Myrsine seguinii ethanolic extract and its active component quercetin inhibit macrophage activation and peritonitis induced by LPS by targeting to Syk/Src/IRAK-1 |
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Authors: | Woo Seok Yang Deok Jeong Young-Su Yi Byoung-Hee Lee Tae Woong Kim Khin Myo Htwe Young-Dong Kim Kee Dong Yoon Sungyoul Hong Woo-Shin Lee Jae Youl Cho |
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Institution: | 1. Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea;2. Division of Biological Resources Coordination, National Institute of Biological Resources, Incheon 404-708, Republic of Korea;3. Department of Biochemistry, Kangwon National University, Chuncheon 200-701, Republic of Korea;4. Popa Mountain Park, Forest Department, Kyaukpadaung Township, Mandalay Division, Myanmar;5. Department of Life Science, Hallym University, Chuncheon 200-702, Republic of Korea;6. College of Pharmacy, The Catholic University of Korea, Bucheon 420-743, Republic of Korea;g Department of Forest Sciences, Seoul National University, Seoul 151-921, Republic of Korea |
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Abstract: | Ethnopharmacological relevanceMyrsine seguinii H. LÉVEILLÉ (syn. Rapanea neriifolia) (Myrsinaceae) is a medicinal plants traditionally used in Myanmar to treat infectious and inflammatory diseases. Since none of reports have systematically demonstrated the anti-inflammatory activity of this plant, we aimed to mechanistically understand the regulatory roles of the plant in inflammatory responses using the ethanolic extract of Myrsine seguinii (Ms-EE).Materials and methodsActivated macrophages and peritonitis symptoms induced by lipopolysaccharide (LPS) were employed. HPLC analysis was used to identify active components. To characterize direct target enzymes, kinase assay was established.ResultsMs-EE inhibited the production of nitric oxide (NO) and prostaglandin (PG)E2 in RAW264.7 cells and peritoneal macrophages stimulated by LPS. This extract suppressed the mRNA expression of the inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 genes by down-regulating the activation of nuclear factor (NF)-κB and activator protein (AP-1). Interestingly, it was found that Ms-EE can directly suppress the enzyme activities of Syk, Src, and interleukin-1 receptor-associated kinase-1 (IRAK-1). Similarly, orally administered Ms-EE inhibited the phosphorylation of Src and Syk in peritoneal exudate-derived cells prepared from peritonitis. Finally, HPLC analysis clearly demonstrated that quercetin is a major active component with suppressing activity on the release of inflammatory mediators (NO and PGE2), and the enzyme activities of Src, Syk, and IRAK-1.ConclusionMs-EE containing quercetin negatively modulates macrophage-mediated in vitro inflammatory responses and LPS-induced peritonitis by blocking the Src/Syk/NF-κB and IRAK-1/AP-1 pathways, which contributes to its major ethnopharmacological use as an anti-inflammatory herbal medicine. |
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