3) inflammasome is a cytosolic receptor consisting of upstream sensor protein NLRP3, adaptor protein apoptosis-associated speck-like protein containing a CARD (ASC) and the effector protein caspase-1. Nuclear factor E2-related factor 2 (Nrf2) is a transcription factor that neutralizes oxidative stress via initiating antioxidant response element-driven gene transcription.
Nrf2 is suppressed by kelch-like ECH-associated protein 1 (Keap1) under physiological conditions, while Nrf2 dissociates from Keap1, stabilizes and accumulates in the nucleus with stimulation of oxidative stress. Thereafter, heme oxygenase 1 (HO-1) a downstream target gene of Nrf2 is activated to catalyze various detoxification reactions and exert anti-oxidative capacity.
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.
- Full text:2025051101335971066MPPJ-2024-24(1)-39-43.pdf
