Correlation of cultivation time of Panax ginseng with metabolic profiles of nine ginsenosides and mRNA expression of genes encoding major biosynthetic enzymes

详细信息    查看全文

• 作者：Jia Liu ; Yang Liu ; Zhong-Hua Zhang ; Yuan-Gang Zu…
• 关键词：Araliaceae ; HPLC ; Panax ginseng ; Cultivation time ; Ginsenosides ; Gene expression
• 刊名：Acta Physiologiae Plantarum
• 出版年：2016
• 出版时间：February 2016
• 年：2016
• 卷：38
• 期：2
• 全文大小：2,582 KB
• 参考文献：Bienert MD, Siegmund SE, Drozak A, Trombik T, Bultreys A, Baldwin IT, Boutry M (2012) A pleiotropic drug resistance transporter in Nicotiana tabacum is involved in defense against the herbivore Manduca sexta. Plant J 72:745–757CrossRef PubMed
  Bonfill M, Casals I, Palazon J, Mallol A, Morales C (2002) Improved high performance liquid chromatographic determination of ginsenosides in Panax ginseng-based pharmaceuticals using a diol column. Biomed Chromatogr 16:68–72CrossRef PubMed
  Chan PC, Huff J (2012) Hexane fraction of American ginseng suppresses colitis and colon cancer. Cancer Prev Res 5:982 (author reply 983) CrossRef
  Cho IH (2012) Effects of Panax ginseng in neurodegenerative diseases. J Ginseng Res 36:342–353PubMedCentral CrossRef PubMed
  Cho J, Park W, Lee S, Ahn W, Lee Y (2004) Ginsenoside-Rb1 from Panax ginseng C.A. Meyer activates estrogen receptor-alpha and -beta, independent of ligand binding. J Clin Endocrinol Metab 89:3510–3515CrossRef PubMed
  Court WE (2000) Ginseng: the history of an insignificant plant. Pharm Hist (Lond) 30:38–44
  Crouzet J, Trombik T, Fraysse AS, Boutry M (2006) Organization and function of the plant pleiotropic drug resistance ABC transporter family. FEBS Lett 580:1123–1130CrossRef PubMed
  Dou DQ, Chen YJ, Liang LH, Pang FG, Shimizu N, Takeda T (2001) Six new dammarane-type triterpene saponins from the leaves of Panax ginseng. Chem Pharm Bull (Tokyo) 49:442–446CrossRef
  Eilenberg H, Shechter I (1987) Regulation of squalene epoxidase activity and comparison of catalytic properties of rat liver and Chinese hamster ovary cell-derived enzymes. J Lipid Res 28:1398–1404PubMed
  Gardiner DM, Stephens AE, Munn AL, Manners JM (2013) An ABC pleiotropic drug resistance transporter of Fusarium graminearum with a role in crown and root diseases of wheat. FEMS Microbiol Lett 348:36–45CrossRef PubMed
  Godio RP, Fouces R, Martin JF (2007) A squalene epoxidase is involved in biosynthesis of both the antitumor compound clavaric acid and sterols in the basidiomycete H. sublateritium. Chem Biol 14:1334–1346CrossRef PubMed
  Han JY, Kwon YS, Yang DC, Jung YR, Choi YE (2006) Expression and RNA interference-induced silencing of the dammarenediol synthase gene in Panax ginseng. Plant Cell Physiol 47:1653–1662CrossRef PubMed
  Han JY, In JG, Kwon YS, Choi YE (2010) Regulation of ginsenoside and phytosterol biosynthesis by RNA interferences of squalene epoxidase gene in Panax ginseng. Phytochemistry 71:36–46CrossRef PubMed
  Han JY, Hwang HS, Choi SW, Kim HJ, Choi YE (2012) Cytochrome P450 CYP716A53v2 catalyzes the formation of protopanaxatriol from protopanaxadiol during ginsenoside biosynthesis in Panax ginseng. Plant Cell Physiol 53:1535–1545CrossRef PubMed
  Haralampidis K, Trojanowska M, Osbourn AE (2002) Biosynthesis of triterpenoid saponins in plants. Adv Biochem Eng Biotechnol 75:31–49PubMed
  Hu W, Liu N, Tian Y, Zhang L (2013) Molecular cloning, expression, purification, and functional characterization of dammarenediol synthase from Panax ginseng. Biomed Res Int 2013:285740PubMedCentral PubMed
  Huang C, Qian ZG, Zhong JJ (2013) Enhancement of ginsenoside biosynthesis in cell cultures of Panax ginseng by N, N′-dicyclohexylcarbodiimide elicitation. J Biotechnol 165:30–36CrossRef PubMed
  Joo KM, Lee JH, Jeon HY, Park CW, Hong DK, Jeong HJ, Lee SJ, Lee SY, Lim KM (2010) Pharmacokinetic study of ginsenoside Re with pure ginsenoside Re and ginseng berry extracts in mouse using ultra performance liquid chromatography/mass spectrometric method. J Pharm Biomed Anal 51:278–283CrossRef PubMed
  Kim YuA, Akoev VR, Elemesov RE (2000) Hyperosmotic hemolysis and antihemolytic activity of the saponin fraction and triterpene glycosides from Panax ginseng C. A. Meyer. Membr Cell Biol 14:237–251PubMed
  Kim TD, Han JY, Huh GH, Choi YE (2011) Expression and functional characterization of three squalene synthase genes associated with saponin biosynthesis in Panax ginseng. Plant Cell Physiol 52:125–137CrossRef PubMed
  Lee MH, Jeong JH, Seo JW, Shin CG, Kim YS, In JG, Yang DC, Yi JS, Choi YE (2004) Enhanced triterpene and phytosterol biosynthesis in Panax ginseng overexpressing squalene synthase gene. Plant Cell Physiol 45:976–984CrossRef PubMed
  Lee M, Lee K, Lee J, Noh EW, Lee Y (2005) AtPDR12 contributes to lead resistance in Arabidopsis. Plant Physiol 138:827–836PubMedCentral CrossRef PubMed
  Lee MH, Han JY, Kim HJ, Kim YS, Huh GH, Choi YE (2012) Dammarenediol-II production confers TMV tolerance in transgenic tobacco expressing Panax ginseng dammarenediol-II synthase. Plant Cell Physiol 53:173–182CrossRef PubMed
  Lee Y, Kim KT, Kim SS, Hur J, Ha SK, Cho CW, Choi SY (2014) Inhibitory effects of ginseng seed on melanin biosynthesis. Pharmacogn Mag 10:S272–S275PubMedCentral CrossRef PubMed
  Ng TB, Wang H (2001) Panaxagin, a new protein from Chinese ginseng possesses anti-fungal, anti-viral, translation-inhibiting and ribonuclease activities. Life Sci 68:739–749CrossRef PubMed
  Nguyen HT, Song GY, Kim JA, Hyun JH, Kang HK, Kim YH (2010) Dammarane-type saponins from the flower buds of Panax ginseng and their effects on human leukemia cells. Bioorg Med Chem Lett 20:309–314CrossRef PubMed
  Pan YJ, Liu J, Guo XR, Zu YG, Tang ZH (2015) Gene transcript profiles of the TIA biosynthetic pathway in response to ethylene and copper reveal their interactive role in modulating TIA biosynthesis in Catharanthus roseus. Protoplasma 252:813–824CrossRef PubMed
  Qiu F, Ma ZZ, Xu SX, Yao XS, Che CT, Chen YJ (2001) A pair of 24-hydroperoxyl epimeric dammarane saponins from flower-buds of Panax ginseng. J Asian Nat Prod Res 3:235–240CrossRef PubMed
  Rhim H, Kim H, Lee DY, Oh TH, Nah SY (2002) Ginseng and ginsenoside Rg3, a newly identified active ingredient of ginseng, modulate Ca2+ channel currents in rat sensory neurons. Eur J Pharmacol 436:151–158CrossRef PubMed
  Sathiyamoorthy S, In JG, Gayathri S, Kim YJ, Yang D (2010a) Gene ontology study of methyl jasmonate-treated and non-treated hairy roots of Panax ginseng to identify genes involved in secondary metabolic pathway. Genetika 46:932–939PubMed
  Sathiyamoorthy S, In JG, Gayathri S, Kim YJ, Yang DC (2010b) Generation and gene ontology based analysis of expressed sequence tags (EST) from a Panax ginseng C. A. Meyer roots. Mol Biol Rep 37:3465–3472CrossRef PubMed
  Shibata S (2001) Chemistry and cancer preventing activities of ginseng saponins and some related triterpenoid compounds. J Korean Med Sci 16(Suppl):S28–S37PubMedCentral CrossRef PubMed
  Shin HR, Kim JY, Yun TK, Morgan G, Vainio H (2000) The cancer-preventive potential of Panax ginseng: a review of human and experimental evidence. Cancer Causes Control 11:565–576CrossRef PubMed
  Sritularak B, Morinaga O, Yuan CS, Shoyama Y, Tanaka H (2009) Quantitative analysis of ginsenosides Rb1, Rg1, and Re in American ginseng berry and flower samples by ELISA using monoclonal antibodies. J Nat Med 63:360–363CrossRef PubMed
  Tansakul P, Shibuya M, Kushiro T, Ebizuka Y (2006) Dammarenediol-II synthase, the first dedicated enzyme for ginsenoside biosynthesis, in Panax ginseng. FEBS Lett 580:5143–5149CrossRef PubMed
  Vanhaelen-Fastre RJ, Faes ML, Vanhaelen MH (2000) High-performance thin-layer chromatographic determination of six major ginsenosides in Panax ginseng. J Chromatogr A 868:269–276CrossRef PubMed
  Wang BX, Zhou QL, Yang M, Wang Y, Cui ZY, Liu YQ, Ikejima T (2003) Hypoglycemic activity of ginseng glycopeptide. Acta Pharmacol Sin 24:50–54PubMed
  Xi J, Xu P, Xiang CB (2012) Loss of AtPDR11, a plasma membrane-localized ABC transporter, confers paraquat tolerance in Arabidopsis thaliana. Plant J 69:782–791CrossRef PubMed
  Xie JT, Wang CZ, Zhang B, Mehendale SR, Li XL, Sun S, Han AH, Du W, He TC, Yuan CS (2009) In vitro and in vivo anticancer effects of American ginseng berry: exploring representative compounds. Biol Pharm Bull 32:1552–1558CrossRef PubMed
  Yeo CR, Yang C, Wong TY, Popovich DG (2011) A quantified ginseng (Panax ginseng C.A. Meyer) extract influences lipid acquisition and increases adiponectin expression in 3T3-L1 cells. Molecules 16:477–492CrossRef PubMed
  Zhai WM, Yuan YS, Zhou YX, Wei L (2001) HPLC fingerprints identification of Panax ginseng C. A. Mey., P. quinquefolin L. and P. notoginseng (Burk. F. H. Chen). Zhongguo Zhong Yao Za Zhi 26:481–482PubMed
  Zhang C, Yu H, Bao Y, An L, Jin F (2001) Purification and characterization of ginsenoside-beta-glucosidase from ginseng. Chem Pharm Bull (Tokyo) 49:795–798CrossRef
  Zhang R, Huang J, Zhu J, Xie X, Tang Q, Chen X, Luo J, Luo Z (2013) Isolation and characterization of a novel PDR-type ABC transporter gene PgPDR3 from Panax ginseng C.A. Meyer induced by methyl jasmonate. Mol Biol Rep 40:6195–6204CrossRef PubMed
  Zhao JM, Li N, Zhang H, Wu CF, Piao HR, Zhao YQ (2011) Novel dammarane-type sapogenins from Panax ginseng berry and their biological activities. Bioorg Med Chem Lett 21:1027–1031CrossRef PubMed
  Zhu GY, Li YW, Hau DK, Jiang ZH, Yu ZL, Fong WF (2011) Protopanaxatriol-type ginsenosides from the root of Panax ginseng. J Agric Food Chem 59:200–205CrossRef PubMed
  
• 作者单位：Jia Liu (1)
  Yang Liu (1)
  Zhong-Hua Zhang (1)
  Yuan-Gang Zu (1)
  Zhong-Hua Tang (1)
  Thomas Efferth (2)
  
  1. Key Laboratory of Plant Ecology, Northeast Forestry University, Harbin, 150040, China
  2. Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, 55128, Mainz, Germany
  
• 刊物主题：Plant Physiology; Plant Genetics & Genomics; Plant Biochemistry; Plant Pathology; Plant Anatomy/Development; Agriculture;
• 出版者：Springer Berlin Heidelberg
• ISSN：1861-1664

文摘

Ginseng (Panax ginseng C. A. Meyer) is one of the most important Chinese medicinal herbs. This medicinal plant produces numerous bioactive substances, including triterpene saponins of the ginsenoside-type. The endogenous levels of all types of ginsenosides largely determine the therapeutic quality of P. ginseng. Here, a field investigation was conducted to compare the changes in ginsenoside composition and mRNA expression levels of some key genes in the biosynthetic pathway of P. ginseng seedlings cultivated for different times (1, 2, 3 or 4 years). After establishing a high performance liquid chromatography method to simultaneously determine nine different ginsenosides, we measured the variations of ginsenoside contents in P. ginseng seedlings collected from our field base in Jilin province, China. The levels of total ginsenosides obviously increased with longer cultivation times and reached peak values in the 4-year seedlings. In light of the changes of ginsenosides composition, protopanaxatriol (PPT)-type ginsenosides displayed a synchronized change with total ones, while the peak point of protopanaxadiol (PPD)-type ginsenoside contents appeared in the 3-year plants. Transcript analyses of squalene synthase (SS), squalene epoxidase (SQE1) and dammarenediol synthase (DS), which are the rate-limiting enzymes in the ginsenoside biosynthetic pathway, showed that the gene expression levels of PgSS and PgSQE1 were highest in the 2-year seedlings, and could indirectly control saponins. While the PgDS gene was highly expressed in 4-year plants, and another important gene pleiotropic drug resistance (PgPDR) has a consistent trend. The further correlation analysis between gene expressions and metabolic changes showed that PgDS transcript level significantly correlated with PPT-type ginsenosides, Rg1, Re, and Rf. PgPDR expression levels positively correlated with total ginsenoside, Rg1, Re, and Rb1 (p < 0.01) and Rg3 negatively correlated with PgDS and PgPDR genes expression (p < 0.01). However, the PgSS gene expression was negatively correlated with Rb1 (p < 0.05). In conclusion, we propose that PPT-type ginsenoside and PPD or dammarenediol-II compounds have a close relationship. Particularly, we highlight recent reports on functional characterization of key genes dedicated to the production of ginsenosides in P. ginseng seedling with cultivated time.