Therapeutic Effects of Korean Red Ginseng Extract in Egyptian Patients with Chronic Liver Diseases

  • Abdel-Wahhab, Mosaad A. (Food Toxicology & Contaminants Department, National Research Centre) ;
  • Gamil, Khaled (National Liver Institute, Monoufia University) ;
  • El-Kady, Ahmed A. (Food Toxicology & Contaminants Department, National Research Centre) ;
  • El-Nekeety, Aziza A. (Food Toxicology & Contaminants Department, National Research Centre) ;
  • Naguib, Khayria M. (Food Toxicology & Contaminants Department, National Research Centre)
  • Received : 2010.10.18
  • Accepted : 2011.02.07
  • Published : 2011.03.29


Hepatocellular carcinoma (HCC) is the fi fth most common malignancy in the world and complicates liver cirrhosis related to hepatitis C virus (HCV) in many cases. We evaluated the therapeutic effect of Korean red ginseng extract (KGE) in patients with chronic liver diseases. Thirty male and female patients with HCC and another thirty with liver cirrhosis were included. Each category was divided into two groups; the first was used as control group, and received medical therapy only and the second group received the medical therapy supplemented with KGE capsules. The treated group with HCC received three KGE capsules/day (900 mg) while the treated group with HCV received two KGE capsules/day (600 mg) for 11 weeks along with their medical therapy. All patients were subjected to clinical examination and laboratory investigations, including liver function tests (at baseline, after 6 weeks of treatment and at the end of the study) and abdominal ultrasonography. Patients showing focal hepatic lesions were subjected to triphasic spiral abdominal computerized tomography and alpha-fetoprotein (AFP). HCV RNA was determined quantitatively by Roche for patients in the HCV group. Results showed that the medical therapy alone failed to normalize the liver enzymes or decrease the virus concentration. KGE administration induced a significant improvement in liver function tests, decreased the tumor marker (AFP) levels, and decreased the viral titers in HCV patients. Thus, KGE demonstrated powerful therapeutic effects against HCV and liver cancer.



  1. El-Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology 2007;132:2557-2576.
  2. Velazquez RF, Rodriguez M, Navascues CA, Linares A, Perez R, Sotorrios NG, Martinez I, Rodrigo L. Prospective analysis of risk factors for hepatocellular carcinoma in patients with liver cirrhosis. Hepatology 2003;37:520-527.
  3. Rahman El-Zayadi A, Abaza H, Shawky S, Mohamed MK, Selim OE, Badran HM. Prevalence and epidemiological features of hepatocellular carcinoma in Egypt: a single center experience. Hepatol Res 2001;19:170-179.
  4. Farazi PA, DePinho RA. Hepatocellular carcinoma pathogenesis: from genes to environment. Nat Rev Cancer 2006;6:674-687.
  5. Soldati F. Panax ginseng: standardization and biological activity. In: Cutler SJ, Cutler HG eds. Biologically active natural products: pharmaceuticals. Boca Raton (FL): CRC Press, 2000. p. 209-232.
  6. Barnes P, Powell-Griner E, McFann K, Nahin R. Complementary and alternative medicine use among adults: United States, 2002. Bethesda (MD): National Center for Complementary and Alternative Medicine, 2004.
  7. Hasegawa H, Sung JH, Matsumiya S, Uchiyama M. Main ginseng saponin metabolites formed by intestinal bacteria. Planta Med 1996;62:453-457.
  8. Hasegawa H, Sung JH, Matsumiya S, Uchiyama M, Inouye Y, Kasai R, Yamasaki K. Reversal of daunomycin and vinblastine resistance in multidrug-resistant P388 leukemia in vitro through enhanced cytotoxicity by triterpenoids. Planta Med 1995;61:409-413.
  9. Lee SJ, Sung JH, Lee SJ, Moon CK, Lee BH. Antitumor activity of a novel ginseng saponin metabolite in human pulmonary adenocarcinoma cells resistant to cisplatin. Cancer Lett 1999;144:39-43.
  10. Lee BM, Lee SK, Kim HS. Inhibition of oxidative DNA damage, 8-OHdG, and carbonyl contents in smokers treated with antioxidants (vitamin E, vitamin C, beta-carotene and red ginseng). Cancer Lett 1998;132:219-227.
  11. Lee SJ, Ko WG, Kim JH, Sung JH, Moon CK, Lee BH. Induction of apoptosis by a novel intestinal metabolite of ginseng saponin via cytochrome c-mediated activation of caspase-3 protease. Biochem Pharmacol 2000;60:677-685.
  12. Choi HH, Jong HS, Park JH, Choi S, Lee JW, Kim TY, Otsuki T, Namba M, Bang YJ. A novel ginseng saponin metabolite induces apoptosis and down-regulates fi broblast growth factor receptor 3 in myeloma cells. Int J Oncol 2003;23:1087-1093.
  13. Dienstag JL, McHutchison JG. American Gastroenterological Association technical review on the management of hepatitis C. Gastroenterology 2006;130:231-264.
  14. Davis GL, Albright JE, Cook SF, Rosenberg DM. Projecting future complications of chronic hepatitis C in the United States. Liver Transpl 2003;9:331-338.
  15. Esteban JI, Sauleda S, Quer J. The changing epidemiology of hepatitis C virus infection in Europe. J Hepatol 2008;48:148-162.
  16. Martinez-Bauer E, Forns X, Armelles M, Planas R, Sola R, Vergara M, Fabregas S, Vega R, Salmeron J, Diago M, et al. Hospital admission is a relevant source of hepatitis C virus acquisition in Spain. J Hepatol 2008;48:20-27.
  17. Kubitschke A, Bader C, Tillmann HL, Manns MP, Kuhn S, Wedemeyer H. Injuries from needles contaminated with hepatitis C virus: how high is the risk of seroconversion for medical personnel really? Internist (Berl) 2007;48:1165-1172.
  18. Wiegand J, Buggisch P, Boecher W, Zeuzem S, Gelbmann CM, Berg T, Kauffmann W, Kallinowski B, Cornberg M, Jaeckel E, et al. Early monotherapy with pegylated interferon alpha-2b for acute hepatitis C infection: the HEP-NET acute-HCV-II study. Hepatology 2006;43:250-256.
  19. Kamal SM, Fouly AE, Kamel RR, Hockenjos B, Al Tawil A, Khalifa KE, He Q, Koziel MJ, El Naggar KM, Rasenack J, et al. Peginterferon alfa-2b therapy in acute hepatitis C: impact of onset of therapy on sustained virologic response. Gastroenterology 2006;130:632-638.
  20. Kamal SM, Moustafa KN, Chen J, Fehr J, Abdel Moneim A, Khalifa KE, El Gohary LA, Ramy AH, Madwar MA, Rasenack J, et al. Duration of peginterferon therapy in acute hepatitis C: a randomized trial. Hepatology 2006;43:923-931.
  21. Orland JR, Wright TL, Cooper S. Acute hepatitis C. Hepatology 2001;33:321-327.
  22. GenevaWorld Health Organization. Hepatitis C. Geneva: World Health Organization, 2000.
  23. Santantonio T, Wiegand J, Gerlach JT. Acute hepatitis C: current status and remaining challenges. J Hepatol 2008;49:625-633.
  24. Howe HL, Wingo PA, Thun MJ, Ries LA, Rosenberg HM, Feigal EG, Edwards BK. Annual report to the nation on the status of cancer (1973 through 1998), featuring cancers with recent increasing trends. J Natl Cancer Inst 2001;93:824-842.
  25. Ogunbiyi JO. Hepatocellular carcinoma in the developing world. Semin Oncol 2001;28:179-187.
  26. Taylor-Robinson SD, Foster GR, Arora S, Hargreaves S, Thomas HC. Increase in primary liver cancer in the UK, 1979-94. Lancet 1997;350:1142-1143.
  27. El-Serag HB, Mason AC. Rising incidence of hepatocellular carcinoma in the United States. N Engl J Med 1999;340:745-750.
  28. Abdel-Wahhab MA, Hassan NS, El-Kady AA, Khadrawy YA, El-Nekeety AA, Mohamed SR, Sharaf HA, Mannaa FA. Red ginseng extract protects against afl atoxin B1 and fumonisins-induced hepatic pre-cancerous lesions in rats. Food Chem Toxicol 2010;48:733-742.
  29. World Gastroenterology Organisation practice guideline: management of acute viral hepatitis. Available from:
  30. Mondelli MU, Cerino A, Cividini A. Acute hepatitis C: diagnosis and management. J Hepatol 2005;42 Suppl(1):S108-S114.
  31. Heller T, Rehermann B. Acute hepatitis C: a multifaceted disease. Semin Liver Dis 2005;25:7-17.
  32. Abdel-Wahhab MA, Amer HA, Hassan NS, Hassan AM, Naguib K. Effects of garlic and cabbage extracts on fumonisin-induced toxicity in rats. J Egypt Soc Toxicol 2002;26:1-12.
  33. Abdel-Wahhab MA, Aly SE. Antioxidants and radical scavenging properties of vegetable extracts in rats fed afl atoxincontaminated diet. J Agric Food Chem 2003;51:2409-2414.
  34. Abdel-Wahhab MA, Aly SE. Antioxidant property of Nigella sativa (black cumin) and Syzygium aromaticum (clove) in rats during afl atoxicosis. J Appl Toxicol 2005;25:218-223.
  35. Palazzi C, D’Angelo S, Olivieri I. Hepatitis C virus-related arthritis. Autoimmun Rev 2008;8:48-51.
  36. Attele AS, Wu JA, Yuan CS. Ginseng pharmacology: multiple constituents and multiple actions. Biochem Pharmacol 1999;58:1685-1693.
  37. Shin HR, Kim JY, Yun TK, Morgan G, Vainio H. The cancerpreventive potential of Panax ginseng: a review of human and experimental evidence. Cancer Causes Control 2000;11:565-576.
  38. Park EK, Choo MK, Han MJ, Kim DH. Ginsenoside Rh1 possesses antiallergic and anti-inflammatory activities. Int Arch Allergy Immunol 2004;133:113-120.
  39. Kobashi K, Akao T, Hattori M, Namba T. Metabolism of drugs by intestinal bacteria. Bifidobact Microflora 1992;11:9-23.
  40. Kobashi K, Akao T. Relation of intestinal bacteria to pharmacological effects of glycosides. Biosci Microflora 1997;16:1-7.
  41. Wakabayashi C, Hasegawa H, Murata J, Saiki I. In vivo antimetastatic action of ginseng protopanaxadiol saponins is based on their intestinal bacterial metabolites after oral administration. Oncol Res 1997;9:411-417.
  42. Wakabayashi C, Hasegawa H, Murata J, Saiki I. The expression of in vivo antimetastatic effect of ginseng protopanaxatriol saponins is mediated by their intestinal bacterial metabolites after oral administration. J Tradit Med 1997;14:180-185.
  43. Hasegawa H, Suzuki R, Nagaoka T, Tezuka Y, Kadota S, Saiki I. Prevention of growth and metastasis of murine melanoma through enhanced natural-killer cytotoxicity by fatty acid-conjugate of protopanaxatriol. Biol Pharm Bull 2002;25:861-866.
  44. Yun TK. Panax ginseng: a non-organ-specific cancer preventive? Lancet Oncol 2001;2:49-55.
  45. Bae EA, Park SY, Kim DH. Constitutive beta-glucosidases hydrolyzing ginsenoside Rb1 and Rb2 from human intestinal bacteria. Biol Pharm Bull 2000;23:1481-1485.
  46. Bae EA, Choo MK, Park EK, Park SY, Shin HY, Kim DH. Metabolism of ginsenoside R(c) by human intestinal bacteria and its related antiallergic activity. Biol Pharm Bull 2002;25:743-747.
  47. Akao T, Kanaoka M, Kobashi K. Appearance of compound K, a major metabolite of ginsenoside Rb1 by intestinal bacteria, in rat plasma after oral administration: measurement of compound K by enzyme immunoassay. Biol Pharm Bull 1998;21:245-249.
  48. Akao T, Kida H, Kanaoka M, Hattori M, Kobashi K. Intestinal bacterial hydrolysis is required for the appearance of compound K in rat plasma after oral administration of ginsenoside Rb1 from Panax ginseng. J Pharm Pharmacol 1998;50:1155-1160.
  49. Hasegawa H, Matsumiya S, Uchiyama M, Kurokawa T, Inouye Y, Kasai R, Ishibashi S, Yamasaki K. Inhibitory effect of some triterpenoid saponins on glucose transport in tumor cells and its application to in vitro cytotoxic and antiviral activities. Planta Med 1994;60:240-243.
  50. Hasegawa H, Sung JH, Huh JH. Ginseng intestinal bacterial metabolite IH901 as a new anti-metastatic agent. Arch Pharm Res 1997;20:539-544.
  51. Kim SE, Lee YH, Park JH, Lee SK. Ginsenoside-Rs4, a new type of ginseng saponin concurrently induces apoptosis and selectively elevates protein levels of p53 and p21WAF1 in human hepatoma SK-HEP-1 cells. Eur J Cancer 1999;35:507-511.
  52. Wakabayashi C, Murakami K, Hasegawa H, Murata J, Saiki I. An intestinal bacterial metabolite of ginseng protopanaxadiol saponins has the ability to induce apoptosis in tumor cells. Biochem Biophys Res Commun 1998;246:725-730.
  53. Oh SH, Yin HQ, Lee BH. Role of the Fas/Fas ligand death receptor pathway in ginseng saponin metabolite-induced apoptosis in HepG2 cells. Arch Pharm Res 2004;27:402-406.
  54. Yim HW, Jong HS, Kim TY, Choi HH, Kim SG, Song SH, Kim J, Ko SG, Lee JW, Kim TY, et al. Cyclooxygenase-2 inhibits novel ginseng metabolite-mediated apoptosis. Cancer Res 2005;65:1952-1960.
  55. Ming YL, Song G, Chen LH, Zheng ZZ, Chen ZY, Ouyang GL, Tong QX. Anti-proliferation and apoptosis induced by a novel intestinal metabolite of ginseng saponin in human hepatocellular carcinoma cells. Cell Biol Int 2007;31:1265-1273.
  56. Herr I, Debatin KM. Cellular stress response and apoptosis in cancer therapy. Blood 2001;98:2603-2614.
  57. Liu X, Kim CN, Yang J, Jemmerson R, Wang X. Induction of apoptotic program in cell-free extracts: requirement for dATP and cytochrome c. Cell 1996;86:147-157.
  58. Srinivasula SM, Ahmad M, Fernandes-Alnemri T, Alnemri ES. Autoactivation of procaspase-9 by Apaf-1-mediated oligomerization. Mol Cell 1998;1:949-957.
  59. Slee EA, Harte MT, Kluck RM, Wolf BB, Casiano CA, Newmeyer DD, Wang HG, Reed JC, Nicholson DW, Alnemri ES, et al. Ordering the cytochrome c-initiated caspase cascade: hierarchical activation of caspases-2, -3, -6, -7, -8, and -10 in a caspase-9-dependent manner. J Cell Biol 1999;144:281-292.
  60. Oh SH, Lee BH. A ginseng saponin metabolite-induced apoptosis in HepG2 cells involves a mitochondria-mediated pathway and its downstream caspase-8 activation and Bid cleavage. Toxicol Appl Pharmacol 2004;194:221-229.
  61. Adams JM, Cory S. The Bcl-2 protein family: arbiters of cell survival. Science 1998;281:1322-1326.
  62. Gross A, McDonnell JM, Korsmeyer SJ. BCL-2 family members and the mitochondria in apoptosis. Genes Dev 1999;13:1899-1911.
  63. Korsmeyer SJ, Wei MC, Saito M, Weiler S, Oh KJ, Schlesinger PH. Pro-apoptotic cascade activates BID, which oligomerizes BAK or BAX into pores that result in the release of cytochrome c. Cell Death Differ 2000;7:1166-1173.
  64. Jones PJ, Ntanios FY, Raeini-Sarjaz M, Vanstone CA. Cholesterol-lowering efficacy of a sitostanol-containing phytosterol mixture with a prudent diet in hyperlipidemic men. Am J Clin Nutr 1999;69:1144-1150.
  65. Cleghorn CL, Skeaff CM, Mann J, Chisholm A. Plant sterol-enriched spread enhances the cholesterol-lowering potential of a fat-reduced diet. Eur J Clin Nutr 2003;57:170-176.
  66. Navarro A, De las Heras B, Villar A. Anti-infl ammatory and immunomodulating properties of a sterol fraction from Sideritis foetens Clem. Biol Pharm Bull 2001;24:470-473.
  67. Aboutabl EA, Nassar MI, Elsakhawy FM, Maklad YA, Osman AF, El-Khrisy EA. Phytochemical and pharmacological studies on Sideritis taurica Stephan ex Wild. J Ethnopharmacol 2002;82:177-184.
  68. Villasenor IM, Angelada J, Canlas AP, Echegoyen D. Bioactivity studies on beta-sitosterol and its glucoside. Phytother Res 2002;16:417-421.
  69. Yun TK, Lee YS, Choi KJ, Lee YH, Yun HY. Anticarcinogenicity of various ginseng fractions and components in red ginseng using Yun’s anticarcinogenicity test model. J Korean Assoc Cancer Prev 2000;5:186-192.
  70. Nishino H, Tokuda H, Ii T, Takemura M, Kuchide M, Kanazawa M, Mou XY, Bu P, Takayasu J, Onozuka M, et al. Cancer chemoprevention by ginseng in mouse liver and other organs. J Korean Med Sci 2001;16 Suppl:S66-S69.
  71. Antonelli A, Ferri C, Galeazzi M, Giannitti C, Manno D, Mieli-Vergani G, Menegatti E, Olivieri I, Puoti M, Palazzi C, et al. HCV infection: pathogenesis, clinical manifestations and therapy. Clin Exp Rheumatol 2008;26(1 Suppl 48):S39-S47.
  72. Farinati F, Cardin R, Bortolami M, Burra P, Russo FP, Rugge M, Guido M, Sergio A, Naccarato R. Hepatitis C virus: from oxygen free radicals to hepatocellular carcinoma. J Viral Hepat 2007;14:821-829.
  73. Osman HG, Gabr OM, Lotfy S, Gabr S. Serum levels of bcl-2 and cellular oxidative stress in patients with viral hepatitis. Indian J Med Microbiol 2007;25:323-329.
  74. Abdel-Wahhab MA, Ahmed HH. Protective effect of Korean Panax ginseng against chromium VI toxicity and free radicals generation in rats. J Ginseng Res 2004;28:11-17.
  75. Yun TK, Choi SY, Yun HY. Epidemiological study on cancer prevention by ginseng: are all kinds of cancers preventable by ginseng? J Korean Med Sci 2001;16 Suppl:S19-S27.

Cited by

  1. Red Ginseng Marc Oil Inhibits iNOS and COX-2 via NFκB and p38 Pathways in LPS-Stimulated RAW 264.7 Macrophages vol.17, pp.12, 2012,
  2. Pharmacological Effects of Ginseng on Liver Functions and Diseases: A Minireview vol.2012, pp.1741-4288, 2012,
  3. Investigation of metabolite alteration in dimethylnitrosamine-induced liver fibrosis by GC–MS vol.5, pp.1, 2013,
  4. Efficacy of Korean Red Ginseng in the Treatment of Alopecia Areata vol.36, pp.4, 2011,
  5. 포르말린으로 유도된 안면통증에 대한 홍삼추출물의 항염증 효과 vol.15, pp.9, 2011,
  6. Histological, ultrastructural, and biochemical study on the possible role of Panax ginseng in ameliorating liver injury induced by Lambda cyhalotherin vol.9, pp.1, 2011,
  7. Ginseng Consumption Possible Effect on Liver Cancer: A Meta-Analysis vol.73, pp.9, 2011,
  8. Panax Ginseng alleviates thioacetamide-induced liver injury in ovariectomized rats: Crosstalk between inflammation and oxidative stress vol.16, pp.11, 2011,