Download PDF
CC BY-NC-ND 4.0 · Planta Med 2023; 89(07): 764-772
DOI: 10.1055/a-2058-1199
Natural Product Chemistry & Analytical Studies
Original Papers

LC-MS Analysis of Ginsenosides in Different Parts of Panax quinquefolius and Their Potential for Coronary Disease Improvement

Xuanming Zhang 
1   Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening, Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan, China
,
Can Kong
1   Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening, Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan, China
,
Xixin Wang 
1   Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening, Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan, China
,
Hairong Hou
1   Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening, Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan, China
,
Hongxia Yu
3   Wendeng Daodishen Industry Co. Ltd., Weihai, China
,
Lizhen Wang
1   Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening, Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan, China
,
Peihai Li
1   Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening, Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan, China
,
Xiaobin Li
1   Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening, Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan, China
,
Yun Zhang
1   Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening, Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan, China
,
Liwen Han
1   Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening, Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan, China
2   College of Pharmacy and Pharmaceutical Sciences, Shandong First Medical University (Shandong Academy of Medical Sciences), Jinan, China
,
Kechun Liu
1   Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening, Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan, China
› Author Affiliations
› Further Information
   Permissions and Reprints

Abstract

Seven main ginsenosides, including ginsenoside Re, ginsenoside Rb1, pseudoginsenoside F11, ginsenoside Rb2, ginsenoside Rb3, ginsenoside Rd, and ginsenoside F2, were identified by LC-QTOF MS/MS from root, leaf and flower extracts of Panax quinquefolius. These extracts promoted intersegmental vessel growth in a zebrafish model, indicating their potential cardiovascular health benefits. Network pharmacology analysis was then conducted to reveal the potential mechanisms of ginsenoside activity in the treatment of coronary artery disease. GO and KEGG enrichment analyses elucidated that G protein-coupled receptors played a critical role in VEGF-mediated signal transduction and that the molecular pathways associated with ginsenoside activity are involved in neuroactive ligand–receptor interaction, cholesterol metabolism, the cGMP–PKG signaling pathway, etc. Moreover, VEGF, FGF2, and STAT3 were confirmed as the major targets inducing proliferation of endothelial cells and driving the pro-angiogenic process. Overall, ginsenosides could be potent nutraceutical agents that act to reduce the risks of cardiovascular disease. Our findings will provide a basis to utilize the whole P. quinquefolius plant in drugs and functional foods.

Key words

Ginsenoside - Danio rerio - coronary artery disease - network pharmacology - Panax quinquefolius - Araliaceae

Supporting Information

    Supplementary Figure 1S–8S: MS and MS/MS spectra of ginsenoside Re in negative mode; MS and MS/MS spectra of ginsenoside Rb1 in negative mode; MS and MS/MS spectra of pseudoginsenoside F11 in negative mode; MS and MS/MS spectra of ginsenoside Rb2 in negative mode; MS and MS/MS spectra of ginsenoside Rb3 in negative mode; MS and MS/MS spectra of ginsenoside Rd in negative mode; MS and MS/MS spectra of ginsenoside F2 in negative mode; Chemical structures of the identified ginsenosides.

    Supplementary Tables 1S–3S: Retention time and characteristic ions of the ginsenosides evaluated using LC-MS/MS analysis; Angiogenic Activities in Zebrafish Larvae; The general network properties of the major targets.

  • Supporting Information


Publication History

Received: 26 September 2022

Accepted after revision: 12 March 2023

Accepted Manuscript online:
20 March 2023

Article published online:
17 April 2023

© 2022. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Jee HS, Chang KH, Park SH, Kim KT, Paik HD. Morphological characterization, chemical components, and biofunctional activities of Panax ginseng, Panax quinquefolium, and Panax notoginseng roots: A comparative study. Food Reviews International 2014; 30: 91-111
    CrossrefPubMedGoogle Scholar
  • 2 Kim DH. Chemical diversity of Panax ginseng, Panax quinquifolium, and Panax notoginseng . J Ginseng Res 2012; 36: 1-15
    CrossrefPubMedGoogle Scholar
  • 3 Liu H, Burkhart EP, Chen VYJ, Wei X. Promotion of in situ forest farmed American ginseng (Panax quinquefolius L.) as a sustainable use strategy: Opportunities and challenges. Frontiers in Ecology and Evolution 2021; 9: 652103
    CrossrefPubMedGoogle Scholar
  • 4 Zhang XM, Lu XH, Jiao XL, Bi YM, Gao WW. First report of Ilyonectria vredehoekensis causing rusty root on American ginseng in China. Plant Dis 2019; 103: 2944
    CrossrefPubMedGoogle Scholar
  • 5 Du ZX, Li JH, Zhang X, Pei J, Huang LF. An integrated LC-MS-based strategy for the quality assessment and discrimination of three Panax species. Molecules 2018; 23: 2988
    CrossrefPubMedGoogle Scholar
  • 6 Yang WZ, Qiao X, Li K, Fan JR, 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: 568-575
    CrossrefPubMedGoogle Scholar
  • 7 Yang WZ, Shi XJ, Yao CL, Huang Y, Hou JJ, Han SM, Feng ZJ, Wei WL, Wu WY, Guo DA. A novel neutral loss/product ion scan-incorporated integral approach for the untargeted characterization and comparison of the carboxyl-free ginsenosides from Panax ginseng, Panax quinquefolius, and Panax notoginseng . J Pharm Biomed Anal 2020; 177: 112813
    CrossrefPubMedGoogle Scholar
  • 8 Shi XJ, Yang WZ, Qiu S, Yao CL, Shen Y, Pan HQ, Bi QR, Yang M, Wu WY, Guo DA. An in-source multiple collision-neutral loss filtering based nontargeted metabolomics approach for the comprehensive analysis of malonyl-ginsenosides from Panax ginseng, P. quinquefolius, and P. notoginseng . Anal Chim Acta 2017; 952: 59-70
    CrossrefPubMedGoogle Scholar
  • 9 Hou MQ, Wang RF, Zhao SJ, Wang ZT. Ginsenosides in Panax genus and their biosynthesis. Acta Pharm Sin B 2021; 11: 1813-1834
    CrossrefPubMedGoogle Scholar
  • 10 Mancuso C, Santangelo R. Panax ginseng and Panax quinquefolius: From pharmacology to toxicology. Food Chem Toxicol 2017; 107: 362-372,
    CrossrefPubMedGoogle Scholar
  • 11 Yuan CS, Wang CZ, Wicks SM, Qi LW. Chemical and pharmacological studies of saponins with a focus on American ginseng. J Ginseng Res 2010; 34: 160-167
    CrossrefPubMedGoogle Scholar
  • 12 Ratan ZA, Haidere MF, Hong YH, Park SH, Lee JO, Lee JS, Cho JY. Pharmacological potential of ginseng and its major component ginsenosides. J Ginseng Res 2021; 45: 199-210
    CrossrefPubMedGoogle Scholar
  • 13 Ma ZN, Li YZ, Li W, Yan XT, Yang G, Zhang J, Zhao LC, Yang LM. Nephroprotective effects of saponins from leaves of Panax quinquefolius against cisplatin-induced acute kidney injury. Int J Mol Sci 2017; 18: 1407
    CrossrefPubMedGoogle Scholar
  • 14 Li F, Lv CN, Li Q, Wang J, Song D, Liu PP, Zhang DD, Lu JC. Chemical and bioactive comparison of flowers of Panax ginseng Meyer, Panax quinquefolius L., and Panax notoginseng Burk. J Ginseng Res 2017; 41: 487-495
    CrossrefPubMedGoogle Scholar
  • 15 Wang HD, Zhang CX, Zuo TT, Li WW, Jia L, Wang XY, Qian YX, Guo D, Yang WZ. In-depth profiling, characterization, and comparison of the ginsenosides among three different parts (the root, stem leaf, and flower bud) of Panax quinquefolius L. by ultra-high performance liquid chromatography/quadrupole-Orbitrap mass spectrometry. Anal Bioanal Chem 2019; 411: 7817-7829
    CrossrefPubMedGoogle Scholar
  • 16 Li SL, Lai SF, Song JZ, Qiao CF, Liu X, Zhou Y, Cai H, Cai BC, Xu HX. Decocting-induced chemical transformations and global quality of Du-Shen-Tang, the decoction of ginseng evaluated by UPLC-Q-TOF-MS/MS based chemical profiling approach. J Pharm Biomed Anal 2010; 53: 946-957
    CrossrefPubMedGoogle Scholar
  • 17 Ma XQ, Xiao HB, Liang XM. Identification of ginsenosides in Panax quinquefolium by LC-MS. Chromatographia 2006; 64: 31-36
    CrossrefPubMedGoogle Scholar
  • 18 Mao Q, Bai M, Xu JD, Kong M, Zhu LY, Zhu H, Wang Q, Li SL. Discrimination of leaves of Panax ginseng and P. quinquefolius by ultra high performance liquid chromatography quadrupole/time-of-flight mass spectrometry based metabolomics approach. J Pharm Biomed Anal 2014; 97: 129-140
    CrossrefPubMedGoogle Scholar
  • 19 Wang J, Liu H, Gao WY, Zhang LM. Comparison of ginsenoside composition in native roots and cultured callus cells of Panax quinquefoliumL . Acta Physiol Plant 2013; 35: 1363-1366
    CrossrefPubMedGoogle Scholar
  • 20 Malakar AK, Choudhury D, Halder B, Paul P, Uddin A, Chakraborty S. A review on coronary artery disease, its risk factors, and therapeutics. J Cell Physiol 2019; 234: 16812-16823
    CrossrefPubMedGoogle Scholar
  • 21 Ryan CT, Patel V, Rosengart TK. Clinical potential of angiogenic therapy and cellular reprogramming. JTCVS Open 2021; 6: 108-115
    CrossrefPubMedGoogle Scholar
  • 22 Zhang XM, Shi YP, Wang LZ, Li XB, Zhang SS, Wang XM, Jin M, Hsiao CD, Lin HW, Han LW, Liu KC. Metabolomics for biomarker discovery in fermented black garlic and potential bioprotective responses against cardiovascular diseases. J Agric Food Chem 2019; 44: 12191-12198
    CrossrefPubMedGoogle Scholar
  • 23 Wang X, Wang ZY, Zheng JH, Li S. TCM network pharmacology: A new trend towards combining computational, experimental and clinical approaches. Chin J Nat Med 2021; 19: 1-11
    PubMedGoogle Scholar
  • 24 Richard DE, Vouret-Craviari V, Pouysségur J. Angiogenesis and G-protein-coupled receptors: Signals that bridge the gap. Oncogene 2001; 20: 1556-1562
    CrossrefPubMedGoogle Scholar
  • 25 Zhang XD, Liu LG, Liu DY, Li YT, He J, Shen L. 17β-Estradiol promotes angiogenesis of bone marrow mesenchymal stem cells by upregulating the PI3K-Akt signaling pathway. Comput Struct Biotechnol J 2022; 20: 3864-3873
    CrossrefPubMedGoogle Scholar
  • 26 Latifi-Navid H, Soheili ZS, Samiei S, Sadeghi M, Taghizadeh S, Pirmardan ER, Ahmadieh H. Network analysis and the impact of Aflibercept on specific mediators of angiogenesis in HUVEC cells. J Cell Mol Med 2021; 25: 8285-8299
    CrossrefPubMedGoogle Scholar
  • 27 Lam HW, Lin HC, Lao SC, Gao JL, Hong SJ, Leong CW, Yue PYK, Kwan YW, Leung AYH, Wang YT, Lee SMY. The angiogenic effects of Angelica sinensis extract on HUVEC in vitro and zebrafish in vivo. J Cell Biochem 2008; 103: 195-211
    CrossrefPubMedGoogle Scholar
  • 28 Jiang M, Murias JM, Chrones T, Sims SM, Lui E, Noble EG. American ginseng acutely regulates contractile function of rat heart. Front Pharmacol 2014; 5: 43
    CrossrefPubMedGoogle Scholar
  • 29 Kim JH. Pharmacological and medical applications of Panax ginseng and ginsenosides: a review for use in cardiovascular diseases. J Ginseng Res 2018; 42: 264-269
    CrossrefPubMedGoogle Scholar
  • 30 Yao QY, Huang YQ, Liu AD, Zhu MZ, Liu J, Yan H, Zhang QY, Geng B, Gao YS, Du SX, Huang P, Tang CS, Du JB, Jin HF. The vasodilatory effect of sulfur dioxide via SGC/cGMP/PKG pathway in association with sulfhydryl-dependent dimerization. Am J Physiol Regul Integr Comp Physiol 2016; 310: R1073-R1080
    CrossrefPubMedGoogle Scholar
  • 31 Zhang K, Song W, Li DL, Jin X. Apigenin in the regulation of cholesterol metabolism and protection of blood vessels. Exp Ther Med 2017; 13: 1719-1724
    CrossrefPubMedGoogle Scholar
  • 32 Liu J, Wang XD, Lin JH, Li SH, Deng GX, Wei JR. Classifiers for predicting coronary artery disease based on gene expression profiles in peripheral blood mononuclear cells. Int J Gen Med 2021; 14: 5651-5663
    CrossrefPubMedGoogle Scholar
  • 33 Yoodee S, Peerapen P, Plumworasawat S, Thongboonkerd V. ARID1A knockdown in human endothelial cells directly induces angiogenesis by regulating angiopoietin-2 secretion and endothelial cell activity. Int J Biol Macromol 2021; 180: 1-13
    CrossrefPubMedGoogle Scholar
  • 34 Pulkkinen HH, Kiema M, Lappalainen JP, Toropainen A, Beter M, Tirronen A, Holappa L, Niskanen H, Kaikkonen MU, Ylä-Herttuala S, Laakkonen JP. BMP6/TAZ-Hippo signaling modulates angiogenesis and endothelial cell response to VEGF. Angiogenesis 2021; 24: 129-144
    CrossrefPubMedGoogle Scholar
  • 35 Chen SH, Murphy D, Lassoued W, Thurston G, Feldman MD, Lee WMF. Activated STAT3 is a mediator and biomarker of VEGF endothelial activation. Cancer Biol Ther 2008; 7: 1994-2003
    CrossrefPubMedGoogle Scholar
  • 36 Yang X, Qiao D, Meyer K, Friedl A. Signal transducers and activators of transcription mediate fibroblast growth hactor-induced vascular endothelial morphogenesis. Cancer Res 2009; 69: 1668-1677
    CrossrefPubMedGoogle Scholar
  • 37 Nakhjavani M, Smith E, Townsend AR, Price TJ, Hardingham JE. Anti-Angiogenic Properties of Ginsenoside Rg3. Molecules 2020; 25: 4905
    CrossrefPubMedGoogle Scholar
  • 38 Yue PYK, Wong DYL, Wu PK, Leung PY, Mak NK, Yeung HW, Liu L, Cai ZW, Jiang ZH, Fan TPD, Wong RNS. The angiosuppressive effects of 20(R)-ginsenoside Rg3. Biochem Pharmacol 2006; 72: 437-445
    CrossrefPubMedGoogle Scholar
  • 39 Che YH, Xu ZR, Ni LL, Dong XX, Yang ZZ, Yang ZB. Isolation and identification of the components in Cybister chinensis Motschulsky against inflammation and their mechanisms of action based on network pharmacology and molecular docking. J Ethnopharmacol 2022; 285: 114851
    CrossrefPubMedGoogle Scholar
  • 40 Shi L, Yang F, Luo F, Liu Y, Zhang F, Zou MJ, Liu QZ. Evodiamine exerts anti-tumor effects against hepatocellular carcinoma through inhibiting β-catenin-mediated angiogenesis. Tumor Biol 2016; 37: 12791-12803
    CrossrefPubMedGoogle Scholar