Syk/NF-kappa B-targeted anti-inflammatory activity of Melicope accedens (Blume) TG Hartley methanol extract
- Authors
- Kim, JK[Kim, Jin Kyeong]; Choi, E[Choi, Eunju]; Hong, YH[Hong, Yo Han]; Kim, H[Kim, Haeyeop]; Jang, YJ[Jang, Young-Jin]; Lee, JS[Lee, Jong Sub]; Choung, ES[Choung, Eui Su]; Woo, BY[Woo, Byoung Young]; Hong, YD[Hong, Yong Deog]; Lee, S[Lee, Sarah]; Lee, BH[Lee, Byoung-Hee]; Bach, TT[Bach, Tran The]; Kim, JH[Kim, Ji Hye]; Kim, JH[Kim, Jong-Hoon]; Cho, JY[Cho, Jae Youl]
- Issue Date
- May-2021
- Publisher
- ELSEVIER IRELAND LTD
- Keywords
- Melicope accedens (Blume) TG hartley; Flavonoids; Quercetin; Anti-Inflammation; NF-kappa B; Syk; Gastritis
- Citation
- JOURNAL OF ETHNOPHARMACOLOGY, v.271
- Indexed
- SCIE
SCOPUS
- Journal Title
- JOURNAL OF ETHNOPHARMACOLOGY
- Volume
- 271
- URI
- https://scholarworks.bwise.kr/skku/handle/2021.sw.skku/17390
- DOI
- 10.1016/j.jep.2021.113887
- ISSN
- 0378-8741
- Abstract
- Ethnopharmacological relevance: Melicope accedens (Blume) Thomas G. Hartley is a plant included in the family Rutaceae and genus Melicope. It is a native plant from Vietnam that has been used for ethnopharmacology. In Indonesia and Malaysia, the leaves of M. accedens are applied externally to decrease fever. Aim of the study: The molecular mechanisms of the anti-inflammatory properties of M. accedens are not yet understood. Therefore, we examined those mechanisms using a methanol extract of M. accedens (Ma-ME) and determined the target molecule in macrophages. Materials and methods: We evaluated the anti-inflammatory effects of Ma-ME in lipopolysaccharide (LPS)stimulated RAW264.7 cells and in an HCl/EtOH-triggered gastritis model in mice. To investigate the anti-inflammatory activity, we performed a nitric oxide (NO) production assay and ELISA assay for prostaglandin E2 (PGE 2 ). RT-PCR, luciferase gene reporter assays, western blotting analyses, and a cellular thermal shift assay (CETSA) were conducted to identify the mechanism and target molecule of Ma-ME. The phytochemical composition of Ma-ME was analyzed by HPLC and LC-MS/MS. Results: Ma-ME suppressed the production of NO and PGE(2) and the mRNA expression of proinflammatory genes (iNOS, IL-1 beta, and COX-2) in LPS-stimulated RAW264.7 cells without cytotoxicity. Ma-ME inhibited NF-kappa B activation by suppressing signaling molecules such as I kappa B alpha, Akt, Src, and Syk. Moreover, the CETSA assay revealed that Ma-ME binds to Syk, the most upstream molecule in the NF-kappa B signal pathway. Oral administration of Ma-ME not only alleviated inflammatory lesions, but also reduced the gene expression of IL-1 beta and p-Syk in mice with HCl/EtOH-induced gastritis. HPLC and LC-MS/MS analyses confirmed that Ma-ME contains various anti-inflammatory flavonoids, including quercetin, daidzein, and nevadensin. Conclusions: Ma-ME exhibited anti-inflammatory activities in vitro and in vivo by targeting Syk in the NF-kappa B signaling pathway. Therefore, we propose that Ma-ME could be used to treat inflammatory diseases such as gastritis.
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Collections - Biotechnology and Bioengineering > Integrative Biotechnology > 1. Journal Articles
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