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http://dx.doi.org/10.4062/biomolther.2014.121

Arctigenin Increases Hemeoxygenase-1 Gene Expression by Modulating PI3K/AKT Signaling Pathway in Rat Primary Astrocytes  

Jeong, Yeon-Hui (Department of Molecular Medicine, Tissue Injury Defense Research Center, Ewha Womans University Medical School)
Park, Jin-Sun (Department of Molecular Medicine, Tissue Injury Defense Research Center, Ewha Womans University Medical School)
Kim, Dong-Hyun (Life and Nanopharmaceutical Sciences, College of Pharmacy, Kyung Hee University)
Kim, Hee-Sun (Department of Molecular Medicine, Tissue Injury Defense Research Center, Ewha Womans University Medical School)
Publication Information
Biomolecules & Therapeutics / v.22, no.6, 2014 , pp. 497-502 More about this Journal
Abstract
In the present study, we found that the natural compound arctigenin inhibited hydrogen peroxide-induced reactive oxygen species (ROS) production in rat primary astrocytes. Since hemeoxygenase-1 (HO-1) plays a critical role as an antioxidant defense factor in the brain, we examined the effect of arctigenin on HO-1 expression in rat primary astrocytes. We found that arctigenin increased HO-1 mRNA and protein levels. Arctigenin also increases the nuclear translocation and DNA binding of Nrf2/c-Jun to the antioxidant response element (ARE) on HO-1 promoter. In addition, arctigenin increased ARE-mediated transcriptional activities in rat primary astrocytes. Further mechanistic studies revealed that arctigenin increased the phosphorylation of AKT, a downstream substrate of phosphatidylinositol 3-kinase (PI3K). Treatment of cells with a PI3K-specific inhibitor, LY294002, suppressed the HO-1 expression, Nrf2 DNA binding and ARE-mediated transcriptional activities in arctigenin-treated astrocyte cells. The results collectively suggest that PI3K/AKT signaling pathway is at least partly involved in HO-1 expression by arctigenin via modulation of Nrf2/ARE axis in rat primary astrocytes.
Keywords
Arctigenin; Astrocyte; Hemeoxygenase-1; PI3K/AKT; Nrf2/ARE axis;
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1 Chen, J. H., Huang, S. M., Tan, T. W., Lin, H. Y., Chen, P. Y., Yeh, W. L., Chou, S. C., Tsai, C. F., Wei, I. H. and Lu, D. Y. (2012) Berberine induces heme oxygenase-1 up-regulation through phosphatidylinositol 3-kinase/AKT and NF-E2-related factor-2 signaling pathway in astrocytes. Int. Immunopharmacol. 12, 94-100.   DOI   ScienceOn
2 Cho, M. K., Jang, Y. P., Kim, Y. C. and Kim, S. G. (2004) Arctigenin, a phenylpropanoid dibenzylbutyrolactone lignan, inhibits MAP kinases and AP-1 activation via potent MKK inhibition: the role in TNF-alpha inhibition. Int. Immunopharmacol. 4, 1419-1429.   DOI   ScienceOn
3 Dallerac, G., Chever, O. and Rouach, N. (2013) How do astrocytes shape synaptic transmission? Insights from electrophysiology. Front. Cell. Neurosci. 7, 159.
4 de Vries, H. E., Witte, M., Hondius, D., Rozemuller, A. J., Drukarch, B., Hoozemans, J. and van Horssen, J. (2008) Nrf2-induced antioxidant protection: a promising target to counteract ROS-mediated damage in neurodegenerative disease? Free Radic. Biol. Med. 45, 1375-1383.   DOI
5 Fan, T., Jiang, W. L., Zhu, J. and Feng Zhang, Y. (2012) Arctigenin protects focal cerebral ischemia-reperfusion rats through inhibiting neuroinflammation. Biol. Pharm. Bull. 35, 2004-2009.   DOI
6 Huang, S. L., Yu, R. T., Gong, J., Feng, Y., Dai, Y. L., Hu, F., Hu, Y. H., Tao, Y. D. and Leng, Y. (2012) Arctigenin, a natural compound, activates AMP-activated protein kinase via inhibition of mitochondria complex I and ameliorates metabolic disorders in ob/ob mice. Diabetologia 55, 1469-1481.   DOI
7 Hyam, S. R., Lee, I. A., Gu, W., Kim, K. A., Jeong, J. J., Jang, S. E., Han, M. J. and Kim, D. H. (2013) Arctigenin ameliorates inflammation in vitro and in vivo by inhibiting the PI3K/AKT pathway and polarizing M1 macrophages to M2-like macrophages. Eur. J. Pharmacol. 708, 21-29.   DOI
8 Jung, J. S., Shin, J. A., Park, E. M., Lee, J. E., Kang, Y. S., Min, S. W., Kim, D. H., Hyun, J. W., Shin, C. Y. and Kim, H. S. (2010) Anti-inflammatory mechanism of ginsenoside Rh1 in lipopolysaccharide-stimulated microglia: critical role of the protein kinase A pathway and hemeoxygenase-1 expression. J. Neurochem. 115, 1668-1680.   DOI   ScienceOn
9 Li, D., Liu, Q., Jia, D., Dou, D., Wang, X. and Kang, T. (2014) Protective effect of arctigenin against MPP+ and MPTP-induced neurotoxicity. Planta Med. 80, 48-55.   DOI
10 Kou, X., Qi, S., Dai, W., Luo, L. and Yin, Z. (2011) Arctigenin inhibits lipopolysaccharide-induced iNOS expression in RAW264.7 cells through suppressing JAK-STAT signal pathway. Int. Immunopharmacol. 11, 1095-1102.   DOI   ScienceOn
11 Lee, E. J. and Kim, H. S. (2011) Inhibitory mechanism of MMP-9 gene expression by ethyl pyruvate in lipopolysaccharide-stimulated BV2 microglial cells. Neurosci. Lett. 493, 38-43.   DOI
12 Lee, J. M., Li, J., Johnson, D. A., Stein, T. D., Kraft, A. D., Calkins, M. J., Jakel, R. J. and Johnson, J. A. (2005) Nrf2, a multi-organ protector? FASEB J. 19, 1061-1066.   DOI
13 Lee, J. S. and Surh, Y. J. (2005) Nrf2 as a novel molecular target for chemoprevention. Cancer Lett. 224, 171-184.   DOI   ScienceOn
14 Mates, J. M. (2000) Effects of antioxidant enzymes in the molecular control of reactive oxygen species toxicology. Toxicology 153, 83-104.   DOI   ScienceOn
15 Li, M. H., Cha Y. N. and Surh Y. J. (2006) Peroxynitrite induces HO-1 expression via PI3K/Akt-dependent activation of NF-E2-related factor 2 in PC12 cells. Free Radic. Biol. Med. 41, 1079-1091.   DOI   ScienceOn
16 Lim, J. H., Kim, K. M., Kim, S. W., Hwang, O. and Choi, H. J. (2008) Bromocriptine activates NQO1 via Nrf2-PI3K/Akt signaling: novel cytoprotective mechanism against oxidative damage. Pharmacol. Res. 57, 325-331.   DOI   ScienceOn
17 Martin, D., Rojo, A. I., Salinas, M., Diaz, R., Gallardo, G., Alam, J., De, Galarreta, C.M. and Cuadrado, A. (2004) Regulation of heme oxygenase-1 expression through the phosphatidylinositol 3-kinase/ Akt pathway and the Nrf2 transcription factor in response to the antioxidant phytochemical carnosol. J. Biol. Chem. 279, 8919-8929.   DOI   ScienceOn
18 Otterbein, L. E., Soares, M. P., Yamashita, K. and Bach, F. H. (2003) Heme oxygenase-1: unleashing the protective properties of heme. Trends Immunol. 24, 449-455.   DOI   ScienceOn
19 Park, J. H., Hong, Y. J., Moon E., Kim S. A., and Kim, S. Y. (2011a) Forsythiae fructus and its active component, arctigenin, provide neuroprotection by inhibiting neuroinflammation. Biomol. Ther. 19, 425-430.   DOI   ScienceOn
20 Park, J. S., Jung, J. S., Jeong, Y. H., Hyun, J. W., Le, T. K., Kim, D. H., Choi, E. C. and Kim, H. S. (2011b) Antioxidant mechanism of isoflavone metabolites in hydrogen peroxide-stimulated rat primary astrocytes: critical role of hemeoxygenase-1 and NQO1 expression. J. Neurochem. 119, 909-919.   DOI
21 Shi, X., Sun, H., Zhou, D., Xi, H. and Shan, L. (2014) Arctigenin attenuates lipopolysaccharide-induced acute lung injury in rats. Inflammation [Epub ahed of print]
22 Surh Y. J. (2003) Cancer chemoprevention with dietary phytochemicals. Nat. Rev. Cancer 3, 768-780.   DOI   ScienceOn
23 Park, J. S. and Kim, H. S. (2014) Regulation of hemeoxygenase-1 gene expression by Nrf2 and c-Jun in tertiary butylhydroquinonestimulated rat primary astrocytes. Biochem. Biophys. Res. Commun. 447, 672-677.   DOI
24 Park, J. S., Woo, M. S., Kim, D. H., Hyun, J. W., Kim, W. K., Lee, J. C. and Kim, H. S. (2007) Anti-inflammatory mechanisms of isoflavone metabolites in lipopolysaccharide-stimulated microglial cells. J. Pharmacol. Exp. Ther. 320, 1237-1245.   DOI
25 Ryter, S. W., Alam, J. and Choi, A. M. (2006) Heme oxygenase-1/carbon monoxide: from basic science to therapeutic applications. Physiol. Rev. 86, 583-650.   DOI   ScienceOn
26 Syapin, P. J. (2008) Regulation of haeme oxygenase-1 for treatment of neuroinflammation and brain disorders. Br. J. Pharmacol. 155, 623-640.
27 Vargas, M. R. and Johnson, J. A. (2009) The Nrf2-ARE cytoprotective pathway in astrocytes. Expert Rev. Mol. Med. 11, e17.   DOI   ScienceOn
28 Wang, H. Q., Xu, Y. X. and Zhu, C. Q. (2012) Upregulation of heme oxygenase-1 by acteoside through ERK and PI3 K/Akt pathway confer neuroprotection against beta-amyloid-induced neurotoxicity. Neurotox. Res. 21, 368-378.   DOI
29 Woo, M. S., Jang, P. G., Park, J. S., Kim, W. K., Joh, T. H. and Kim, H. S. (2003) Selective modulation of lipopolysaccharide-stimulated cytokine expression and mitogen-activated protein kinase pathways by dibutyryl-cAMP in BV2 microglial cells. Brain Res. Mol. Brain Res. 113, 86-96.   DOI   ScienceOn
30 Wu, R. M., Sun, Y. Y., Zhou, T. T., Zhu, Z. Y., Zhuang, J. J., Tang, X., Chen, J., Hu, L. H. and Shen, X. (2014) Arctigenin enhances swimming endurance of sedentary rats partially by regulation of antioxidant pathways. Acta Pharmacol. Sin. 35, 1274-1284.   DOI
31 Zhu, Z., Yan, J., Jiang, W., Yao, X. G., Chen, J., Chen, L., Li, C., Hu, L., Jiang, H. and Shen, X. (2013) Arctigenin effectively ameliorates memory impairment in Alzheimer's disease model mice targeting both beta-amyloid production and clearance. J. Neurosci. 33, 13138-13149.   DOI
32 Jang, Y. P., Kim, S. R., Choi, Y. H., Kim, J., Kim, S. G., Markelonis, G. J., Oh, T. H. and Kim, Y. C. (2002) Arctigenin protects cultured cortical neurons from glutamate-induced neurodegeneration by binding to kainate receptor. J. Neurosci. Res. 68, 233-240.   DOI   ScienceOn