JS-III-49, a hydroquinone derivative, exerts anti-inflammatory activity by targeting Akt and p38

• 영문명: JS-III-49, a hydroquinone derivative, exerts anti-inflammatory activity by targeting Akt and p38
• 발행기관: 대한생리학회-대한약리학회
• 저자명: Young-Su Yi Mi-Yeon Kim Jae Youl Cho
• 간행물 정보: 『The Korean Journal of Physiology & Pharmacology』제21권 제3호, 345~352쪽, 전체 8쪽
• 주제분류: 의약학 > 의학일반
• 파일형태: PDF
• 발행일자: 2017.01.01

영문 초록

Since previous studies have reported that hydroquinone (HQ) exerted immunosuppressive and anti-inflammatory activity, various HQ derivatives have been synthesized and their biological activities investigated. In this study, we explored the anti-inflammatory activity of JS-III-49, a novel HQ derivative, in macrophagemediated inflammatory responses. JS-III-49 suppressed the production of the inflammatory mediators nitric oxide (NO) and prostaglandin E₂ (PGE₂) and downregulated the mRNA expression of the inflammatory enzymes cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) as well as the expression of the pro-inflammatory cytokines interleukin-6 (IL-6) and IL-1β without cytotoxicity in LPS-stimulated RAW264.7 cells. JS-III-49 inhibited nuclear translocation of the NF-κB transcription factors p65 and p50 by directly targeting Akt, an upstream kinase of theNF-κB pathway, in LPS-stimulated RAW264.7 cells. However, JS-III-49 did not directly inhibit the kinase activities of Src and Syk, which are upstream kinases of Akt, in LPSstimulatedRAW264.7 cells. Moreover, JS-III-49 suppressed the nuclear translocation of c-Fos, one of the components of AP-1, by specifically targeting p38, an upstream mitogen-activated protein kinase (MAPK) in the AP-1 pathway in LPS-stimulated RAW264.7 cells. These results suggest that JS-III-49 plays an anti-inflammatory role in LPS-stimulated macrophages by targeting Akt and p38 in the NF-κB and AP-1 pathways, respectively.

키워드

Akt Anti-inflammatory activity HQ derivative JS-III-49 Macrophages p38