Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
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Quinetides: diverse posttranslational modified peptides of ribonuclease-like storage protein from Panax quinquefolius as markers for differentiating ginseng species

  • Zhao, Qiang (KeyLaboratory of Structure-Based Drug Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University) ;
  • Bai, Yunpeng (CAS Key Laboratory of Separation Sciences for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences) ;
  • Liu, Dan (CAS Key Laboratory of Separation Sciences for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences) ;
  • Zhao, Nan (CAS Key Laboratory of Separation Sciences for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences) ;
  • Gao, Huiyuan (KeyLaboratory of Structure-Based Drug Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University) ;
  • Zhang, Xiaozhe (CAS Key Laboratory of Separation Sciences for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences)
  • Received : 2018.11.15
  • Accepted : 2019.05.23
  • Published : 2020.09.15
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Abstract

Background: Peptides have diverse and important physiological roles in plants and are ideal markers for species identification. It is unclear whether there are specific peptides in Panax quinquefolius L. (PQ). The aims of this study were to identify Quinetides, a series of diverse posttranslational modified native peptides of the ribonuclease-like storage protein (ginseng major protein), from PQ to explore novel peptide markers and develop a new method to distinguish PQ from Panax ginseng. Methods: We used different fragmentation modes in the LTQ Orbitrap analysis to identify the enriched Quinetide targets of PQ, and we discovered Quinetide markers of PQ and P. ginseng using ultrahigh-performance liquid chromatography-quadrupole time-of-flight mass spectrometry analysis. These "peptide markers" were validated by simultaneously monitoring Rf and F11 as standard ginsenosides. Results: We discovered 100 Quinetides of PQ with various post-translational modifications (PTMs), including a series of glycopeptides, all of which originated from the protein ginseng major protein. We effectively distinguished PQ from P. ginseng using new "peptide markers." Four unique peptides (Quinetides TP6 and TP7 as markers of PQ and Quinetides TP8 and TP9 as markers of P. ginseng) and their associated glycosylation products were discovered in PQ and P. ginseng. Conclusion: We provide specific information on PQ peptides and propose the clinical application of peptide markers to distinguish PQ from P. ginseng.

Keywords

References

  1. Vuksan V, Sievenpiper JL, Koo VY, Francis T, Beljan-Zdravkovic U, Xu Z, Vidgen E. American ginseng (Panax quinquefolius L) reduces postprandial glycemia in nondiabetic subjects and subjects with type 2 diabetes mellitus. Arch Intern Med 2000;160:1009-13. https://doi.org/10.1001/archinte.160.7.1009
  2. Qi B, Wang S, Wang Q, Zhang H, Bai XY, He HN, Sun WJ, Liu L, Zhao DQ. Characterization and immunostimulating effects on murine peritoneal macrophages of a novel protein isolated from Panax quinquefolius L. J Ethnopharmacol 2016;193:700-5. https://doi.org/10.1016/j.jep.2016.10.034
  3. Lum JH-K, Fung K-L, Cheung P-Y, Wong M-S, Lee C-H, Kwok FS-L, Leung MC-P, Hui P-K, Lo SC-L. Proteome of Oriental ginseng Panax ginseng C. A. Meyer and the potential to use it as an identification tool. Proteomics 2002;2:1123-30. https://doi.org/10.1002/1615-9861(200209)2:9<1123::AID-PROT1123>3.0.CO;2-S
  4. Yang W, Qiao X, Li K, Fan J, Bo T, Guo DA, Ye M. Identification and differentiation of Panax ginseng, Panax quinquefolium, and Panax notoginseng by monitoring multiple diagnostic chemical markers. Acta Pharm Sin B 2016;6:568-75. https://doi.org/10.1016/j.apsb.2016.05.005
  5. Zhu W, Han B, Sun Y, Wang Z, Yang X. Immunoregulatory effects of a glucogalactan from the root of Panax quinquefolium L. Carbohydr Polym 2012;87:2725-9. https://doi.org/10.1016/j.carbpol.2011.11.066
  6. Zhang K, Wang X, Ding L, Li J, Qu C-l, Chen L-g, Jin H-y, Zhang H-q. Determination of seven major ginsenosides in different parts of Panax quinquefolius L. (American ginseng) with different ages. Chem Res Chin Univ. 2008;24:707-11. https://doi.org/10.1016/S1005-9040(09)60011-8
  7. Qu C, Bai Y, Jin X, Wang Y, Zhang K, You J, Zhang H. Study on ginsenosides in different parts and ages of Panax quinquefolius L. Food Chem 2009;115:340-6. https://doi.org/10.1016/j.foodchem.2008.11.079
  8. Wang CZ, Xie JT, Fishbein A, Aung HH, He H, Mehendale SR, He TC, Du W, Yuan CS. Antiproliferative effects of different plant parts of Panax notoginseng on SW480 human colorectal cancer cells. Phytother Res: PTR 2009;23:6-13. https://doi.org/10.1002/ptr.2383
  9. Qiu S, Yang WZ, Shi XJ, Yao CL, Yang M, Liu X, Jiang BH, Wu WY, Guo DA. A green protocol for efficient discovery of novel natural compounds: characterization of new ginsenosides from the stems and leaves of Panax ginseng as a case study. Analytica Chim Acta 2015;893:65-76. https://doi.org/10.1016/j.aca.2015.08.048
  10. Li K-k, Yang X-w. Research progress of chemical components of stems and leaves of Panax ginseng. Zhongguo Xiandai Zhongyao 2012;14:47-50.
  11. Nam MH, Kim SI, Liu JR, Yang DC, Lim YP, Kwon KH, Yoo JS, Park YM. Proteomic analysis of Korean ginseng (Panax ginseng C.A. Meyer). J. Chromatogr B, Anal Technol Biomed Life Sci 2005;815:147-55. https://doi.org/10.1016/j.jchromb.2004.10.063
  12. Kim SI, Kim JY, Kim EA, Kwon KH, Kim KW, Cho K, Lee JH, Nam MH, Yang DC, Yoo JS, et al. Proteome analysis of hairy root from Panax ginseng C.A. Meyer using peptide fingerprinting, internal sequencing and expressed sequence tag data. Proteomics 2003;3:2379-92. https://doi.org/10.1002/pmic.200300619
  13. Sun H, Liu F, Sun L, Liu J, Wang M, Chen X, Xu X, Ma R, Feng K, Jiang R. Proteomic analysis of amino acid metabolism differences between wild and cultivated Panax ginseng. J Ginseng Res 2016;40:113-20. https://doi.org/10.1016/j.jgr.2015.06.001
  14. Liu S, Wang S, Liu M, Yang F, Zhang H, Liu S, Wang Q, Zhao Y. De novo sequencing and analysis of the transcriptome of Panax ginseng in the leafexpansion period. Mol Med Rep 2016;14:1404-12. https://doi.org/10.3892/mmr.2016.5376
  15. Liwei S. Two-dimensional gel electrophoresis analysis of different parts of Panax quinquefolius L. root. Afr J Biotechnol 2011;10.
  16. Yoon JY, Ha BH, Woo JS, Lim YH, Kim KH. Purification and characterization of a 28-kDa major protein from ginseng root. Comp. Biochem. Physiol., Part B: Biochem. Mol. Biol. 2002;132B:551-7.
  17. Kim SI, Kweon SM, Kim EA, Kim JY, Kim S, Yoo JS, Park YM. Characterization of RNase-like major storage protein from the ginseng root by proteomic approach. J Plant Physiol 2004;161:837-45. https://doi.org/10.1016/j.jplph.2004.01.001
  18. Kwon TH, Oh SR, Park H, Kim KH. Purification of a major protein with physiological activities from Panax ginseng C.A. Meyer. Han'guk Nonghwa Hakhoechi 1998;41:410-3.
  19. Sun Tae Kim D-WB, Lee Kyunghee, Hwang Jung Eun, Bang Kyong-Hwan. Proteomic analysis of Korean ginseng (Panax ginseng C. A.Meyer ) following exposure to salt stress. 2008.
  20. Jahn H, Wittke S, Zurbig P, Raedler TJ, Arlt S, Kellmann M, Mullen W, Eichenlaub M, Mischak H, Wiedemann K. Peptide fingerprinting of Alzheimer's disease in cerebrospinal fluid: identification and prospective evaluation of new synaptic biomarkers. PLoS One 2011;6:12.
  21. Hui L, Cunningham R, Zhang Z, Cao W, Jia C, Li L. Discovery and characterization of the Crustacean hyperglycemic hormone precursor related peptides (CPRP) and orcokinin neuropeptides in the sinus glands of the blue crab Callinectes sapidus using multiple tandem mass spectrometry techniques. J Proteome Res 2011;10:4219-29. https://doi.org/10.1021/pr200391g
  22. Ye X, Zhao N, Yu X, Han X, Gao H, Zhang X. Extensive characterization of peptides from Panax ginseng C. A. Meyer using mass spectrometric approach. Proteomics 2016;16:2788-91. https://doi.org/10.1002/pmic.201600183
  23. Marmiroli N, Maestri E. Plant peptides in defense and signaling. Peptides (N. Y., NY, U. S.) 2014;56:30-44. https://doi.org/10.1016/j.peptides.2014.03.013
  24. Zhan C, Li S, Zhong Q, Zhou D. Structure-based grafting, mutation, and optimization of peptide inhibitors to fit in the active pocket of human secreted phospholipase A2: find new use of old Peptide agents with anti-inflammatory activity. Chem Biol Drug Des 2015;85:418-26. https://doi.org/10.1111/cbdd.12424
  25. Chavan SG, Deobagkar DD. An in silico insight into novel therapeutic interaction of LTNF peptide-LT10 and design of structure based peptidomimetics for putative anti-diabetic activity. PLoS One 2015;10:e0121860. https://doi.org/10.1371/journal.pone.0121860
  26. Chen CF, Chiou WF, Zhang JT. Comparison of the pharmacological effects of Panax ginseng and Panax quinquefolium. Acta Pharmacol Sin 2008;29:1103-8. https://doi.org/10.1111/j.1745-7254.2008.00868.x
  27. Li L, Luo GA, Liang QL, Hu P, Wang YM. Rapid qualitative and quantitative analyses of Asian ginseng in adulterated American ginseng preparations by UPLC/Q-TOF-MS. J Pharm Biomed Anal 2010;52:66-72. https://doi.org/10.1016/j.jpba.2009.12.017
  28. Lee TM, Marderosian AD. Two-Dimensional TLC analysis of ginsenosides from root of dwarf ginseng (Panax trifolius L.) Araliaceae. J Pharmaceut Sci 1981;70:89-91. https://doi.org/10.1002/jps.2600700119
  29. Fuzzati N, Gabetta B, Jayakar K, Pace R, Peterlongo F. Liquid chromatographyelectrospray mass spectrometric identification of ginsenosides in Panax ginseng roots. J Chromatogr A 1999;854:69-79. https://doi.org/10.1016/S0021-9673(99)00463-X
  30. Li W, Gu C, Zhang H, Awang DVC, Fitzloff JF, Fong HHS, van Breemen RB. Use of high-performance liquid chromatography-tandem mass spectrometry to distinguish Panax ginseng C. A. Meyer (Asian ginseng) and Panax quinquefolius L. (North American ginseng). Anal Chem. 2000;72:5417-22. https://doi.org/10.1021/ac000650l
  31. Li W, Gu C, Zhang H, Awang DVC, Fitzloff JF, Fong HHS, van Breemen RB. Use of high-performance liquid ChromatographyTandem mass spectrometry to distinguish Panax ginseng C. A. Meyer (Asian ginseng) and Panax quinquefolius L. (North American ginseng). Anal Chem 2000;72:5417-22. https://doi.org/10.1021/ac000650l
  32. Puntmann VO. How-to guide on biomarkers: biomarker definitions, validation and applications with examples from cardiovascular disease. Postgrad Med J 2009;85:538-45. https://doi.org/10.1136/pgmj.2008.073759
  33. Pepe MS, Thompson ML. Combining diagnostic test results to increase accuracy. Biostatistics 2000;1:123-40. https://doi.org/10.1093/biostatistics/1.2.123
  34. Zhao Q, Zhao N, Ye X, He M, Yang Y, Gao H, Zhang X. Rapid discrimination between red and white ginseng based on unique mass-spectrometric features. J Pharm Biomed Anal 2019;164:202-10. https://doi.org/10.1016/j.jpba.2018.10.007
  35. Gelman JS, Sironi J, Castro LM, Ferro ES, Fricker LD. Peptidomic analysis of human cell lines. J Proteome Res 2011;10:1583-92. https://doi.org/10.1021/pr100952f
  36. Bai Y, Zhao Q, He M, Ye X, Zhang X. Extensive characterization and differential analysis of endogenous peptides from Bombyx batryticatus using mass spectrometric approach. J Pharm Biomed Anal 2018;163:78-87. https://doi.org/10.1016/j.jpba.2018.09.033
  37. Qian MG, Zhang Y, Lubman DM. Collision-induced dissociation of multiply charged peptides in an ion-trap storage/reflectron time-of-flight mass spectrometer. Rapid Commun Mass Spectrom 1995;9:1275-82. https://doi.org/10.1002/rcm.1290091311
  38. Levery SB, Steentoft C, Halim A, Narimatsu Y, Clausen H, Vakhrushev SY. Advances in mass spectrometry driven O-glycoproteomics. Biochim Biophys Acta 2015;1850:33-42. https://doi.org/10.1016/j.bbagen.2014.09.026
  39. Pasing Y, Sickmann A, Lewandrowski U. N-glycoproteomics:mass spectrometrybased glycosylation site annotation. Biol Chem 2012;393:249-58. https://doi.org/10.1515/hsz-2011-0245
  40. Wang HX, Ng TB. Quinqueginsin, a novel protein with anti-human immunodeficiency virus, antifungal, ribonuclease and cell-free translation-inhibitory activities from American ginseng roots. Biochem Biophys Res Commun 2000;269:203-8. https://doi.org/10.1006/bbrc.2000.2114
  41. Ng TB, Wang H. Panaxagin, a new protein from Chinese ginseng possesses anti-fungal, anti-viral, translation-inhibiting and ribonuclease activities. Life Sci 2001;68:739-49. https://doi.org/10.1016/S0024-3205(00)00970-X
  42. Lam SK, Ng TB. Isolation of a novel thermolabile heterodimeric ribonuclease with antifungal and Antiproliferative activities from roots of the sanchi ginseng Panax notoginseng. Biochem Biophys Res Commun 2001;285:419-23. https://doi.org/10.1006/bbrc.2001.5193
  43. Wang HX, Ng TB. A ribonuclease from Chinese ginseng (Panax ginseng) flowers. Protein Expr Purif 2004;33:195-9. https://doi.org/10.1016/j.pep.2003.09.002
  44. Wang HX, Ng TB. Isolation of a ribonuclease from sanchi ginseng (Panax pseudoginseng) flowers distinct from other ginseng ribonucleases. Biochem Biophys Res Commun 2006;343:198-202. https://doi.org/10.1016/j.bbrc.2006.02.130
  45. Choi SH, Hong MK, Kim HJ, Ryoo N, Rhim H, Nah SY, Kang LW. Structure of ginseng major latex-like protein 151 and its proposed lysophosphatidic acidbinding mechanism. Acta Crystallogr D Biol Crystallogr 2015;71:1039-50. https://doi.org/10.1107/S139900471500259X
  46. Choi S-H, Kim H-J, Cho H-J, Park S-D, Lee N-E, Hwang S-H, Cho I-H, Hwang H, Rhim H, Kim H-C, et al. Gintonin, a ginseng-derived exogenous lysophosphatidic acid receptor ligand, protects Astrocytes from hypoxic and Reoxygenation stresses through stimulation of Astrocytic glycogenolysis. Mol Neurobiol 2018.
  47. Ohtsubo K, Marth JD. Glycosylation in cellular mechanisms of health and disease. Cell 2006;126:855-67. https://doi.org/10.1016/j.cell.2006.08.019
  48. Luo H, Zhu D, Wang Y, Chen Y, Jiang R, Yu P, Qiu Z. Study on the structure of ginseng glycopeptides with anti-inflammatory and Analgesic activity. Molecules 2018;23.

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