Protective Effects of Tyrosol against LPS-Induced Acute Lung Injury via Inhibiting NF-κB and AP-1 Activation and Activating the HO-1/Nrf2 Pathways

• Published in: Biological & pharmaceutical bulletin 2017/05/01, Vol.40(5), pp.583-593
• Main Authors: Wang, Wen-chen, Xia, Yan-min, Yang, Bo, Su, Xiang-ni, Chen, Jia-kuan, Li, Wei, Jiang, Tao
• Format: Article
• Language: English
• Subjects: Activation; Activation analysis; activator protein (AP)-1; Activator protein 1; acute lung injury (ALI); Acute Lung Injury - prevention & control; Animals; Anti-inflammatory agents; Cells, Cultured; Heme; heme oxygenase (HO)-1; Heme Oxygenase-1 - physiology; Inflammation; Lipopolysaccharides; Lipopolysaccharides - pharmacology; Lungs; Male; Mice; Mice, Inbred C57BL; NF-E2-Related Factor 2 - physiology; NF-kappa B - antagonists & inhibitors; nuclear factor (NF)-κB; nuclear factor erythroid-2 related factor 2(Nrf2); Oxygenase; Permeability; Peroxidase - metabolism; Phenylethyl Alcohol - analogs & derivatives; Phenylethyl Alcohol - pharmacology; Pretreatment; Rodents; Signal Transduction - drug effects; Signal Transduction - physiology; Transcription Factor AP-1 - antagonists & inhibitors; Transcription factors; Tyrosol; tyrosol(Tyr)
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.b16-00756

Tyrosol (Tyr) is a natural antioxidant that displays anti-oxidant and anti-inflammatory properties. The present study aimed to investigate the effect and mechanism of Tyr on lipopolysaccharide (LPS)-induced acute lung injury (ALI). In a mouse model, we found that pretreatment with Tyr significantly improved survival rate, attenuated lung permeability, ameliorated histopathological alterations, reduced expression of the inflammatory mediators and improved expression of the antioxidant enzyme. Further study revealed that Tyr markedly inhibited nuclear factor-κB (NF-κB) and activator protein-1 (AP-1) activation at both in vivo and in vitro levels. To investigate the underlying mechanism, we examined the impact of Tyr on the heme oxygenase (HO)-1/nuclear factor erythroid-2 related factor 2 (Nrf2) pathway in vivo and in vitro. The results showed that Tyr significantly improved the expression of HO-1 and the activation of Nrf2. This study offers novel evidence to support the efficacy of Tyr against ALI, which helps to clarify the underlying causes of the therapeutic effects behind Tyr.