Dataset Information

An Algal Metabolite-Based PPAR-? Agonist Displayed Anti-Inflammatory Effect via Inhibition of the NF-?B Pathway.

ABSTRACT: In our previous study, a synthetic compound, (+)-(R,E)-6a1, that incorporated the key structures of anti-inflammatory algal metabolites and the endogenous peroxisome proliferator-activated receptor ? (PPAR-?) ligand 15-deoxy-?^12,14-prostaglandin J₂ (15d-PGJ₂), exerted significant PPAR-? transcriptional activity. Because PPAR-? expressed in macrophages has been postulated as a negative regulator of inflammation, this study was designed to investigate the anti-inflammatory effect of the PPAR-? agonist, (+)-(R,E)-6a1. Compound (+)-(R,E)-6a1 displayed in vitro anti-inflammatory activity in lipopolysaccharides (LPS)-stimulated murine RAW264.7 macrophages. Compound (+)-(R,E)-6a1 suppressed the expression of proinflammatory factors, such as nitric oxide (NO), inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), and tumor necrosis factor-? (TNF-?), possibly by the inhibition of the nuclear factor-?B (NF-?B) pathway. In macrophages, (+)-(R,E)-6a1 suppressed LPS-induced phosphorylation of NF-?B, inhibitor of NF-?B ? (I?B?), and I?B kinase (IKK). These results indicated that PPAR-? agonist, (+)-(R,E)-6a1, exerts anti-inflammatory activity via inhibition of the NF-?B pathway.

SUBMITTER: Ju Z

PROVIDER: S-EPMC6627743 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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An Algal Metabolite-Based PPAR-γ Agonist Displayed Anti-Inflammatory Effect via Inhibition of the NF-κB Pathway.

Ju Zhiran Z Su Mingzhi M Li Dandan D Hong Jongki J Im Dong-Soon DS Kim Suhkmann S Kim Eun La E Jung Jee H JH

Marine drugs 20190530 6

In our previous study, a synthetic compound, (+)-(R,E)-6a1, that incorporated the key structures of anti-inflammatory algal metabolites and the endogenous peroxisome proliferator-activated receptor γ (PPAR-γ) ligand 15-deoxy-∆12,14-prostaglandin J2 (15d-PGJ2), exerted significant PPAR-γ transcriptional activity. Because PPAR-γ expressed in macrophages has been postulated as a negative regulator of inflammation, this study was designed to inve ...[more]

PMID: 31151271

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Project description:Progressive liver fibrosis, caused by chronic viral infection and metabolic disorders, results in the development of cirrhosis and hepatocellular carcinoma. However, no antifibrotic therapies have been approved to date. In our previous study, adeno‑associated virus (AAV) short hairpin RNAs (shRNAs) targeting hepatitis B virus (HBV) and transforming growth factor (TGF)‑β administration could persistently inhibit HBV replication and concomitantly prevent liver fibrosis. However, the differentially expressed proteins and critical regulatory networks of AAV‑shRNA treatment remain unclear. Accordingly, in the present study, we aimed to analyze differentially expressed proteins in the liver of AAV‑shRNA‑treated mice with HBV infection and liver fibrosis using isobaric tags for relative and absolute quantitation (iTRAQ)‑based quantitative proteomics and to elucidate the underlying antifibrotic mechanisms. In total 2,743 proteins were recognized by iTRAQ‑based quantitative proteomics analysis. Gene Ontology analysis revealed that the differentially expressed proteins mostly participated in peptide metabolism in the biological process category, cytosolic ribosomes in the cell component category, and structural constituents of ribosomes in the molecular function category. Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated that oxidative stress and the peroxisome proliferator‑activated receptor (PPAR) signaling pathway were activated after treatment. Verification studies revealed that AAV‑shRNAs inhibited hepatic stellate cell activation and inflammation by suppressing nuclear factor‑κB p65 phosphorylation and α‑smooth muscle actin expression via upregulation of PPAR‑γ. Hepatocytes steatosis was also decreased by activating the PPAR signaling pathway and improving lipid metabolism. The expression level of TGF‑β was decreased due to upregulation of PPAR‑γ expression and direct inhibition using AAV‑shRNA targeting TGF‑β. TGF‑β‑induced oxidative stress was suppressed by increasing glutathione S‑transferase Pi 1 and reducing peroxiredoxin 1. Collectively, the present results indicated that AAV‑shRNAs were effective in modulating liver fibrosis by reducing oxidative stress, inflammation and activating the PPAR signaling pathway.

Dataset Information

An Algal Metabolite-Based PPAR-? Agonist Displayed Anti-Inflammatory Effect via Inhibition of the NF-?B Pathway.

Publications

An Algal Metabolite-Based PPAR-γ Agonist Displayed Anti-Inflammatory Effect via Inhibition of the NF-κB Pathway.

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