acanthoic-acid and Edema

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.

Topics: Acute Lung Injury; Animals; Anti-Inflammatory Agents; Bronchoalveolar Lavage Fluid; Diterpenes; Edema; Interleukin-1beta; Interleukin-6; Lipopolysaccharides; Liver X Receptors; Lung; Macrophages, Alveolar; Male; Mice; Mice, Inbred BALB C; NF-kappa B; Orphan Nuclear Receptors; Peroxidase; Tumor Necrosis Factor-alpha

Syntheses and excellent anti-inflammatory effects of a series of novel acanthoic acid analogs are reported. In particular, the mechanistic basis for their anti-inflammatory effects is also described.

Topics: Abietanes; Animals; Anti-Inflammatory Agents, Non-Steroidal; Cells, Cultured; Cyclooxygenase Inhibitors; Diterpenes; Edema; Models, Chemical; Nitric Oxide