title: 6'-O-Caffeoyldihydrosyringin isolated from Aster glehni suppresses lipopolysaccharide-induced iNOS, COX-2, TNF-α, IL-1β and IL-6 expression via NF-κB and AP-1 inactivation in RAW 264.7 macrophages.
abstract: Previously, we found that ethyl acetate extract fraction of Aster glehni exhibited anti-hyperuricemic effects in animal models and also five new caffeoylglucoside derivatives were isolated from this fraction. In this work, we evaluated the anti-inflammatory effects of these caffeoylglucoside derivatives and found that 6'-O-caffeoyldihydrosyringin (2, CDS) most potently inhibited the LPS-induced production of nitric oxide (NO) and prostaglandin E2 (PGE2) in RAW 264.7 macrophages. In addition, CDS was found to concentration-dependently reduce the production of NO, PGE2, and the pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β) induced by LPS in macrophages. Consistent with these observations, CDS concentration-dependently inhibited LPS-induced inducible nitric oxide synthase (iNOS) and cyclooxidase-2 (COX-2) expression at the protein level and also iNOS, COX-2, TNF-α, and IL-6, IL-1β expression at the mRNA level. Furthermore, CDS suppressed the LPS-induced transcriptional activities of nuclear factor-κB (NF-κB) and activator protein-1 (AP-1) as well as the phosphorylation of p65 and c-Fos. Taken together, these results suggest that the anti-inflammatory effect of CDS is associated with the downregulation of iNOS, COX-2, TNF-α, IL-1β, and IL-6 expression via the negative regulation of NF-κB and AP-1 activation in LPS-induced RAW 264.7 macrophages.
authors: Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea; Department of Life and Nanopharmaceutical Science, College of Pharmacy, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea.
authors: Seunghwan
authors: S
authors: Seo
authors: Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea; Department of Life and Nanopharmaceutical Science, College of Pharmacy, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea.
authors: Kyoung-Goo
authors: KG
authors: Lee
authors: Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea.
authors: Ji-Sun
authors: JS
authors: Shin
authors: Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea.
authors: Eun Kyoung
authors: EK
authors: Chung
authors: Research Institute for Basic Sciences and Department of Chemistry, College of Sciences, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea.
authors: Jae Yeol
authors: JY
authors: Lee
authors: Molecular Recognition Research Center, Materials and Life Science Research Division, Korea Institute of Science and Technology, Seoul 02792, Republic of Korea. Electronic address: khj@kist.re.kr.
authors: Hyoung Ja
authors: HJ
authors: Kim
authors: Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea; Department of Life and Nanopharmaceutical Science, College of Pharmacy, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea. Electronic address: ktlee@khu.ac.kr.
authors: Kyung-Tae
authors: KT
authors: Lee
mesh_terms: D000818:Animals; D031173:Aster Plant / Q000737:chemistry*; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000633:toxicity*; D051379:Mice
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides
keywords: 6′-O-Caffeoyldihydrosyringin; Activator protein-1; Aster glehni; Inflammation; Nuclear factor-κB