题名

Induction of Nrf2-dependent Antioxidation and Protection Against Carbon Tetrachloride-induced Liver Damage by Andrographis Herba (穿心蓮 Chuān xīn lián) Ethanolic Extract

作者

Haw-Wen Chen;Yu-Ju Huang;Hsien-Tsung Yao;Chong-Kuei Lii

关键词

Andrographis paniculata ; Antioxidation ; Nrf2 ; Carbon tetrachloride

期刊名称

Journal of Traditional and Complementary Medicine

卷期/出版年月

2卷3期(2012 / 07 / 01)

页次

211 - 219

内容语文

英文

中文摘要

Andrographis paniculata is a traditional Chinese herb and displays diverse biological activities including antioxidation, anti-tumorigenesis, anti-virus, and anti-atherogenesis. In this study, we investigated the up-regulation of ethanolic extract of A. paniculata (APE) on the antioxidant defense in rat livers and whether this enhancement protected against carbon tetrachloride (CCl_4)-induced liver damage. Male Sprague-Dawley rats were orally administered (i.g.) 0, 0.75, or 2 g/kg/d APE for 5 d. At d 6, rats were sacrificed and liver tissues were removed. Some animals (n=8) were intraperitoneally injected CCl_4 (1 mL/kg, 50% in olive oil) and blood was drawn 24 h after CCl_4 treatment. The results showed that APE increased hepatic glutathione (GSH) content and superoxide dismutase, GSH peroxidase, and GSH S-transferase activities in a dose-dependent manner (p < 0.05). Results of immunoblotting and RT-PCR revealed that rats treated with APE had higher glutamate cysteine ligase catalytic and modifier subunits, heme oxygenase 1, superoxide dismutase 1, and GSH S-transferase Ya and Yb protein and mRNA expression than those of control rats. Moreover, APE increased Nrf2 nuclear translocation and Nrf2 binding to DNA in rat liver. In the presence of CCl_4, APE decreased hepatic thiobarbituric acid-reactive substances production and plasma aspartate aminotransferase and alanine aminotransferase activities. These results suggest that APE protection against CCl_4 insult is attributed, at least in part, to its up-regulation of antioxidant defense in rat liver.

主题分类 醫藥衛生 > 中醫藥學
参考文献
  1. Abraham, N.G.,Kappas, A.(2005).Heme oxygenase and the cardiovascular-renal system.Free Radic Biol Med,39,1-25.
  2. Aebi, H.(1984).Catalase in vitro.Methods Enzymol,105,121-126.
  3. Akowuah, G.A.,Zhari, I.,Mariam, A.,Yam, M.F.(2009).Absorption of andrographolides from Andrographis paniculata and its effect on CCl(4)-induced oxidative stress in rats.Food Chem Toxicol,47,2321-2326.
  4. Bellomo, G.,Mirabelli, F.,DiMonte, D.,Richelmi, P.,Thor, H.,Orrenius, C.,Orrenius, S.(1987).Formation and reduction of glutathione-protein mixed disulfides during oxidative stress.Biochem Pharmacol,36,1313-1320.
  5. Burgos, R.A.,Caballero, E.E.,Sánchez, N.S.,Schroeder, R.A.,Wikman, G.K.,Hancke, J.L.(1997).Testicular toxicity assessment of Andrographis paniculata dried extract in rats.J Ethnopharmacol,58,219-224.
  6. Cerný, D.,Canová, N.K.,Martínek, J.,Horínek, A.,Kmonícková, E.,Zídek, Z.,Farghali, H.(2009).Effects of resveratrol pretreatment on tert-butylhydroperoxide induced hepatocyte toxicity in immobilized perifused hepatocytes: involvement of inducible nitric oxide synthase and hemoxygenase-1.Nitric Oxide,20,1-8.
  7. Chao, C.Y.,Lii, C.K.,Tsai, I.T.,Li, C.C.,Liu, K.L.,Tsai, C.W.,Chen, H.W.(2011).Andrographolide inhibits ICAM-1 expression and NF-κB activation in TNF-α-treated EA.hy926 Cells.J Agric Food Chem,59,5263-5271.
  8. Chao, W.W.,Lin, B.F.(2010).Isolation and identification of bioactive compounds in Andrographis paniculata (Chuanxinlian).Chin Med,5,17.
  9. Chen, H.W.,Lin, A.H.,Chu, H.C.,Li, C.C.,Tsai, C.W.,Chao, C.Y.,Wang, C.J.,Lii, C.K.,Liu, K.L.(2011).Inhibition of TNF-α-induced inflammation by andrographolide via down-regulation of the PI3K/Akt signaling pathway.J Nat Prod,74,2408-2413.
  10. Clark, J.E.,Foresti, R.,Green, C.J.,Motterlini, R.(2000).Dynamics of haem oxygenase-1 expression and bilirubin production in cellular protection against oxidative stress.Biochem J,348,615-619.
  11. Cooke, M.S.,Evans, M.D.,Dizdaroglu, M.,Lunec, J.(2003).Oxidative DNA damage: mechanisms, mutation, and disease.FASEB J,17,1195-1214.
  12. Farghali, H.,Cerný, D.,Kameníková, L.,Martínek, J.,Horínek, A.,Kmonícková, E.,Zídek, Z.(2009).Resveratrol attenuates lipopolysaccharide-induced hepatitis in D-galactosamine sensitized rats: role of nitric oxide synthase 2 and heme oxygenase-1.Nitric Oxide,21,216-225.
  13. Fraga, C.G.,Leibovitz, B.E.,Tappel, A.L.(1988).Lipid peroxidation measured as thiobarbituric acid-reactive substance in tissue slices: characterization and comparison between homogenates and microsomes.Free Radic Biol Med,4,155-161.
  14. Franco, R.,Schoneveld, O.J.,Pappa, A.,Panayiotidis, M.I.(2007).The central role of glutathione in the pathophysiology of human diseases.Arch Physiol Biochem,113,234-258.
  15. Franklin, C.C.,Backos, D.S.,Mohar, I.,White, C.C.,Forman, H.J.,Kavanagh, T.J.(2009).Structure, function, and post-translational regulation of the catalytic and modifier subunits of glutamate cysteine ligase.Mol Aspects Med,30,86-98.
  16. Gipp, .J.J,Chang, C.,Mulcahy, R.T.(1992).Cloning and nucleotide sequence of a full-length cDNA for human liver gamma-glutamylcysteine synthetase.Biochem Biophys Res Commun,185,29-35.
  17. Gipp, J.J.,Bailey, H.H.,Mulcahy, R.T.(1995).Cloning and sequencing of the cDNA for the light subunit of human liver gammaglutamylcysteine synthetase and relative mRNA levels for heavy and light subunits in human normal tissues.Biochem Biophys Res Commun,206,584-589.
  18. Habig, W.H.,Jakoby, W.B.(1981).Assays for differentiation of glutathione S-transferases.Methods Enzymol,77,398-405.
  19. Halliwell, B.,Gutteridge, J.M.C.(2007).Free Radicals in Biology and Medicine.Oxford University Press.
  20. Husen, R.,Pihie, A.H.,Nallappan, M.(2004).Screening for antihyperglycaemic activity in several local herbs of Malaysia.J Ethnopharmacol,95,205-208.
  21. Itoh, K.,Chiba, T.,Takahashi, S.,Ishii, T.,Igarashi, K.,Katoh, Y.,Oyake, T.,Hayashi, N.,Satoh, K.,Hatayama, I.,Yamamoto, M.,Nabeshima, Y.(1997).An Nrf2/small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements.Biochem Biophys Res Commun,236,313-322.
  22. Itoh, K.,Tong, K.I.,Yamamoto, M.(2004).Molecular mechanism activating Nrf-2-keap1 pathway in regulation of adaptive response to electrophiles.Free Radic Biol Med,36,1208-1213.
  23. Jansen, T.,Hortmann, M.,Oelze, M.,Opitz, B.,Steven, S.,Schell, R.,Knorr, M.,Karbach, S.,Schuhmacher, S.,Wenzel, P.,Münzel, T.,Daiber, A.(2010).Conversion of biliverdin to bilirubin by biliverdin reductase contributes to endothelial cell protection by heme oxygenase-1-evidence for direct and indirect antioxidant actions of bilirubin.J Mol Cell Cardiol,49,186-195.
  24. Kosower, N.S.,Kosower, E.M.(1978).The glutathione status of cells.Intl Rev Cytol,54,109-160.
  25. Lawrence, R.A.,Burk, R.F.(1976).Glutathione peroxidase activity in selenium-deficient rat liver.Biochem Biophys Res Commun,71,952-958.
  26. Lii, C.K.,Liu, K.L.,Cheng, Y.P.,Lin, A.H.,Chen, H.W.,Tsai, C.W.(2010).Sulforaphane and α-lipoic acid up-regulate the expression of the pi class of glutathione S-transferase through c-Jun and Nrf2 activation.J Nutr,140,885-892.
  27. Lu, S.C.(2009).Regulation of glutathione synthesis.Mol Aspects Med,30,42-59.
  28. Marklund, S.,Marklund, G.(1974).Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase.Eur J Biochem,47,469-474.
  29. McWalter, G.K.,Higgins, L.G.,McLellan, L.I.,Henderson, C.J.,Song, L.,Thornalley, P.J.,Itoh, K.,Yamamoto, M.,Hayes, J.D.(2004).Transcription factor Nrf2 is essential for induction of NAD(P)H: quinone oxidoreductase 1, glutathione S-transferases, and glutamate cysteine ligase by broccoli seeds and isothiocyanates.J Nutr,134(12 Suppl),3499S-3506.
  30. Owuor, E.D.,Kong, A.N.(2002).Antioxidants and oxidants regulated signal transduction pathways.Biochem Pharmacol,64,765-770.
  31. Pae, H.O.,Lee, Y.C.,Chung, H.T.(2008).Heme oxygenase-1 and carbon monoxide: emerging therapeutic targets in inflammation and allergy.Recent Pat Inflamm Allergy Drug Discov,2,159-165.
  32. Pholphana, N.,Rangkadilok, N.,Thongnest, S.,Ruchirawat, S.,Ruchirawat, M.,Satayavivad, J.(2004).Determination and variation of three active diterpenoids in Andrographis paniculata (Burm.f.) Nees.Phytochem Anal,15,365-371.
  33. Recknagel, R.O.,Ghoshal, A.K.(1966).Quantitative estimation of peroxidative degeneration of rat liver microsomal and mitochondrial lipids after carbon tetrachloride poisoning.Exp Mol Pathol,5,413-426.
  34. Ryter, S.W.,Tyrrell, R.M.(2000).The heme synthesis and degradation pathways: role in oxidant sensitivity. Heme oxygenase has both pro- and antioxidant properties.Free Radic Biol Med,28,289-309.
  35. Singh, R.P.,Banerjee, S.,Rao, A.R.(2001).Modulatory influence of Andrographis paniculata on mouse hepatic and extrahepatic carcinogen metabolizing enzymes and antioxidant status.Phytother Res,15,382-390.
  36. Sun, S.,Zhang, H.,Xue, B.,Wu, Y.,Wang, J.,Yin, Z.,Luo, L.(2006).Protective effect of glutathione against lipopolysaccharide-induced inflammation and mortality in rats.Inflamm Res,55,504-510.
  37. Surh, Y.J.,Kundu, J.K.,Na, H.K.(2008).Nrf2 as a master redox switch in turning on the cellular signaling involved in the induction of cytoprotective genes by some chemopreventive phytochemicals.Planta Med,74,1526-1539.
  38. Tian, J.,Lin, X.,Guan, R.,Xu, J.G.(2004).The effects of hydroxyethyl starch on lung capillary permeability in endotoxic rats and possible mechanisms.Anesth Analg,98,768-774.
  39. Vassort, G.,Turan, B.(2010).Protective role of antioxidants in diabetes-induced cardiac dysfunction.Cardiovasc Toxicol,10,73-86.
  40. Woo, A.Y.,Waye, M.M.,Tsui, S.K.,Yeung, S.T.,Cheng, C.H.(2008).Andrographolide up-regulates cellular-reduced glutathione level and protects cardiomyocytes against hypoxia/reoxygenation injury.J Pharmacol Exp Ther,325,226-235.
  41. Yang, Y.C.,Lii, C.K.,Lin, A.H.,Yeh, Y.W.,Yao, H.T.,Li, C.C.,Liu, K.L.,Chen, H.W.(2011).Induction of glutathione synthesis and heme oxygenase 1 by the flavonoids butein and phloretin is mediated through the ERK/Nrf2 pathway and protects against oxidative stress.Free Radic Biol Med,51,2073-2081.
  42. Yao, H.T.,Lin, J.H.,Chiang, M.T.,Chiang, W.,Luo, M.N.,Lii, C.K.(2011).Suppressive effect of the ethanolic extract of adlay bran on cytochrome P-450 enzymes in rat liver and lungs.J Agric Food Chem,59,4306-4314.
  43. Ye, J.F.,Zhu, H.,Zhou, Z.F.,Xiong, R.B.,Wang, X.W.,Su, L.X.,Luo, B.D.(2011).Protective mechanism of andrographolide against carbon tetrachloride-induced acute liver injury in mice.Biol Pharm Bull,34,1666-1670.
  44. Yet, S.F.,Tian, R.,Layne, M.D.,Wang, Z.Y.,Maemura, K.,Solovyeva, M.,Ith, B.,Melo, L.G.,Zhang, L.,Ingwall, J.S.,Dzau, V.J.,Lee, M.E.,Perrella, M.A.(2001).Cardiac-specific expression of heme oxygenase-1 protects against ischemia and reperfusion injury in transgenic mice.Circ Res,89,168-173.
  45. Yu, A.L.,Lu, C.Y.,Wang, T.S.,Tsai, C.W.,Liu, K.L.,Cheng, Y.P.,Chang, H.C.,Lii, C.K.,Chen, H.W.(2010).Induction of heme oxygenase 1 and inhibition of TNF-α-induced ICAM-1 expression by andrographolide in EA.hy926 cells.J Agric Food Chem,58,7641-7648.
  46. Yu, B.C.,Hung, C.R.,Chen, W.C.,Cheng, J.T.(2003).Antihyperglycemic effect of andrographolide in streptozotocininduced diabetic rats.Planta Med,69,1075-1079.
  47. Zhang, X.F.,Tan, B.K.(2000).Antihyperglycaemic and anti-oxidant properties of Andrographis paniculata in normal and diabetic rats.Clin Exp Pharmacol Physiol,27,358-363.