Abstract
Two active substances from ginseng fermented using Ganoderma lucidum mycelia were investigated for antiproliferative effects against the human lung cancer cell line A549. The chloroform fraction of fermented ginseng extracts showed a strong antiproliferative effect. This fraction was isolated and purified using silica gel and C18 resin column chromatography and semi-preparative reverse phase HPLC. The structures of isolated compounds were determined using spectroscopic methods (ESI-MS, 1H and 13C NMR). Isolated compounds were identified as ginsenoside compound K and 3-oxo-compound K. Both inhibited A549 cell growth in a dose-dependent manner. Cell viability values for ginsenoside compound K were 74.88, 59.30, 5.76, 5.79, and 6.27% at 6.25, 12.50, 25.00, 50.00, and 100.00 μg/mL, respectively, and ginsenoside 3-oxo-compound K showed values 89.40, 59.62, 6.05, and 4.64% at 3.70, 7.50, 15.00, and 30.00 μg/mL, respectively. Compound K and 3-oxo-compound K from fermented ginseng can be used as natural anti-cancer agents.
Similar content being viewed by others
References
Cheng Y, Lee S, Lin S, Chang W, Chen Y, Tsai N, Liu Y, Tzao C, Yu S, Ham H. Anti-proliferative activity of Bupleurum scrozonerifolium in A549 human lung cancer cells in vitro and in vivo. Cancer Lett. 222: 183–193 (2005)
Manosroi J, Sainakham M, Manosroi W, Manosroi A. Antiproliferative and apoptosis induction activities of extracts from thai medicinal plant recipes selected from MANOSROI II database. J. Ethnopharmacol. 141: 451–459 (2012)
Yu HE, Cho SM, Seo GS, Lee BS, Lee DH, Lee JS. Screening of bioactive compounds from mushroom Pholiota sp. Korean J. Mycol. 34: 15–21 (2006)
Oh SI, Lee MS. Antioxidative and antimutagenic effects of Ganoderma lucidum krast extracts. Korean J. Food Nutr. 18: 54–62 (2005)
Jin H, Jin F, Jin JX, Xu J, Tao TT, Liu J, Huang HJ. Protective effects of Ganoderma lucidum spore on cadmium hepatotoxicity in mice. Food Chem. Toxicol. 52: 171–175 (2012)
Ha CL. The inhibitory effect of the Chinese herb Ganoderma lucidum mycelium on gut immunoglobulin A responses to cholera toxin in mice. Nutr. Res. 23: 691–701 (2003)
Hu SY. The genus Panax (ginseng) in Chinese medicine. Econ. Bot. 30: 11–28 (1976)
Kim DC, Hwang WI, In MJ, Lee SD. Effects of lipid soluble ginseng extract on immune response. J. Ginseng Res. 32: 19–25 (2008)
Lee MH, Choi SW, Kim EJ. Differential anti-carcinogenic effect of mountain cultivated ginseng and ginseng on mouse skin carcinogenesis. J. Korean Soc. Food Sci. Nutr. 41: 462–470 (2012)
Kim HS, Lee MK, Back DY, Hwang SL, Choi KJ, Kim SC. Effects of ginsenosides on the development of morphine-induced tolerance and physical dependence in mice. Korean J. Pharmacogn. 20: 123–127 (1989)
Tchilian EZ, Zhelezarov IE, Hadjiivanova CI. Effect of ginsenoside Rg1 on insulin binding in mice liver and brain membranes. Phytother. Res. 5: 46–48 (1991)
Yang SJ, Woo KS, Yoo JS, Kang TS, Noh YH, Lee JS, Jeong HS. Change of Korean ginseng components with high temperature and pressure treatment. Korean J. Food Sci. Technol. 38: 521–525 (2006)
Joung EM, Kim HY, Hwang IG, Jeong JH, Yu KW, Lee JS, Jeong HS. Changes of antioxidant activities on cultured ginseng with mushroom mycelia during cultivation. J. Korean Soc. Food Sci. Nutr. 39: 1346–1352 (2010)
Joung EM, Hwang IG, Lee HY, Jeong JH, Yu KW, Jeong HS. Changes of saponin and β-glucan content on the cultured ginseng with mushroom mycelia. J. Korean Soc. Food Sci. Nutr. 38: 1084–1089 (2009)
Kim HY, Joung EM, Hwang IG, Jeong JH, Yu KW, Lee JS, Jeong HS. Effect of fermented ginseng extract by mushroom mycelia on antiproliferation of cancer cells. J. Korean Soc. Food Sci. Nutr. 39: 36–41 (2010)
Kim HO, Park MJ, Han JS. Effects of fermented red ginseng supplementation on blood glucose and insulin resistance in type 2 diabetic patients. J. Korean Soc. Food Sci. Nutr. 40: 696–703 (2011)
Bae SH, Lee HS, Kim MR, Kim SY, Kim JM, Suh HJ. Changes of ginsenoside content by mushroom mycelial fermentation in red ginseng extract. J. Ginseng Res. 35: 235–242 (2011)
Ishiyama M, Tominaga H, Shiga M, Sasamoto K, Ohkura Y, Ueno K. A combined assay of cell viability and in vitro cytotoxicity with a highly water-soluble tetrazolium salt, neutral red, and crystal violet. Biol. Pharm. Bull. 19: 1518–1520 (1996)
Park EK, Shin YW, Lee HU, Kim SS, Lee YC, Lee BY, Kim DH. Inhibitory effect of ginsenoside Rb1 and compound K on NO and prostaglandin E2 biosyntheses of RAW 264.7 cells induced by lipopolysaccharide. Biol. Pharm. Bull. 28: 652–656 (2005)
Han GC, Ko SK, Sung JH, Chung SH. Compound K enhances insulin secretion with beneficial metabolic effects in db/db mice. J. Agr. Food Chem. 55: 10641–10648 (2007)
Surh YJ, Na HK, Lee JY, Keum YS. Molecular mechanisms underlying anti-tumor promoting activities of heat-processed Panax ginseng C.A. Meyer. J. Korean Med. Sci. 16: S38–S41 (2001)
Choi KS, Choi CH. Proapoptotic ginsenosides compound K and Rh2 enhance Fas-induced cell death of human astrocytoma cells through distinct apoptotic signaling pathways. Cancer Res. Treat. 41: 36–44 (2009)
Choi YS, Han GC, Han EJ, Park KJ, Sung JH, Chung SH. Effects of compound K on insulin secretion and carbohydrate metabolism. J. Ginseng Res. 31: 79–85 (2007)
Yoon SH, Han EJ, Sung JH, Chung SH. Anti-diabetic effects of compound K versus metformin versus compound K-metformin combination therapy in diabetic db/db mice. Biol. Pharm. Bull. 30: 2196–2200 (2007)
Li W, Zhang M, Gu J, Meng ZJ, Zhao LC, Zheng YN, Chen L, Yang GL. Hypoglycemic effect of protopanaxadiol-type ginsenosides and compound K on type 2 diabetes mice induced by high-fat diet combining with streptozotocin via suppression of hepatic gluconeogenesis. Fitoterapia 83: 192–198 (2012)
Shin YW, Kim DH. Antipruritic effect of ginsenoside Rb1 and compound K in scratching behavior mouse models. J. Pharmacol. Sci. 99: 83–88 (2005)
Lee HU, Bae EA, Han MJ, Kim NJ, Kim DH. Hepatoprotective effect of ginsenoside Rb1 and compound K on tert-butyl hydroperoxide-induced liver injury. Liver Int. 25: 1069–1073 (2005)
Park DM, Yoon MC. Compound K, a novel ginsenoside metabolite, inhibits adipocyte differentiation in 3T3-L1 cells: Involvement of angiogenesis and MMPs. Biochem. Bioph. Res. Co. 422: 263–267 (2012)
Chen GT, Yang M, Song Y, Lu ZQ, Zhang JQ, Huang HL, Wu LI, Guo DA. Microbial transformation of ginsenoside Rb1 by Acremonium strictum. Appl. Microbiol. Biot. 77: 1345–1350 (2008)
Quan LH, Liang ZQ, Kim HB, Kim SH, Kim SY, Noh YD, Yang DC. Conversion of ginsenoside Rd to compound K by crude enzymes extracted from Lactobacillus brevis LH8. J. Ginseng Res. 32: 226–231 (2008)
Noh KH, Son JW, Kim HJ, Oh DK. Ginsenoside compound K production from ginseng root extract by a thermostable betaglycosidase from Sulfolobus solfataricus. Biosci. Biotech. Bioch. 73: 316–321 (2009)
Bae EA, Kim NY, Han MJ, Choo MK, Kim DH. Transformation of ginsenosides to compound K (IH-901) by lactic acid bacteria of human intestine. J. Microbiol. Biotechn. 13: 9–14 (2003)
Piao JY, Kim YJ, Quan LH, Yang DU, Min JW, Son SH, Kim SM, Yang DC. Bioconversion of ginsenoside Rb1 to compound K using Leuconostoc lactis DC201. Korean J. Plant Res. 24: 712–718 (2011)
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Jang, G.Y., Joung, E.M., Lee, S.H. et al. Isolation and identification of antiproliferative substances from ginseng fermented using Ganoderma lucidum mycelia. Food Sci Biotechnol 24, 567–574 (2015). https://doi.org/10.1007/s10068-015-0074-3
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10068-015-0074-3