Browse > Article
http://dx.doi.org/10.5352/JLS.2017.27.1.8

Gardenia jasminoides Exerts Anti-inflammatory Activity via Akt and p38-dependent Heme Oxygenase-1 Upregulation in Microglial Cells  

Song, Ji Su (Department of Molecular Biology, College of Natural Sciences, Pusan National University)
Shin, Ji Eun (Department of Molecular Biology, College of Natural Sciences, Pusan National University)
Kim, Ji-Hee (Department of Molecular Biology, College of Natural Sciences, Pusan National University)
Kim, YoungHee (Department of Molecular Biology, College of Natural Sciences, Pusan National University)
Publication Information
Journal of Life Science / v.27, no.1, 2017 , pp. 8-14 More about this Journal
Abstract
Died Gardenia jasminoides fruit is used as a dye in the food and clothes industries in Asia. The present study investigated the anti-inflammatory effects of aqueous extract of G. jasminoides fruits (GJ) in BV-2 microglial cells. GJ inhibited lipopolysaccharide-induced nitric oxide (NO) secretion, inducible nitric oxide synthase (iNOS) expression, and reactive oxygen species production, without affecting cell viability. Furthermore, GJ increased the expression of heme oxygenase-1 (HO-1) in a dose-dependent manner. Moreover, the inhibitory effect of GJ on iNOS expression was abrogated by small interfering RNA-mediated knock-down of HO-1. In addition, GJ induced nuclear translocation of nuclear factor E2-related factor 2 (Nrf2), a transcription factor that regulates HO-1 expression. GJ-mediated expression of HO-1 was suppressed by LY294002, a phosphoinositide 3-kinase (PI-3K) inhibitor, and SB203580, a p38 kinase inhibitor, but not by the extracellular signal-regulated kinase (ERK) inhibitor PD98059 or c-Jun N-terminal kinase (JNK) inhibitor SP600125. GJ also enhanced the phosphorylation of Akt and p38. These results suggest that GJ suppresses the production of NO, a pro-inflammatory mediator, by inducing HO-1 expression via PI-3K/Akt/p38 signaling. These findings illustrate a novel molecular mechanism by which extract from G. jasminoides fruits inhibits neuroinflammation.
Keywords
Gardenia jasminoides; heme oxygenase-1; microglia; nitric oxide;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Lull, M. E. and Block, M. L. 2010. Microglial activation and chronic neurodegeneration. Neurotherapeutics 7, 354-365.   DOI
2 Otterbein, L. E., Bach, F. H., Alam, J., Soares, M., Tao Lu, H., Wysk, M., Davis, R. J., Flavell, R. A. and Choi, A. M. 2000. Carbon monoxide has anti-inflammatory effects involving the mitogen-activated protein kinase pathway. Nat. Med. 6, 422-428.   DOI
3 Ozaki, A., Kitano, M., Furusawa, N., Yamaguchi, H., Kuroda, K. and Endo, G. 2002. Genotoxicity of gardenia yellow and its components. Food Chem. Toxicol. 40, 1603-1610.   DOI
4 Paine, A., Eiz-Vesper, B., Blasczyk, R. and Immenschuh, S. 2010. Signaling to heme oxygenase-1 and its anti-inflammatory therapeutic potential. Biochem. Pharmacol. 80, 1895-1903.   DOI
5 Pamplona, A., Ferreira, A., Balla, J., Jeney, V., Balla, G., Epiphanio, S., Chora, A., Rodrigues, C. D., Gregoire, I. P., Cunha-Rodrigues, M., Portugal, S., Soares, M. P. and Mota, M. M. 2007. Heme oxygenase-1 and carbon monoxide suppress the pathogenesis of experimental cerebral malaria. Nat. Med. 13, 703-710.   DOI
6 Motohashi, H., Katsuoka, F., Engel, J. D. and Yamamoto, M. 2004. Small Maf proteins serve as transcriptional cofactors for keratinocyte differentiation in the Keap1-Nrf2 regulatory pathway. Proc. Natl. Acad. Sci. USA 101, 6379-6384.   DOI
7 Schallner, N., Fuchs, M., Schwer, C. I., Loop, T., Buerkle, H., Lagreze, W. A., van Oterendorp, C., Biermann, J. and Goebel, U. 2012. Postconditioning with inhaled carbon monoxide counteracts apoptosis and neuroinflammation in the ischemic rat retina. PLoS One 7, e46479.   DOI
8 Park, E. H., Joo, M. H., Kim, S. H. and Lim, C. J. 2003. Antiangiogenic activity of Gardenia jasminoides fruit. Phytother. Res. 17, 961-962.   DOI
9 Peng, K., Yang, L., Zhao, S., Chen, L., Zhao, F. and Qiu, F. 2013. Chemical constituents from the fruit of Gardenia jasminoides and their inhibitory effects on nitric oxide production. Bioorg. Med. Chem. Lett. 23, 1127-1131.   DOI
10 Ryter, S. W. and Choi, A. M. 2010. Heme oxygenase-1/ carbon monoxide: Novel therapeutic strategies in critical care medicine. Curr. Drug Targets 11, 1485-1494.   DOI
11 Srisook, K., Kim, C. and Cha, Y. N. 2005. Molecular mechanisms involved in enhancing HO-1 expression: De-repression by heme and activation by Nrf2, the "one-two" punch. Antioxid. Redox Signal. 7, 1674-1687.   DOI
12 Van Eldik, L. J., Thompson, W. L., Ralay Ranaivo, H., Behanna, H. A. and Martin Watterson, D. 2007. Glia proinflammatory cytokine upregulation as a therapeutic target for neurodegenerative diseases: Function-based and targetbased discovery approaches. Intl. Rev. Neurobiol. 82, 277-296.
13 Ahn, D. K. 2003. Illustrated book of Korean medicinal herbs, pp. 122, Kyohak Publishing Co.
14 Zhang, H., Xue, W., Wu, R., Gong, T., Tao, W., Zhou, X., Jiang, J., Zhang, Y., Zhang, N., Cui, Y., Chen, C. and Chen, G. 2015. Rapid antidepressant activity of ethanol extract of Gardenia jasminoides Ellis is associated with upregulation of bdnf expression in the hippocampus. Evid. Based Complement. Alternat. Med. 2015, 761238.
15 Boje, K. M. and Arora, P. K. 1992. Microglial-produced nitric oxide and reactive nitrogen oxides mediate neuronal cell death. Brain Res. 587, 250-256.   DOI
16 Chen, S., Zhao, X., Sun, P., Qian, J., Shi, Y. and Wang, R. 2016. Preventive effect of Gardenia jasminoides on HCl/ethanol induced gastric injury in mice. J. Pharmacol. Sci. 10.1016/j.jphs.2016.05.011.   DOI
17 Ballot, E., Bandin, O., Chazouilleres, O., Johanet, C. and Poupon, R. 2004. Immune response to lipopolysaccharide in primary biliary cirrhosis and autoimmune diseases. J. Autoimmun. 22, 153-158.   DOI
18 Chora, A. A., Fontoura, P., Cunha, A., Pais, T. F., Cardoso, S., Ho, P. P., Lee, L. Y., Sobel, R. A., Steinman, L. and Soares, M. P. 2007. Heme oxygenase-1 and carbon monoxide suppress autoimmune neuroinflammation. J. Clin. Invest. 117, 438-447.   DOI
19 Chen, Y. H., Lan, T., Li, J., Qiu, C. H., Wu, T., Gou, H. J. and Lu, M. Q. 2012. Gardenia jasminoides attenuates hepatocellular injury and fibrosis in bile duct-ligated rats and human hepatic stellate cells. World J. Gastroenterol. 18, 7158-7165.   DOI
20 Cheng, S. E., Lee, I. T., Lin, C. C., Kou, Y. R. and Yang, C. M. 2010. Cigarette smoke particle-phase extract induces HO-1 expression in human tracheal smooth muscle cells: Role of the c-Src/NADPH oxidase/MAPK/Nrf2 signaling pathway. Free Radic. Biol. Med. 48, 1410-1422.   DOI
21 Doherty, G. H. 2011. Nitric oxide in neurodegeneration: Potential benefits of non-steroidal anti-inflammatories. Neurosci. Bull. 27, 366-382.   DOI
22 Hong, Y. J. and Yang, K. S. 2013. Anti-inflammatory activities of crocetin derivatives from processed Gardenia jasminoides. Arch. Pharm. Res. 36, 933-940.   DOI
23 Innamorato, N. G., Lastres-Becker, I. and Cuadrado, A. 2009. Role of microglial redox balance in modulation of neuroinflammation. Curr. Opin. Neurol. 22, 308-314.   DOI
24 Jazwa, A. and Cuadrado, A. 2010. Targeting heme oxygenase-1 for neuroprotection and neuroinflammation in neurodegenerative diseases. Curr. Drug Targets. 11, 1517-1531.   DOI
25 Lawson, L. J., Perry, V. H. and Gordon, S. 1992. Turnover of resident microglia in the normal adult mouse brain. Neuroscience 48, 405-415.   DOI
26 Lin, W. H., Kuo, H. H., Ho, L. H., Tseng, M. L., Siao, A. C., Hung, C. T., Jeng, K. C. and Hou, C. W. 2015. Gardenia jasminoides extracts and gallic acid inhibit lipopolysaccharideinduced inflammation by suppression of JNK2/1 signaling pathways in BV-2 cells. Iran. J. Basic Med. Sci. 18, 555-562.