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Euscaphic acid isolated from roots of Rosa rugosa inhibits LPS-induced inflammatory responses via TLR4-mediated NF-κB inactivation in RAW 264.7 macrophages.
J Cell Biochem 2012; 113(6):1936-46JC

Abstract

As an attempt to search for bioactive natural products exerting anti-inflammatory activity, we have evaluated the anti-inflammatory effects of euscaphic acid (19α-hydroxyursane-type triterpenoids, EA) isolated from roots of Rosa rugosa and its underlying molecular mechanisms in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. EA concentration-dependently reduced the production of nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) induced by LPS in RAW 264.7 macgophages. Consistent with these data, expression levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein and iNOS, COX-2, TNF-α, and IL-1β mRNA were inhibited by EA in a concentration-dependent manner. In addition, EA attenuated LPS-induced DNA binding and transcriptional activity of nuclear factor-kappa B (NF-κB), which was accompanied by a parallel reduction of degradation and phosphorylation of inhibitory kappa Bα (IκBα) and consequently by decreased nuclear translocation of p65 subunit of NF-κB. Pretreatment with EA significantly inhibited the LPS-induced phosphorylation of IκB kinase β (IKKβ), p38, and JNK, whereas the phosphorylation of ERK1/2 was unaffected. Furthermore, EA interfered with the LPS-induced clustering of TNF receptor-associated factor 6 (TRAF6) with interleukin receptor associated kinase 1 (IRAK1) and transforming growth factor-β-activated kinase 1 (TAK1). Taken together, these results suggest that EA inhibits LPS-induced inflammatory responses by interference with the clustering of TRAF6 with IRAK1 and TAK1, resulting in blocking the activation of IKK and MAPKs signal transduction to downregulate NF-κB activations.

Authors+Show Affiliations

Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, Seoul 130-701, Republic of Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22234926

Citation

Kim, In-Tae, et al. "Euscaphic Acid Isolated From Roots of Rosa Rugosa Inhibits LPS-induced Inflammatory Responses Via TLR4-mediated NF-κB Inactivation in RAW 264.7 Macrophages." Journal of Cellular Biochemistry, vol. 113, no. 6, 2012, pp. 1936-46.
Kim IT, Ryu S, Shin JS, et al. Euscaphic acid isolated from roots of Rosa rugosa inhibits LPS-induced inflammatory responses via TLR4-mediated NF-κB inactivation in RAW 264.7 macrophages. J Cell Biochem. 2012;113(6):1936-46.
Kim, I. T., Ryu, S., Shin, J. S., Choi, J. H., Park, H. J., & Lee, K. T. (2012). Euscaphic acid isolated from roots of Rosa rugosa inhibits LPS-induced inflammatory responses via TLR4-mediated NF-κB inactivation in RAW 264.7 macrophages. Journal of Cellular Biochemistry, 113(6), pp. 1936-46. doi:10.1002/jcb.24062.
Kim IT, et al. Euscaphic Acid Isolated From Roots of Rosa Rugosa Inhibits LPS-induced Inflammatory Responses Via TLR4-mediated NF-κB Inactivation in RAW 264.7 Macrophages. J Cell Biochem. 2012;113(6):1936-46. PubMed PMID: 22234926.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Euscaphic acid isolated from roots of Rosa rugosa inhibits LPS-induced inflammatory responses via TLR4-mediated NF-κB inactivation in RAW 264.7 macrophages. AU - Kim,In-Tae, AU - Ryu,Suran, AU - Shin,Ji-Sun, AU - Choi,Jung-Hye, AU - Park,Hee-Juhn, AU - Lee,Kyung-Tae, PY - 2012/1/12/entrez PY - 2012/1/12/pubmed PY - 2012/9/22/medline SP - 1936 EP - 46 JF - Journal of cellular biochemistry JO - J. Cell. Biochem. VL - 113 IS - 6 N2 - As an attempt to search for bioactive natural products exerting anti-inflammatory activity, we have evaluated the anti-inflammatory effects of euscaphic acid (19α-hydroxyursane-type triterpenoids, EA) isolated from roots of Rosa rugosa and its underlying molecular mechanisms in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. EA concentration-dependently reduced the production of nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) induced by LPS in RAW 264.7 macgophages. Consistent with these data, expression levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein and iNOS, COX-2, TNF-α, and IL-1β mRNA were inhibited by EA in a concentration-dependent manner. In addition, EA attenuated LPS-induced DNA binding and transcriptional activity of nuclear factor-kappa B (NF-κB), which was accompanied by a parallel reduction of degradation and phosphorylation of inhibitory kappa Bα (IκBα) and consequently by decreased nuclear translocation of p65 subunit of NF-κB. Pretreatment with EA significantly inhibited the LPS-induced phosphorylation of IκB kinase β (IKKβ), p38, and JNK, whereas the phosphorylation of ERK1/2 was unaffected. Furthermore, EA interfered with the LPS-induced clustering of TNF receptor-associated factor 6 (TRAF6) with interleukin receptor associated kinase 1 (IRAK1) and transforming growth factor-β-activated kinase 1 (TAK1). Taken together, these results suggest that EA inhibits LPS-induced inflammatory responses by interference with the clustering of TRAF6 with IRAK1 and TAK1, resulting in blocking the activation of IKK and MAPKs signal transduction to downregulate NF-κB activations. SN - 1097-4644 UR - https://www.unboundmedicine.com/medline/citation/22234926/Euscaphic_acid_isolated_from_roots_of_Rosa_rugosa_inhibits_LPS_induced_inflammatory_responses_via_TLR4_mediated_NF_κB_inactivation_in_RAW_264_7_macrophages_ L2 - https://doi.org/10.1002/jcb.24062 DB - PRIME DP - Unbound Medicine ER -