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DOI: 10.1055/s-0029-1185906
© Georg Thieme Verlag KG Stuttgart · New York
Protective Effect of Sauchinone by Upregulating Heme Oxygenase-1 via the P38 MAPK and Nrf2/ARE Pathways in HepG2 Cells
Publication History
received April 23, 2009
revised June 5, 2009
accepted June 11, 2009
Publication Date:
09 July 2009 (online)
![](https://www.thieme-connect.de/media/plantamedica/201001/lookinside/thumbnails/10.1055-s-0029-1185906-1.jpg)
Abstract
Sauchinone, a unique lignan isolated from the roots of Saururus chinensis (Lour.) Baill. (Saururaceae), is reported to exert potent hepatoprotective, anti-inflammatory actions and inhibitory effects on bone resorption. This study investigated the potency of sauchinone as a hepatic heme oxygenase (HO)-1 inducer and its protective effects in HepG2 cells. Treatment of the cells with sauchinone induced HO-1 expression and increased HO activity in a concentration- and time-dependent manner. This expression conferred cytoprotection against oxidative injury induced by t-butyl hydroperoxide. HO-1 expression by sauchinone also suppressed t-butyl hydroperoxide-induced reactive oxygen species generation in HepG2 cells. Moreover, sauchinone promoted the nuclear accumulation of the nuclear factor, E2-related factor 2 (Nrf2), and increased the promoter property of the antioxidant response element (ARE). Furthermore, treatment of the cells with a p38 MAPK inhibitor (SB203580) reduced sauchine-induced HO-1 expression and its protective effects. These results suggest that sauchinone increases the cellular resistance of HepG2 cells to t-butyl hydroperoxide-induced oxidative injury, presumably through the p38 MAPK pathway-Nrf2/ARE-dependent HO-1 expression.
Key words
sauchinone - Saururus chinensis (Lour.) Baill. - Saururaceae - heme oxygenase‐1 - t‐butyl hydroperoxide - HepG2 cells
References
- 1 Sung S H, Kim Y C. Hepatoprotective diastereomeric lignans from Saururus chinensis herbs. J Nat Prod. 2000; 63 1019-1021
- 2 Sung S H, Lee E J, Cho J H, Kim H S, Kim Y C. Sauchinone, a lignan from Saururus chinensis, attenuates CCl4-induced toxicity in primary cultures of rat hepatocytes. Biol Pharm Bull. 2000; 23 666-668
- 3 Lee A K, Sung S H, Kim Y C, Kim S G. Inhibition of lipopolysaccharide-inducible nitric oxide synthase, TNF-alpha and COX‐2 expression by sauchinone effects on I-kappaBalpha phosphorylation, C/EBP and AP‐1 activation. Br J Pharmacol. 2003; 139 11-20
- 4 Song H, Kim Y C, Moon A. Sauchinone, a lignan from Saururus chinensis, inhibits staurosporine-induced apoptosis in C6 rat glioma cells. Biol Pharm Bull. 2003; 26 1428-1430
- 5 Park S Y, Lee S H, Choi W H, Koh E M, Seo J H, Ryu S Y, Kim Y S, Kwon D Y, Koh W S. Immunosuppressive lignans isolated from Saururus chinensis. Planta Med. 2007; 73 674-678
- 6 Hwang B Y, Lee J H, Jung H S, Kim K S, Nam J B, Hong Y S, Paik S G, Lee J J. Sauchinone, a lignan from Saururus chinensis, suppresses iNOS expression through the inhibition of transactivation activity of RelA of NF-kappaB. Planta Med. 2003; 69 1096-1101
- 7 Han K Y, Yang D, Chang E J, Lee Y, Huang H, Sung S H, Lee Z H, Kim Y C, Kim H H. Inhibition of osteoclast differentiation and bone resorption by sauchinone. Biochem Pharmacol. 2007; 74 911-923
- 8 Loguercio C, Federico A. Oxidative stress in viral and alcoholic hepatitis. Free Radic Biol Med. 2003; 34 1-10
- 9 Dalle-Donne I, Rossi R, Colombo R, Ciustarini D, Milzani A. Biomakers of oxidative damage in human disease. Clin Chem. 2006; 52 601-623
- 10 Kaur I P, Geetha T. Screening methods for antioxidants. Mini Rev Med Chem. 2006; 6 305-312
- 11 Crimi E, Sica V, Williams-Ignarro S, Zhang H, Slutsky A S, Ignarro L J, Napoli C. The role of oxidative stress in adult critical care. Free Radic Biol Med. 2005; 40 398-406
- 12 Kapitulnik J. Bilirubin: an endogenous product of heme degradation with both cytotoxic and cytoprotective properties. Mol Pharmacol. 2004; 66 773-779
- 13 Kirkby K A, Adin C A. Products of heme oxygenase and their potential therapeutic applications. Am J Physiol Renal Physiol. 2006; 290 F563-F571
- 14 Morse D, Choi A M. Heme oxygenase-1: the “emerging molecule” has arrived. Am J Respir Cell Mol Biol. 2002; 27 8-16
- 15 Maines M D. The heme oxygenase system: a regulator of second messenger gases. Annu Rev Pharmacol Toxicol. 1997; 37 517-554
- 16 Jeong G S, Oh G S, Pae H O, Jeong S O, Kim Y C, Shin M K, Seo B Y, Han S Y, Lee H S, Jeong J G, Koh J S, Chung H T. Comparative effects of curcuminoids on endothelial heme oxygenase-1 expression: ortho-methoxy groups are essential to enhance heme oxygenase activity and protection. Exp Mol Med. 2006; 38 393-400
- 17 Jeong G S, Pae H O, Jeong S O, Kim Y C, Kwon T O, Lee H S, Kim N S, Park S D, Chung H T. The alpha-methylene-gamma-butyrolactone moiety in dehydrocostus lactone is responsible for cytoprotective heme oxygenase-1 expression through activation of the nuclear factor E2-related factor 2 in HepG2 cells. Eur J Pharmacol. 2007; 565 37-44
- 18 Jeong G S, An R B, Pae H O, Chung H T, Yoon K H, Kang D G, Lee H S, Kim Y C. Cudratricusxanthone A protects mouse hippocampal cells against glutamate-induced neurotoxicity via the induction of heme oxygenase-1. Planta Med. 2008; 74 1368-1373
- 19 Jeong G S, Li B, Lee D S, Kwon J W, Lee H S, Kwon T O, Kim Y C. Hepatoprotective constituents of Saururus chinensis roots against tacrine-induced cytotoxicity in human liver-derived HepG2 cells. Kor J Pharmcognosy. 2007; 38 176-180
- 20 Lemasters J J, Nieminen A L, Qian T, Trost L C, Elmore S P, Nishimura Y, Crowe R A, Cascio W E, Bradham C A, Brenner D A, Herman B. The mitochondrial permeability transition in cell death: a common mechanism in necrosis, apoptosis and autophagy. Biochim Biophys Acta. 1998; 1366 177-196
- 21 Alam J, Stewart D, Touchard C, Bionapally S, Choi A M, Cook J L. Nrf2, a Cap'n'Collar transcription factor, regulates induction of the heme oxygenase-1 gene. J Biol Chem. 1999; 274 26071-26078
- 22 Nguyen T, Sherratt P J, Pickett C B. Regulatory mechanisms controlling gene expression mediated by the antioxidant response element. Annu Rev Pharmacol Toxicol. 2003; 43 233-260
- 23 Kietzmann T, Samoylenko A, Immenschuh S. Transcriptional regulation of heme oxygenase-1 gene expression by MAP kinases of the JNK and p 38 pathways in primary cultures of rat hepatocytes. J Biol Chem. 2003; 278 17927-17936
- 24 Choi B M, Kim Y M, Jeong Y R, Pae H O, Song C E, Park J E, Ahn Y K, Chung H T. Induction of heme oxygenase-1 is involved in anti-proliferative effects of paclitaxel on rat vascular smooth muscle cells. Biochem Biophys Res Commun. 2004; 321 132-137
- 25 Balogun E, Hoque M, Gong P, Killeen E, Green C J, Foresti R, Alam J, Motterlini R. Curcumin activates the haem oxygenase-1 gene via regulation of Nrf2 and the antioxidant-responsive element. Biochem J. 2003; 371 887-895
- 26 Das S, Fraga C G, Das D K. Cardioprotective effect of resveratrol via HO‐1 expression involves p 38 map kinase and PI‐3-kinase signaling, but does not involve NF-kappaB. Free Radic Res. 2006; 40 1066-1075
- 27 Haridas V, Hanausek M, Nishimura G, Soehnge H, Gaikwad A, Narog M, Spears E, Zoltaszek R, Walaszek Z, Gutterman J U. Triterpenoid electrophiles (avicins) activate the innate stress response by redox regulation of a gene battery. J Clin Invest. 2004; 113 65-73
- 28 Itoh K, Chiba T, Takahashi S, Ishii T, Igarashi K, Katoh Y, Oyake T, Hayashi N, Satoh K, Hatayama I, Yamamoto M, Nabeshiman Y. An Nrf2/small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements. Biochem Biophys Res Commun. 1997; 236 313-322
Prof. Youn-Chul Kim
Zoonosis Research Center
Wonkwang University
Iksan
Jeonbuk 570–749
Republic of Korea
Phone: + 82 6 38 50 68 23
Fax: + 82 6 38 52 88 37
Email: yckim@wku.ac.kr