Three Polymethoxyflavones Purified from Ougan (Citrus reticulata Cv. Suavissima) Inhibited LPS-Induced NO Elevation in the Neuroglia BV-2 Cell Line via the JAK2/STAT3 Pathway
| Autor: | Yue Wang, Jinping Cao, Chongde Sun, Wenjing Zang, Shiyu Ji |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Lipopolysaccharides
0301 basic medicine JAK2/STAT3 pathway Citrus Lipopolysaccharide purification Cell Survival lcsh:TX341-641 Citrus reticulata cv. Suavissima Nitric Oxide High-performance liquid chromatography Article Nobiletin Cell Line NO release Mice 03 medical and health sciences chemistry.chemical_compound Tangeretin 0302 clinical medicine Downregulation and upregulation tangeretin polymethoxyflavone Animals nobiletin Nutrition and Dietetics Molecular Structure Flavones Molecular biology 5-demethylnobiletin neuroglia IκBα 030104 developmental biology chemistry Cell culture 030220 oncology & carcinogenesis TLR4 Microglia lcsh:Nutrition. Foods and food supply Food Science |
| Zdroj: | Nutrients, Vol 11, Iss 4, p 791 (2019) Nutrients Volume 11 Issue 4 |
| ISSN: | 2072-6643 |
| Popis: | In order to establish an efficient method for separation of polymethoxyflavones (PMFs) and explore the anti-inflammatory mechanism of PMF monomers, a citrus variety rich in PMFs, Ougan (Citrus reticulata cv. Suavissima), was selected, and three monomers, including nobiletin, tangeretin, and 5-demethylnobiletin, were purified by ultrasonic-assisted extraction, solid phase extraction, and high-speed countercurrent chromatography separation. UPLC-MS was used to identify the three monomers. UPLC determined purities of 99.87% to nobiletin, 99.76% to tangeretin, and 98.75% to 5-demethylnobiletin with the standard curve method. A lipopolysaccharide (LPS)-induced NO releasing model was performed in the mouse microglia BV-2 cell line. Results illustrated that PMF monomers inhibited the NO release and the inflammation-related cytokines, including IL-1&beta IL-6, and TNF&alpha elevation. QRT-PCR revealed that PMFs alleviated LPS-induced upregulation of iNOS, IL-6, JAK2, TNF&alpha IL-1&beta and NF-&kappa B and LPS-induced downregulation of I&kappa B&alpha while they did not affect TLR1, TLR2, TLR4, and TLR6. STAT3 expression was repressed by tangeretin and 5-demethylnobiletin, but not by nobiletin. Western blot assay also showed a suppression of expression and phosphorylation of JAK2 by all three PMF monomers, while STAT3 phosphorylation was restrained by tangeretin and 5-demethylnobiletin. The mechanism was primarily verified by the JAK2 inhibitor Ruxolitinib and the STAT3 inhibitor Stattic. |
| Databáze: | OpenAIRE |
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