2. Academic Validation
  3. 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

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

  • Bioorg Med Chem Lett. 2016 Oct 1;26(19):4592-4598. doi: 10.1016/j.bmcl.2016.08.074.
Seunghwan Seo 1,  Kyoung-Goo Lee 1,  Ji-Sun Shin 2,  Eun Kyoung Chung 2,  Jae Yeol Lee 3,  Hyoung Ja Kim 4,  Kyung-Tae Lee 5
Affiliations

Affiliations

  • 1 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.
  • 2 Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea.
  • 3 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.
  • 4 Molecular Recognition Research Center, Materials and Life Science Research Division, Korea Institute of Science and Technology, Seoul 02792, Republic of Korea. Electronic address: [email protected].
  • 5 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: [email protected].
PMID: 27590705 DOI: 10.1016/j.bmcl.2016.08.074
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.

Keywords

6′-O-Caffeoyldihydrosyringin; Activator protein-1; Aster glehni; Inflammation; Nuclear factor-κB.

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