title: 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.affiliation: Department of Thoracic Surgery, The 2nd Affiliated Hospital of Harbin Medical University, Harbin 150086, China.
authors.forename: Wang
authors.initials: W
authors.lastname: Qiushi
authors.affiliation: Department of Thoracic Surgery, The 2nd Affiliated Hospital of Harbin Medical University, Harbin 150086, China.
authors.forename: Li
authors.initials: L
authors.lastname: Guanghua
authors.affiliation: Department of Thoracic Surgery, The 2nd Affiliated Hospital of Harbin Medical University, Harbin 150086, China. Electronic address: xvguangquanlb@163.com.
authors.forename: Xu
authors.initials: X
authors.lastname: Guangquan
mesh_terms: D055371:Acute Lung Injury / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001992:Bronchoalveolar Lavage Fluid; D004224:Diterpenes / Q000494:pharmacology* / Q000627:therapeutic use; D004487:Edema / Q000150:complications; D053583:Interleukin-1beta / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000009:adverse effects*; D000071518:Liver X Receptors; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D057093:Orphan Nuclear Receptors / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D000893:Anti-Inflammatory Agents; D004224:Diterpenes; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D000071518:Liver X Receptors; D016328:NF-kappa B; C000605214:Nr1h3 protein, mouse; D057093:Orphan Nuclear Receptors; D014409:Tumor Necrosis Factor-alpha; C099958:acanthoic acid; D009195:Peroxidase
keywords: Acanthoic acid; Acute lung injury; LPS; LXRα; NF-κB