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Isobutyrylshikonin inhibits lipopolysaccharide-induced nitric oxide and prostaglandin E2 production in BV2 microglial cells by suppressing the PI3K/Akt-mediated nuclear transcription factor-κB pathway.
Nutr Res 2014; 34(12):1111-9NR

Abstract

Microglia are important macrophages to defend against pathogens in the central nervous system (CNS); however, persistent or acute inflammation of microglia lead to CNS disorders via neuronal cell death. Therefore, we theorized that a good strategy for the treatment of CNS disorders would be to target inflammatory mediators from microglia in disease. Consequently, we investigated whether isobutyrylshikonin (IBS) attenuates the production of proinflammatory mediators, such as nitric oxide (NO) and prostaglandin E2, in lipopolysaccharide (LPS)-stimulated BV2 microglial cells. Treatment with IBS inhibited the secretion of NO and prostaglandin E2 (as well as the expression of their key regulatory genes), inducible NO synthase (iNOS), and cyclooxygenase-2 (COX-2). Isobutyrylshikonin also suppressed LPS-induced DNA-binding activity of nuclear transcription factor-κB (NF-κB), by inhibiting the nuclear translocation of p50 and p65 in addition to blocking the phosphorylation and degradation of IκBα. Pretreatment with pyrrolidine dithiocarbamate, a specific NF-κB inhibitor, showed the down-regulation of LPS-induced iNOS and COX-2 messenger RNA by suppressing NF-κB activity. This indirectly suggests that IBS-mediated NF-κB inhibition is the main signaling pathway involved in the inhibition of iNOS and COX-2 expression. In addition, IBS attenuated LPS-induced phosphorylation of PI3K and Akt, which are upstream molecules of NF-κB, in LPS-stimulated BV2 microglial cells. The functional aspects of the PI3K/Akt signaling pathway were analyzed with LY294002, which is a specific PI3K/Akt inhibitor that attenuated LPS-induced iNOS and COX-2 expression by suppressing NF-κB activity. These data suggest that an IBS-mediated anti-inflammatory effect may be involved in suppressing the PI3K/Akt-mediated NF-κB signaling pathway.

Authors+Show Affiliations

Department of Marine Life Sciences, Jeju National University, Jeju 690-756, Republic of Korea.Division of Wood Chemistry & Microbiology, Department of Forest Products, Korea forest Research Institute, 57 Hoegiro, Dongdaemun-gu, Seoul 130-712, Republic of Korea.Department of Marine Life Sciences, Jeju National University, Jeju 690-756, Republic of Korea.Department of Marine Life Sciences, Jeju National University, Jeju 690-756, Republic of Korea.Division of Wood Chemistry & Microbiology, Department of Forest Products, Korea forest Research Institute, 57 Hoegiro, Dongdaemun-gu, Seoul 130-712, Republic of Korea.Department of Biochemistry, College of Oriental Medicine, Dong-Eui University, Busan 614-050, Republic of Korea.Department of Microbiology, College of Medicine, Inje University, Busan 614-735 Republic of Korea. Electronic address: cihima@inje.ac.kr.Department of Marine Life Sciences, Jeju National University, Jeju 690-756, Republic of Korea. Electronic address: immunkim@jejunu.ac.kr.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

25454762

Citation

Jayasooriya, Rajapaksha Gedara Prasad Tharanga, et al. "Isobutyrylshikonin Inhibits Lipopolysaccharide-induced Nitric Oxide and Prostaglandin E2 Production in BV2 Microglial Cells By Suppressing the PI3K/Akt-mediated Nuclear Transcription factor-κB Pathway." Nutrition Research (New York, N.Y.), vol. 34, no. 12, 2014, pp. 1111-9.
Jayasooriya RG, Lee KT, Kang CH, et al. Isobutyrylshikonin inhibits lipopolysaccharide-induced nitric oxide and prostaglandin E2 production in BV2 microglial cells by suppressing the PI3K/Akt-mediated nuclear transcription factor-κB pathway. Nutr Res. 2014;34(12):1111-9.
Jayasooriya, R. G., Lee, K. T., Kang, C. H., Dilshara, M. G., Lee, H. J., Choi, Y. H., ... Kim, G. Y. (2014). Isobutyrylshikonin inhibits lipopolysaccharide-induced nitric oxide and prostaglandin E2 production in BV2 microglial cells by suppressing the PI3K/Akt-mediated nuclear transcription factor-κB pathway. Nutrition Research (New York, N.Y.), 34(12), pp. 1111-9. doi:10.1016/j.nutres.2014.10.002.
Jayasooriya RG, et al. Isobutyrylshikonin Inhibits Lipopolysaccharide-induced Nitric Oxide and Prostaglandin E2 Production in BV2 Microglial Cells By Suppressing the PI3K/Akt-mediated Nuclear Transcription factor-κB Pathway. Nutr Res. 2014;34(12):1111-9. PubMed PMID: 25454762.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Isobutyrylshikonin inhibits lipopolysaccharide-induced nitric oxide and prostaglandin E2 production in BV2 microglial cells by suppressing the PI3K/Akt-mediated nuclear transcription factor-κB pathway. AU - Jayasooriya,Rajapaksha Gedara Prasad Tharanga, AU - Lee,Kyoung-Tae, AU - Kang,Chang-Hee, AU - Dilshara,Matharage Gayani, AU - Lee,Hak-Ju, AU - Choi,Yung Hyun, AU - Choi,Il-Whan, AU - Kim,Gi-Young, Y1 - 2014/10/07/ PY - 2013/11/26/received PY - 2014/09/29/revised PY - 2014/10/02/accepted PY - 2014/12/3/entrez PY - 2014/12/3/pubmed PY - 2015/7/29/medline KW - Isobutyrylshikonin KW - Nitric oxide KW - Nuclear factor-κB KW - PI3K/Akt KW - Prostaglandin E(2) SP - 1111 EP - 9 JF - Nutrition research (New York, N.Y.) JO - Nutr Res VL - 34 IS - 12 N2 - Microglia are important macrophages to defend against pathogens in the central nervous system (CNS); however, persistent or acute inflammation of microglia lead to CNS disorders via neuronal cell death. Therefore, we theorized that a good strategy for the treatment of CNS disorders would be to target inflammatory mediators from microglia in disease. Consequently, we investigated whether isobutyrylshikonin (IBS) attenuates the production of proinflammatory mediators, such as nitric oxide (NO) and prostaglandin E2, in lipopolysaccharide (LPS)-stimulated BV2 microglial cells. Treatment with IBS inhibited the secretion of NO and prostaglandin E2 (as well as the expression of their key regulatory genes), inducible NO synthase (iNOS), and cyclooxygenase-2 (COX-2). Isobutyrylshikonin also suppressed LPS-induced DNA-binding activity of nuclear transcription factor-κB (NF-κB), by inhibiting the nuclear translocation of p50 and p65 in addition to blocking the phosphorylation and degradation of IκBα. Pretreatment with pyrrolidine dithiocarbamate, a specific NF-κB inhibitor, showed the down-regulation of LPS-induced iNOS and COX-2 messenger RNA by suppressing NF-κB activity. This indirectly suggests that IBS-mediated NF-κB inhibition is the main signaling pathway involved in the inhibition of iNOS and COX-2 expression. In addition, IBS attenuated LPS-induced phosphorylation of PI3K and Akt, which are upstream molecules of NF-κB, in LPS-stimulated BV2 microglial cells. The functional aspects of the PI3K/Akt signaling pathway were analyzed with LY294002, which is a specific PI3K/Akt inhibitor that attenuated LPS-induced iNOS and COX-2 expression by suppressing NF-κB activity. These data suggest that an IBS-mediated anti-inflammatory effect may be involved in suppressing the PI3K/Akt-mediated NF-κB signaling pathway. SN - 1879-0739 UR - https://www.unboundmedicine.com/medline/citation/25454762/Isobutyrylshikonin_inhibits_lipopolysaccharide_induced_nitric_oxide_and_prostaglandin_E2_production_in_BV2_microglial_cells_by_suppressing_the_PI3K/Akt_mediated_nuclear_transcription_factor_κB_pathway_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0271-5317(14)00199-7 DB - PRIME DP - Unbound Medicine ER -