Acanthoic acid ameliorates lipopolysaccharide-induced acute lung injury.

Abstract

Acanthoic acid, a pimaradiene diterpene isolated from Acanthopanax koreanum, has been reported to have anti-inflammatory activities. However, the effects of acanthoic acid on LPS-induced acute lung injury have not been reported. The purpose of this study was to investigate the protective effect of acanthoic acid on LPS-induced ALI and to clarify the possible anti-inflammatory mechanisms. In vivo, an LPS-induced ALI model in mice was used to assess the protective effects of acanthoic acid on ALI. Meanwhile, mouse alveolar macrophages MH-S were stimulated with LPS in the presence or absence of acanthoic acid. The expressions of TNF-α, IL-6 and IL-1β were measured by ELISA. LXRα and NF-κB expression were detected by Western blot analysis. The results showed that acanthoic acid downregulated LPS-induced TNF-α, IL-6 and IL-1β production in BALF. MPO activity and lung wet-to-dry ratio were also inhibited by acanthoic acid. In addition, acanthoic acid attenuated lung histopathologic changes. In vitro, acanthoic acid inhibited inflammatory cytokines TNF-α, IL-6 and IL-1β production and NF-κB activation in LPS-stimulated alveolar macrophages. Acanthoic acid was found to up-regulated the expression of LXRα. The inhibition of acanthoic acid on LPS-induced cytokines and NF-κB activation can be abolished by LXRα siRNA. In conclusion, our results suggested that the protective effect of acanthoic acid on LPS-induced ALI was due to its ability to activate LXRα, thereby inhibiting LPS-induced inflammatory response.

• Authors: Wang Qiushi, Li Guanghua, Xu Guangquan
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 750 Pg. 32-8 (Mar 05 2015) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 25620130 (Publication Type: Journal Article)
• Copyright: Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Diterpenes
• Interleukin-1beta
• Interleukin-6
• Lipopolysaccharides
• Liver X Receptors
• NF-kappa B
• Nr1h3 protein, mouse
• Orphan Nuclear Receptors
• Tumor Necrosis Factor-alpha
• acanthoic acid
• Peroxidase

Topics

• Acute Lung Injury (complications, drug therapy, metabolism, pathology)
• Animals
• Anti-Inflammatory Agents (pharmacology, therapeutic use)
• Bronchoalveolar Lavage Fluid
• Diterpenes (pharmacology, therapeutic use)
• Edema (complications)
• Interleukin-1beta (biosynthesis)
• Interleukin-6 (biosynthesis)
• Lipopolysaccharides (adverse effects)
• Liver X Receptors
• Lung (drug effects, metabolism, pathology)
• Macrophages, Alveolar (drug effects, metabolism)
• Male
• Mice
• Mice, Inbred BALB C
• NF-kappa B (metabolism)
• Orphan Nuclear Receptors (metabolism)
• Peroxidase (metabolism)
• Tumor Necrosis Factor-alpha (biosynthesis)