Atraric Acid Exhibits Anti-Inflammatory Effect in Lipopolysaccharide-Stimulated RAW264.7 Cells and Mouse Models

• Published in: International journal of molecular sciences Vol. 21; no. 19; p. 7070
• Main Authors: Mun, Seul-Ki, Kang, Kyung-Yun, Jang, Ho-Yeol, Hwang, Yun-Ho, Hong, Seong-Gyeol, Kim, Su-Jin, Cho, Hyun-Wook, Chang, Dong-Jo, Hur, Jae-Seoun, Yee, Sung-Tae
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.10.2020; MDPI
• Subjects: Acids; Algae; Animal models; Animals; anti-inflammation; Anti-Inflammatory Agents - pharmacology; Ascomycota - chemistry; atraric acid; Cancer; Cell culture; Cyclooxygenase-2; Cytokines; Cytokines - metabolism; Endotoxin shock; Endotoxins; Enzymes; Extracellular signal-regulated kinase; Female; Heterodermia hypoleuca; Hydroxybenzoates - pharmacology; Inflammatory diseases; Kinases; lichen; Lichens; Lipopolysaccharides; Metabolites; Mice; Mice, Inbred BALB C; Mitogen-Activated Protein Kinase Kinases - metabolism; NF-kappa B - metabolism; NF-κB protein; Nitric oxide; Nitric-oxide synthase; NMR; Nuclear magnetic resonance; Peritoneum; Phosphorylation; Physiological aspects; Plant Extracts - pharmacology; Prostaglandin E2; RAW 264.7 Cells; Secondary metabolites; Shock, Septic - chemically induced; Shock, Septic - drug therapy; Signal transduction; Signal Transduction - drug effects; Tumor necrosis factor-TNF; South Korea; endotoxin shock; anti-inflammation; lichen; Heterodermia hypoleuca; atraric acid
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21197070

Lichens, composite organisms resulting from the symbiotic association between the fungi and algae, produce a variety of secondary metabolites that exhibit pharmacological activities. This study aimed to investigate the anti-inflammatory activities of the secondary metabolite atraric acid produced by . The results confirmed that atraric acid could regulate induced pro-inflammatory cytokine, nitric oxide, prostaglandin E2, induced nitric oxide synthase and cyclooxygenase-2 enzyme expression in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Meanwhile, atraric acid downregulated the expression of phosphorylated IκB, extracellular signal-regulated kinases (ERK) and nuclear factor kappa B (NFκB) signaling pathway to exhibit anti-inflammatory effects in LPS-stimulated RAW264.7 cells. Based on these results, the anti-inflammatory effect of atraric acid during LPS-induced endotoxin shock in a mouse model was confirmed. In the atraric acid treated-group, cytokine production was decreased in the peritoneum and serum, and each organ damaged by LPS-stimulation was recovered. These results indicate that atraric acid has an anti-inflammatory effect, which may be the underlying molecular mechanism involved in the inactivation of the ERK/NFκB signaling pathway, demonstrating its potential therapeutic value for treating inflammatory diseases.