An Anti-Inflammatory PPAR-γ Agonist from the Jellyfish-Derived Fungus Penicillium chrysogenum J08NF-4
| Autor: | Mingzhi Su, Jongki Hong, Sen Liu, Hae Young Chung, Jee H. Jung, Shao-Jiang Song |
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| Rok vydání: | 2018 |
| Předmět: |
Agonist
Scyphozoa medicine.drug_class Interleukin-1beta Anti-Inflammatory Agents Nitric Oxide Synthase Type II Pharmaceutical Science Peroxisome proliferator-activated receptor Penicillium chrysogenum 01 natural sciences Cell Line Analytical Chemistry Mice chemistry.chemical_compound Drug Discovery medicine Animals RAW 264.7 Cells Inflammation Pharmacology Meroterpene chemistry.chemical_classification biology Interleukin-6 Tumor Necrosis Factor-alpha 010405 organic chemistry Chemistry Macrophages Organic Chemistry NF-kappa B Transcription Factor RelA biology.organism_classification Molecular biology 0104 chemical sciences PPAR gamma 010404 medicinal & biomolecular chemistry Complementary and alternative medicine Cyclooxygenase 2 Cell culture Molecular Medicine Phosphorylation lipids (amino acids peptides and proteins) Inflammation Mediators Signal transduction Signal Transduction |
| Zdroj: | Journal of Natural Products. 81:356-363 |
| ISSN: | 1520-6025 0163-3864 |
| Popis: | An investigation of the jellyfish-derived fungus Penicillium chrysogenum J08NF-4 led to the isolation of two new meroterpene derivatives, chrysogenester (1) and 5-farnesyl-2-methyl-1-O-methylhydroquinone (2), and four known farnesyl meroterpenes. Docking analysis of 1 showed that it binds to PPAR-γ in the same manner as the natural PPAR-γ agonist amorfrutin B (7). Compound 1 activated PPAR-γ in murine Ac2F liver cells and increased nuclear PPAR-γ protein levels in murine RAW 264.7 macrophages. Because one of the main biological functions of PPAR-γ agonists is to suppress inflammatory response, an in vitro study was performed to explore the anti-inflammatory potency of 1 and the mechanism involved. In RAW 264.7 macrophages, 1 inhibited phosphorylation of the NF-κB p65 subunit and suppressed the expression of the pro-inflammatory mediators iNOS, NO, COX-2, TNF-α, IL-1β, and IL-6. We propose 1 suppresses inflammatory responses by activating PPAR-γ and subsequently downregulating the NF-κB signaling pathway, thus reducing the expressions of pro-inflammatory mediators. |
| Databáze: | OpenAIRE |
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