Aims: This study was carried out to evaluate the hepatoprotective effect of Platycodon grandiflorum (PG) in ethanol (EtOH)-induced liver damage. Methods and Results: PG treatment (both the total extract and saponin fraction) significantly blocked EtOH-induced oxidative stress through the preservation of activities of antioxidant enzymes in HepG2 cells. Furthermore, while the administration of EtOH to C57BL/6 mice for 6 weeks induced liver damage, along with a significant increase in plasma glutamic oxalacetic transaminase, glutamic pyruvic transaminase, hepatic triglyceride and thiobarbituric acid reactive substance levels, PG treatment significantly decreased glutamic oxalacetic transaminase, glutamic pyruvic transaminase, hepatic triglyceride and thiobarbituric acid reactive substance levels compared with the EtOH-treated control group (p < 0.05). Histological observation by hematoxylin-eosin and oil red O staining in the liver showed more effective inhibition of lipid accumulation in PG-treated groups, as compared to the EtOH-treated control group. Additionally, PG treatments appeared to enhance the activities of superoxide dismutase and catalase in the liver (p < 0.05). Conclusion: These results suggest that PG has a protective effect against EtOH-induced oxidative damage, possibly by inhibition of lipid accumulation and peroxidation through the enhancement of the antioxidant defense system. PG might be useful as a therapeutically potent natural ingredient for the prevention of chronic EtOH-induced oxidative stress and liver damage.

Keywords:
Platycodon grandiflorum, Ethanol, Hepatoprotection, Antioxidant effect
1.
Tada A, Kaneiwa Y, Shoji J, Shibata S: Studies on the saponins of the root of Platycodon grandiflorum A. De Candolle. 1. Isolation and the structure of platycodin-D. Chem Pharm Bull (Tokyo) 1975;23:2965–2972.
2.
Han LK, Xu BJ, Kimura Y, Zheng Y, Okuda H: Platycodi radix affects lipid metabolism in mice with high fat diet-induced obesity. J Nutr 2000;130:2760–2764.
3.
Ishii H, Tori K, Tozyo T, Yoshimura Y: Saponins from roots of Platycodon grandiflorum. Part 1. Structure of prosapogenins. J Chem Soc Perkin Trans 1981;1:1928–1933.
4.
Ishii H, Tori K, Tozyo T, Yoshimura Y: Saponins from roots of Platycodon grandiflorum. Part 2. Isolation and structure of new triterpene glycosides J Chem Soc Perkin Trans 1984;11:661–668.
5.
Han SB, Park SH, Lee KH, Lee CW, Lee SH, Kim HC, Kim YS, Lee HS, Kim HM: Polysaccharide isolated from the radix of Platycodon grandiflorum selectively activates B cells and macrophages but not T cells. Int Immunopharmacol 2001;1:1969–1978.
6.
Zhao HL, Cho KH, Ha YW, Jeong TS, Lee WS, Kim YS: Cholesterol-lowering effect of platycodin D in hypercholesterolemic ICR mice. Eur J Pharmacol 2006;537:166–173.
7.
Noh JR, Kim YH, Gang GT, Yang KJ, Kim SK, Ryu SY, Kim YS, Lee CH, Lee HS: Preventative effects of Platycodon grandiflorum treatment on hepatic steatosis in high fat diet-fed C57BL/6 mice. Biol Pharm Bull 2010;33:450–454.
8.
Lee KJ, Choi CY, Chung YC, Kim YS, Ryu SY, Roh SH, Jeong HG: Protective effect of saponins derived from roots of Platycodon grandiflorum on tert-butyl hydroperoxide-induced oxidative hepatotoxicity. Toxicol Lett 2004;147:271–282.
9.
Lee KJ, Choi JH, Kim HG, Han EH, Hwang YP, Lee YC, Chung YC, Jeong HG: Protective effect of saponins derived from the roots of Platycodon grandiflorum against carbon tetrachloride induced hepatotoxicity in mice. Food Chem Toxicol 2008;46:1778–1785.
10.
Lee KJ, You HJ, Park SJ, Kim YS, Chung YC, Jeong TC, Jeong HG: Hepatoprotective effects of Platycodon grandiflorum on acetaminophen-induced liver damage in mice. Cancer Lett 2001;174:73–81.
11.
Khanal T, Choi JH, Hwang YP, Chung YC, Jeong HG: Protective effects of saponins from the root of Platycodon grandiflorum against fatty liver in chronic ethanol feeding via the activation of AMP-dependent protein kinase. Food Chem Toxicol 2009a;47:2749–2754.
12.
Khanal T, Choi JH, Hwang YP, Chung YC, Jeong HG: Saponins isolated from the root of Platycodon grandiflorum protect against acute ethanol-induced hepatotoxicity in mice. Food Chem Toxicol 2009b;47:530–535.
13.
Cederbaum AI, Lu Y, Wu D: Role of oxidative stress in alcohol-induced liver injury. Arch Toxicol 2009;83:519–548.
14.
Lindros KO: Alcoholic liver disease: pathobiological aspects. J Hepatol 1995;23:7–15.
15.
Aebi H: Catalase; in Bergmeyer HU (ed): Methods of Enzymatic Analysis. New York, Academic Press, 1974, pp 673–684.
16.
Marklund S, Marklund G: Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem 1974;47:469–474.
17.
Paglia DE, Valentine WN: Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med 1967;70:158–169.
18.
Pinto RE, Bartley W: The nature of the sex-linked differences in glutathione peroxidase activity and aerobic oxidation of glutathione in male and female rat liver. Biochem J 1969;115:449–456.
19.
Lieber CS, DeCarli LM: The feeding of alcohol in liquid diets: two decades of applications and 1982 update. Alcohol Clin Exp Res 1982;6:523–531.
20.
Bligh EG, Dyer WJ: A rapid method of total lipid extraction and purification. Can J Biochem Physiol 1959;37:911–917.
21.
Ohkawa H, Ohishi N, Yagi K: Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979;95:351–358.
22.
Chirdchupunseree H, Pramyothin P: Protective activity of phyllanthin in ethanol-treated primary culture of rat hepatocytes. J Ethnopharmacol 2010;128:172–176.
23.
Baldi E, Burra P, Plebani M, Salvagnini M: Serum malondialdehyde and mitochondrial aspartate aminotransferase activity as markers of chronic alcohol intake and alcoholic liver disease. Ital J Gastroenterol 1993;25:429–432.
24.
Purohit V, Gao B, Song BJ: Molecular mechanisms of alcoholic fatty liver. Alcohol Clin Exp Res 2009;33:191–205.
25.
Meagher EA, Barry OP, Burke A, Lucey MR, Lawson JA, Rokach J, FitzGerald GA: Alcohol-induced generation of lipid peroxidation products in humans. J Clin Invest 1999;104:805–813.
26.
Sultana R, Raju BS, Sharma V, Reddanna P, Babu PP: Formation of acetaldehyde adducts of glutathione S-transferase A3 in the liver of rats administered alcohol chronically. Alcohol 2005;35:57–66.
27.
You Y, Yoo S, Yoon HG, Park J, Lee YH, Kim S, Oh KT, Lee J, Cho HY, Jun W: In vitro and in vivo hepatoprotective effects of the aqueous extract from Taraxacum officinale (dandelion) root against alcohol-induced oxidative stress. Food Chem Toxicol 2010;48:1632–1637.
28.
Fridovich I: Superoxide anion radical (O–·2 ), superoxide dismutases, and related matters. J Biol Chem 1997;272:18515–18517.
29.
Venukumar MR, Latha MS: Antioxidant effect of Coscinium fenestratum in carbon tetrachloride treated rats. Indian J Physiol Pharmacol 2002;46:223–228.
30.
Muzes G, Deak G, Lang I, Nekam K, Gergely P, Feher J: Effect of the bioflavonoid silymarin on the in vitro activity and expression of superoxide dismutase (SOD) enzyme. Acta Physiol Hung 1991;78:3–9.
31.
Niemela O: Distribution of ethanol-induced protein adducts in vivo: relationship to tissue injury. Free Radic Biol Med 2001;31:1533–1538.
32.
Pal R, Nath R, Gill KD: Lipid peroxidation and antioxidant defense enzymes in various regions of adult rat brain after co-exposure to cadmium and ethanol. Pharmacol Toxicol 1993;73:209–214.
© 2011 S. Karger AG, Basel
2011
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.