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7,8-Dihydroxyflavone attenuates the release of pro-inflammatory mediators and cytokines in lipopolysaccharide-stimulated BV2 microglial cells through the suppression of the NF-κB and MAPK signaling pathways.
Int J Mol Med 2014; 33(4):1027-34IJ

Abstract

7,8-Dihydroxyflavone (7,8-DHF), a member of the flavonoid family, has received considerable attention as a selective tyrosine kinase receptor B agonist. However, the pharmacological mechanisms responsible for its anti-inflammatory activities in microglial cells have yet to be elucidated. In this study, we evaluated the anti-inflammatory effects of this compound on the production of inflammatory mediators and cytokines in lipopolysaccharide (LPS)-stimulated murine BV2 microglial cells. At non-toxic concentrations, 7,8-DHF attenuated the production of nitric oxide (NO) and prostaglandin E2 (PGE2), by inhibiting inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) expression, respectively. Furthermore, the release and expression of inflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), were inhibited by 7,8-DHF. In addition, 7,8-DHF suppressed nuclear factor-κB (NF-κB) translocation and its transcriptional activity by blocking IκB (IκB)-α degradation; in addition, it exerted suppressive effects on the phosphorylation of mitogen-activated protein kinases (MAPKs). These results indicate that 7,8-DHF possesses therapeutic potential against neurodegenerative diseases that involve microglial activation.

Authors+Show Affiliations

Department of Pharmacy, Busan National University, Busan 609-735, Republic of Korea.Department of Molecular Biology, Dongeui University, Busan 614-714, Republic of Korea.Department of Food and Nutrition, Dongeui University, Busan 614-714, Republic of Korea.Department of Life Science and Biotechnology, Dongeui University, Busan 614-714, Republic of Korea.Laboratory of Immunobiology, Department of Marine Life Sciences, Jeju National University, Jeju 690-756, Republic of Korea.Research Center for Anti-Aging Technology Development and Department of Biochemistry, Busan National University College of Medicine, Yangsan 626-870, Republic of Korea.Department of Pharmacy, Busan National University, Busan 609-735, Republic of Korea.Department of Anti-Aging Research Center and Blue-Bio Industry RIC, Dongeui University, Busan 614-714, Republic of Korea.

Pub Type(s)

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

Language

eng

PubMed ID

24535427

Citation

Park, Hye Young, et al. "7,8-Dihydroxyflavone Attenuates the Release of Pro-inflammatory Mediators and Cytokines in Lipopolysaccharide-stimulated BV2 Microglial Cells Through the Suppression of the NF-κB and MAPK Signaling Pathways." International Journal of Molecular Medicine, vol. 33, no. 4, 2014, pp. 1027-34.
Park HY, Park C, Hwang HJ, et al. 7,8-Dihydroxyflavone attenuates the release of pro-inflammatory mediators and cytokines in lipopolysaccharide-stimulated BV2 microglial cells through the suppression of the NF-κB and MAPK signaling pathways. Int J Mol Med. 2014;33(4):1027-34.
Park, H. Y., Park, C., Hwang, H. J., Kim, B. W., Kim, G. Y., Kim, C. M., ... Choi, Y. H. (2014). 7,8-Dihydroxyflavone attenuates the release of pro-inflammatory mediators and cytokines in lipopolysaccharide-stimulated BV2 microglial cells through the suppression of the NF-κB and MAPK signaling pathways. International Journal of Molecular Medicine, 33(4), pp. 1027-34. doi:10.3892/ijmm.2014.1652.
Park HY, et al. 7,8-Dihydroxyflavone Attenuates the Release of Pro-inflammatory Mediators and Cytokines in Lipopolysaccharide-stimulated BV2 Microglial Cells Through the Suppression of the NF-κB and MAPK Signaling Pathways. Int J Mol Med. 2014;33(4):1027-34. PubMed PMID: 24535427.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 7,8-Dihydroxyflavone attenuates the release of pro-inflammatory mediators and cytokines in lipopolysaccharide-stimulated BV2 microglial cells through the suppression of the NF-κB and MAPK signaling pathways. AU - Park,Hye Young, AU - Park,Cheol, AU - Hwang,Hye Jin, AU - Kim,Byung Woo, AU - Kim,Gi-Young, AU - Kim,Cheol Min, AU - Kim,Nam Deuk, AU - Choi,Yung Hyun, Y1 - 2014/02/10/ PY - 2013/10/09/received PY - 2014/02/03/accepted PY - 2014/2/19/entrez PY - 2014/2/19/pubmed PY - 2014/10/22/medline SP - 1027 EP - 34 JF - International journal of molecular medicine JO - Int. J. Mol. Med. VL - 33 IS - 4 N2 - 7,8-Dihydroxyflavone (7,8-DHF), a member of the flavonoid family, has received considerable attention as a selective tyrosine kinase receptor B agonist. However, the pharmacological mechanisms responsible for its anti-inflammatory activities in microglial cells have yet to be elucidated. In this study, we evaluated the anti-inflammatory effects of this compound on the production of inflammatory mediators and cytokines in lipopolysaccharide (LPS)-stimulated murine BV2 microglial cells. At non-toxic concentrations, 7,8-DHF attenuated the production of nitric oxide (NO) and prostaglandin E2 (PGE2), by inhibiting inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) expression, respectively. Furthermore, the release and expression of inflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), were inhibited by 7,8-DHF. In addition, 7,8-DHF suppressed nuclear factor-κB (NF-κB) translocation and its transcriptional activity by blocking IκB (IκB)-α degradation; in addition, it exerted suppressive effects on the phosphorylation of mitogen-activated protein kinases (MAPKs). These results indicate that 7,8-DHF possesses therapeutic potential against neurodegenerative diseases that involve microglial activation. SN - 1791-244X UR - https://www.unboundmedicine.com/medline/citation/24535427/78_Dihydroxyflavone_attenuates_the_release_of_pro_inflammatory_mediators_and_cytokines_in_lipopolysaccharide_stimulated_BV2_microglial_cells_through_the_suppression_of_the_NF_κB_and_MAPK_signaling_pathways_ L2 - http://www.spandidos-publications.com/ijmm/33/4/1027 DB - PRIME DP - Unbound Medicine ER -