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

ABSTRACT: 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 Heterodermia hypoleuca. 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 I?B, extracellular signal-regulated kinases (ERK) and nuclear factor kappa B (NF?B) 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/NF?B signaling pathway, demonstrating its potential therapeutic value for treating inflammatory diseases.

SUBMITTER: Mun SK

PROVIDER: S-EPMC7582958 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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

Mun Seul-Ki SK Kang Kyung-Yun KY Jang Ho-Yeol HY Hwang Yun-Ho YH Hong Seong-Gyeol SG Kim Su-Jin SJ Cho Hyun-Wook HW Chang Dong-Jo DJ Hur Jae-Seoun JS Yee Sung-Tae ST

International journal of molecular sciences 20200925 19

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 <i>Heterodermia hypoleuca</i>. The results confirmed that atraric acid could regulate induced pro-inflammatory cytokine, nitric oxide, prostaglandin E2, induced nitric oxide synthase and cyclooxygena ...[more]

PMID: 32992840

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Project description:ContextAjuga ovalifolia Bur. et Franch. var. calantha (Diels) C. Y. Wu et C. Chen (Labiatae), a traditional Chinese medicine, has been used to treat several inflammatory diseases.ObjectiveTo assess the anti-inflammatory activity of ajudecumin A isolated from Ajuga ovalifolia var. calantha, and its possible mechanisms.Materials and methodsLipopolysaccharide (LPS, 0.5 μg/mL)-stimulated RAW264.7 macrophages were used to assess the anti-inflammatory activity of ajudecumin A (1-40 μM) in vitro. Nitric oxide levels were evaluated by Griess reagent. The mRNA levels of iNOS, COX-2, TNF-α, IL-1β and IL-6 were determined using qRT-PCR. Phosphorylation of ERK, JNK, p38 MAPK and IκBα were detected by western Blot. To further assess the anti-inflammatory of ajudecumin A in vivo, mice were oral treated with ajudecumin A (10 mg/kg) or dexamethasone (0.25 mg/kg, positive control) for 5 days before administration of carrageenan or xylene. Paw and ear edema were then measured, respectively.ResultsAjudecumin A (10-40 μM) decreased LPS-induced nitric oxide production with an IC50 value of 16.19 μM. Ajudecumin A (20 and 40 μM) also attenuated cell spreading and formation of pseudopodia-like structures, and decreased the mRNA levels of iNOS (55.23-67.04%, p < 0.001), COX-2 (57.58-70.25%, p < 0.001), TNF-α (53.75-58.94%, p < 0.01-0.001), IL-1β (79.41-87.85%, p < 0.001) and IL-6 (54.26-80.52%, p < 0.01-0.001) in LPS-activated RAW264.7 cells. Furthermore, ajudecumin A suppressed LPS-induced phosphorylation of ERK, p38 MAPK, and IκBα, as well as IκBα degradation (p < 0.05-0.001). Finally, ajudecumin A (10 mg/kg) attenuated carrageenan- and xylene-induced inflammation in mice by about 28 and 24%, respectively.Discussion and conclusionsAjudecumin A exhibited a potent anti-inflammatory activity in vitro and in vivo through inhibition on NF-κB and ERK/p38 MAPK pathways, suggesting that ajudecumin A may be potentially developed as a lead compound in anti-inflammatory drug discovery.

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

Publications

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

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