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

Xuanming Zhang; Can Kong; Xixin Wang; Hairong Hou; Hongxia Yu; Lizhen Wang; Peihai Li; Xiaobin Li; Yun Zhang; Liwen Han; Kechun Liu

doi:10.1055/a-2058-1199

Planta Medica, Table of Contents

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

¹Engineering 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

¹Engineering 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

¹Engineering 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

¹Engineering 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

³Wendeng Daodishen Industry Co. Ltd., Weihai, China

,

Lizhen Wang

¹Engineering 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

¹Engineering 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

¹Engineering 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

¹Engineering 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

¹Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening, Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan, China

²College of Pharmacy and Pharmaceutical Sciences, Shandong First Medical University (Shandong Academy of Medical Sciences), Jinan, China

,

Kechun Liu

¹Engineering 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

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

Full Text

References

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
2 Kim DH. Chemical diversity of Panax ginseng, Panax quinquifolium, and Panax notoginseng . J Ginseng Res 2012; 36: 1-15
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
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
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
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
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
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
9 Hou MQ, Wang RF, Zhao SJ, Wang ZT. Ginsenosides in Panax genus and their biosynthesis. Acta Pharm Sin B 2021; 11: 1813-1834
10 Mancuso C, Santangelo R. Panax ginseng and Panax quinquefolius: From pharmacology to toxicology. Food Chem Toxicol 2017; 107: 362-372,
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
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
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
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
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
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
17 Ma XQ, Xiao HB, Liang XM. Identification of ginsenosides in Panax quinquefolium by LC-MS. Chromatographia 2006; 64: 31-36
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
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
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
21 Ryan CT, Patel V, Rosengart TK. Clinical potential of angiogenic therapy and cellular reprogramming. JTCVS Open 2021; 6: 108-115
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
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
24 Richard DE, Vouret-Craviari V, Pouysségur J. Angiogenesis and G-protein-coupled receptors: Signals that bridge the gap. Oncogene 2001; 20: 1556-1562
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
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
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
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
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
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
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
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
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
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
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
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
37 Nakhjavani M, Smith E, Townsend AR, Price TJ, Hardingham JE. Anti-Angiogenic Properties of Ginsenoside Rg3. Molecules 2020; 25: 4905
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
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
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

Supplementary Material

Supporting Information