Metabolomics Based Comparison on the Biomarkers between Panax Notoginseng and its Counterfeit Gynura Segetum in Rats

Author(s): Yin Zhang, Haixia Zhang, Jianfeng Shi, Shoubei Qiu, Qianqian Fei, Fenxia Zhu, Jing Wang, Yiping Huang, Daoquan Tang, Bin Chen*

Journal Name: Current Pharmaceutical Analysis

Volume 16 , Issue 8 , 2020


Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


Abstract:

Background: Because of the similar appearance of Gynura segetum and panax notoginseng, the patients often mistakenly use Gynura segetum as Panax notoginseng, which causes serious liver damage. There is no comparative study on the metabolism of Gynura segetum and Panax notoginseng in the literature. This study was conducted to compare the difference between Panax notoginseng and its counterfeit Gynura segetum by using metabolomics method.

Methods: In this paper, an ultra performance liquid chromatography coupled to quadrupole time-offlight mass spectrometric(UPLC-Q/TOF/MS) were used to detect the type of endogenous metabolites in urine and plasma of three groups (normal group, ethanol extract of panax notoginseng, decoction of Gynura segetum respectively, and different multivariate statistical analysis methods were established.

Results: In this experiment, main urine biomarkers were L-glutamate, L-methionine, cytidine, and Ltyrosine in the Panax notoginseng group, which are phytosphingosine, creatine and sphinganine in the Gynura segetum group. The plasma biomarkers identified in the Panax notoginseng group were arachidonic acid, L-tyrosine, linoleic acid, alpha-linolenoyl ethanolamide and lysoPC (15:0), and in the Gynura segetum group are L-arginine, L-valine, arachidonic acid and LysoPC(18:2(9Z,12Z)).

Conclusion: There are significant difference between Panax notoginseng and Gynura segetum in biomarkers from the perspective of metabolomics in the body.

Keywords: UPLC-Q/TOF/MS, metabolomics, panax notoginseng, Gynura segetum, biomarker, pathway analysis.

[1]
Duan, L.; Xiong, X.; Hu, J.; Liu, Y.; Li, J.; Wang, J. Panax notoginseng Saponins for treating coronary artery disease: a functional and mechanistic overview. Front. Pharmacol., 2017, 8, 702.
[http://dx.doi.org/10.3389/fphar.2017.00702] [PMID: 29089889]
[2]
Song, H.; Wang, P.; Liu, J.; Wang, C. panax notoginseng preparations for unstable angina pectoris: a systematic review and meta-analysis. Phytother. Res., 2017, 31(8), 1162-1172.
[http://dx.doi.org/10.1002/ptr.5848] [PMID: 28634988]
[3]
Xie, W.; Meng, X.; Zhai, Y.; Zhou, P.; Ye, T.; Wang, Z.; Sun, G.; Sun, X. Panax notoginseng saponins: a review of its mechanisms of antidepressant or anxiolytic effects and network analysis on phytochemistry and pharmacology. Molecules, 2018, 23(4), 940.
[http://dx.doi.org/10.3390/molecules23040940] [PMID: 29673237]
[4]
Chan, E.C.Y.; Yap, S.L.; Lau, A.J.; Leow, P.C.; Toh, D.F.; Koh, H.L. Ultra-performance liquid chromatography/time-of-flight mass spectrometry based metabolomics of raw and steamed Panax notoginseng. Rapid Commun. Mass Spectrom., 2007, 21(4), 519-528.
[http://dx.doi.org/10.1002/rcm.2864] [PMID: 17238214]
[5]
Gao, H.; Li, N.; Wang, J.Y.; Zhang, S.C.; Lin, G. Definitive diagnosis of hepatic sinusoidal obstruction syndrome induced by pyrrolizidine alkaloids. J. Dig. Dis., 2012, 13(1), 33-39.
[http://dx.doi.org/10.1111/j.1751-2980.2011.00552.x] [PMID: 22188914]
[6]
Lin, G.; Wang, J.Y.; Li, N.; Li, M.; Gao, H.; Ji, Y.; Zhang, F.; Wang, H.; Zhou, Y.; Ye, Y.; Xu, H.X.; Zheng, J. Hepatic sinusoidal obstruction syndrome associated with consumption of Gynura segetum. J. Hepatol., 2011, 54(4), 666-673.
[http://dx.doi.org/10.1016/j.jhep.2010.07.031] [PMID: 21146894]
[7]
Chen, Q.; Liang, Z.; Brand, E.; Chen, H.; Zhao, Z. Distributive and Quantitative analysis of the main active saponins in panax notoginseng by uhplc-qtof/ms combining with fluorescence microscopy and laser microdissection. Planta Med., 2016, 82(3), 263-272.
[http://dx.doi.org/10.1055/s-0035-1558311] [PMID: 26824619]
[8]
Richardson, P.; Guinan, E. The pathology, diagnosis, and treatment of hepatic veno-occlusive disease: current status and novel approaches. Br. J. Haematol., 1999, 107(3), 485-493.
[http://dx.doi.org/10.1046/j.1365-2141.1999.01680.x] [PMID: 10583247]
[9]
Song, Q.; Zhang, A.; Yan, G.; Zhang, A.H.; Yan, G.L.; Liu, L.; Wang, X.J. Technological advances in current metabolomics and its application in tradition Chinese medicine. RSC Advances, 2017, 7(84), 53516-53524.
[http://dx.doi.org/10.1039/C7RA02056B]
[10]
Liu, C.X. Metabolomics studies contribute to the understanding of complex systems and the overall effect of traditional Chinese medicine. Chin. J. Nat. Med., 2009, (2), 81-81.
[http://dx.doi.org/10.3724/SP.J.1009.2009.00081]
[11]
Hu, C.; Xu, G. Metabolomics and traditional Chinese medicine. Trends Analyt. Chem., 2014, 61(1), 207-214.
[http://dx.doi.org/10.1016/j.trac.2014.06.007]
[12]
Wang, M.; Chen, L.; Liu, D.; Chen, H.; Tang, D.D.; Zhao, Y.Y. Metabolomics highlights pharmacological bioactivity and biochemical mechanism of traditional Chinese medicine. Chem. Biol. Interact., 2017, 273, 133-141.
[http://dx.doi.org/10.1016/j.cbi.2017.06.011] [PMID: 28619388]
[13]
Yan, Y.; Zhang, A.; Dong, H.; Yan, G.; Sun, H.; Wu, X.; Han, Y.; Wang, X. Toxicity and detoxification effects of herbal caowu via ultra performance liquid chromatography/mass spectrometry metabolomics analyzed using pattern recognition method. Pharmacogn. Mag., 2017, 13(52), 683-692.
[http://dx.doi.org/10.4103/pm.pm_475_16] [PMID: 29200734]
[14]
Zhao, S.; Wang, PC.; Feng, J.; Chen, Z.L.; Wang, Q.H.; Kuang, H.X. Application of metabonomics in study on traditional Chinese medicine Chin. Tradit. Herb. Drugs, 2015, (5), 756-765.
[15]
Siddiqui, M.R.; Alothman, Z.A.; Rahman, N. Analytical techniques in pharmaceutical analysis: A review. Arab. J. Chem., 2013, 10, S1409-S1421.
[16]
Alothman, Z.A.; Rahman, N.; Siddiqui, M.R. Review on pharmaceutical impurities, stability studies and degradation products: An Analytical Approach. Rev. Adv. Sci. Eng., 2013, 2(2), 155-166.
[http://dx.doi.org/10.1166/rase.2013.1039]
[17]
Rahman, N.; Azmi, S.N.H.; Wu, H.F. The importance of impurity analysis in pharmaceutical products: an integrated approach. Accredit. Qual. Assur., 2006, 11(1-2), 69-74.
[http://dx.doi.org/10.1007/s00769-006-0095-y]
[18]
Meng, Z.; Shi, Z.; Su, M.; Sun, H.W. In vitro metabolism analysis of sulfamerazine in mice liver by ultra performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry. Curr. Pharm. Anal., 2018, 14(1)
[http://dx.doi.org/10.2174/1573412913666161129125740]
[19]
Guo, X.; Wang, P.; Hu, X.; Fang, L.; Zhao, P.; Jiang, Z. Pharmacokinetic study of four components in rat plasma after oral administration of guanmaitong granule by UPLC-MS/MS. Curr. Pharm. Anal., 2018, 13(999), 1-1.
[http://dx.doi.org/10.2174/1573412913666170303105121]
[20]
Papadoyannis, I.N.; Theodoridis, G.A. Novel advanced approaches in sample preparation and analyte detection for bioanalysis. Curr. Pharm. Anal., 2006, 2(4), 385-404.
[http://dx.doi.org/10.2174/157341206778699591]
[21]
Szymańska, E.; Saccenti, E.; Smilde, A.K.; Westerhuis, J.A. Double-check: validation of diagnostic statistics for PLS-DA models in metabolomics studies. Metabolomics, 2012, 8(Suppl. 1), 3-16.
[http://dx.doi.org/10.1007/s11306-011-0330-3] [PMID: 22593721]
[22]
Li, Z.; Lu, Y.; Guo, Y.; Cao, H.; Wang, Q.; Hui, W. Comprehensive evaluation of untargeted metabolomics data processing software in feature detection, quantification and discriminating marker selection. Anal. Chim. Acta, 2018, 31, 50-57.
[http://dx.doi.org/10.1016/j.aca.2018.05.001]
[23]
Triba, M.N.; Le Moyec, L.; Amathieu, R.; Goossens, C.; Bouchemal, N.; Nahon, P.; Rutledge, D.N.; Savarin, P. PLS/OPLS models in metabolomics: the impact of permutation of dataset rows on the K-fold cross-validation quality parameters. Mol. Biosyst., 2015, 11(1), 13-19.
[http://dx.doi.org/10.1039/C4MB00414K] [PMID: 25382277]
[24]
Afendi, F.M.; Ono, N.; Nakamura, Y.; Nakamura, K.; Darusman, L.K.; Kibinge, N.; Morita, A.H.; Tanaka, K.; Horai, H.; Altaf-Ul-Amin, M.; Kanaya, S. Data Mining methods for omics and knowledge of crude medicinal plants toward big data biology Comput. Struct. Bi-otechnol. J, 2013, 4e201301010.,
[http://dx.doi.org/10.5936/csbj.201301010]
[25]
Gromski, P.S.; Muhamadali, H.; Ellis, D.I.; Xu, Y.; Correa, E.; Turner, M.L.; Goodacre, R. A tutorial review: Metabolomics and partial least squares-discriminant analysis--a marriage of convenience or a shotgun wedding. Anal. Chim. Acta, 2015, 879, 10-23.
[http://dx.doi.org/10.1016/j.aca.2015.02.012] [PMID: 26002472]
[26]
Yu, C.Q.; Li, L.N. Research Advancement on Arachidonic Acid. Acad. Period. Fram. Prod. Process, 2007, 4(97), 10-12.
[27]
Yuan, C.L.; Yao, J.M.; Yu, Z.L. the biological effects of arachidonic acid and its metabolites. Zhongguo Yaowu Huaxue Zazhi, 2000, 35(10), 75-78.
[28]
Tallima, H.; El Ridi, R. Arachidonic acid: Physiological roles and potential health benefits - A review. J. Adv. Res., 2017, 11, 33-41.
[http://dx.doi.org/10.1016/j.jare.2017.11.004] [PMID: 30034874]
[29]
Li, P.L. Rats with LC-Q/TOF-MS-based Metabolomics Intervention of Taohongsiwu tang on Blood Stasis Model. Gansu Nongye Daxue Xuebao, 2016, 1-70.
[30]
Zhu, M.D.; Du, W.X.; Wei, C.C. Metabonomic Study on coronary heart disease patients with different. J. Tradit. Chin. Med., 2013, 54(17), 1489-1493.
[31]
Liu, R.H.; Jiang, W.B.; Yu, D.Q. Structure, metabolic pathway and function of plant sphingolipids. Zhiwu Xuebao, 2009, 44(5), 619-628.
[32]
Krystian, M.; Simon, L.; Dorothée, G. Sphingolipids: promising lipid-class molecules with potential applications for industry. Biotechnol. Agron. Soc., 2016, 20, 321-336.
[33]
Tom, A.; Nair, K.S. Assessment of branched-chain amino Acid status and potential for biomarkers. J. Nutr., 2006, 136(1)(Suppl.), 324S-330S.
[http://dx.doi.org/10.1093/jn/136.1.324S] [PMID: 16365107]
[34]
Brosnan, J.T.; Brosnan, M.E. Branched-chain amino acids: enzyme and substrate regulation. J. Nutr., 2006, 136(1)(Suppl.), 207S-211S.
[http://dx.doi.org/10.1093/jn/136.1.207S] [PMID: 16365084]
[35]
Lyu, Z.; Meng, Q.H. Progress in application of branched-chain amino acids in patients with liver cirrhosis. Department of Critical Care Medicine of Liver Disease. J. Clin. Exp. Hepatol., 2015, 31(3), 475-477.
[36]
Czarnecka, A.; Milewski, K.; Zielińska, M. Asymmetric Dimethylarginine and hepatic encephalopathy: cause, effect or association? Neurochem. Res., 2017, 42(3), 750-761.
[http://dx.doi.org/10.1007/s11064-016-2111-x] [PMID: 27885576]
[37]
Carnicer, R.; Crabtree, M.J.; Sivakumaran, V.; Casadei, B.; Kass, D.A. Nitric oxide synthases in heart failure. Antioxid. Redox Signal., 2013, 18(9), 1078-1099.
[http://dx.doi.org/10.1089/ars.2012.4824] [PMID: 22871241]
[38]
Bryant, C.E.; Allcock, G.H.; Warner, T.D. Comparison of effects of chronic and acute administration of NG-nitro-L-arginine methyl ester to the rat on inhibition of nitric oxide-mediated responses. Br. J. Pharmacol., 1995, 114(8), 1673-1679.
[http://dx.doi.org/10.1111/j.1476-5381.1995.tb14956.x] [PMID: 7541283]
[39]
Yang, M.; Ruan, J.; Fu, P.P.; Lin, G. Cytotoxicity of pyrrolizidine alkaloid in human hepatic parenchymal and sinusoidal endothelial cells: Firm evidence for the reactive metabolites mediated pyrrolizidine alkaloid-induced hepatotoxicity. Chem. Biol. Interact., 2016, 243, 119-126.
[http://dx.doi.org/10.1016/j.cbi.2015.09.011] [PMID: 26365561]
[40]
Kumar, S.; DeLeve, L.D.; Kamath, P.S.; Tefferi, A. Hepatic veno-occlusive disease (sinusoidal obstruction syndrome) after hematopoietic stem cell transplantation. Mayo Clin. Proc., 2003, 78(5), 589-598.
[http://dx.doi.org/10.4065/78.5.589] [PMID: 12744547]


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 16
ISSUE: 8
Year: 2020
Published on: 27 September, 2020
Page: [1121 - 1129]
Pages: 9
DOI: 10.2174/1573412915666190802142911
Price: $65

Article Metrics

PDF: 20
HTML: 1