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Planta Med 2015; 81(09): 722-732
DOI: 10.1055/s-0035-1545915
Biological and Pharmacological Activity
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Metabonomic Study of the Effects of Acanthopanax senticosus on Peripheral System of Rats

Shuai-nan Zhang   *
1   Chinese Medicine Toxicological Laboratory, Heilongjiang University of Chinese Medicine, Harbin, P. R. China
,
Xu-zhao Li   *
1   Chinese Medicine Toxicological Laboratory, Heilongjiang University of Chinese Medicine, Harbin, P. R. China
,
Shu-min Liu
1   Chinese Medicine Toxicological Laboratory, Heilongjiang University of Chinese Medicine, Harbin, P. R. China
2   Drug Safety Evaluation Center, Heilongjiang University of Chinese Medicine, Harbin, P. R. China
,
Fang Lu
1   Chinese Medicine Toxicological Laboratory, Heilongjiang University of Chinese Medicine, Harbin, P. R. China
› Author Affiliations
Further Information

Publication History

received 11 November 2014
revised 08 March 2015

accepted 10 March 2015

Publication Date:
29 April 2015 (online)

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Abstract

Acanthopanax senticosus is extensively used to treat various nervous and cerebrovascular diseases in traditional medicinal systems in China and Russia. Ultrahigh-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry coupled with pattern recognition methods was used to investigate the effects of A. senticosus on the peripheral system in rats. The analysis of possible pathways influenced by A. senticosus was performed with MetaboAnalyst and Cytoscape software. After treatment with A. senticosus, 21 modulated metabolites in heart tissue, 20 in liver tissue, 14 in spleen tissue, 17 in lung tissue, 16 in kidney tissue, and 12 in a serum sample were identified and considered potential biomarkers of A. senticosus treatments. The regulation of some endogenous metabolites by A. senticosus could be beneficial for the treatment of several peripheral system diseases, such as hypertension, cancer, and oxidative stress, etc. However, there were also some upregulated endogenous metabolites producing potential toxicity to the peripheral system. A metabonomic analysis revealed that protection and toxicity coexisted in the effects of A. senticosus on the peripheral system, which may be a practical guide for its safe use and beneficial to the expansion of its application.

Key words

Acanthopanax senticosus - Araliaceae - metabonomic analysis - potential intervention targets - peripheral system

* Both of these authors contributed equally to this work.


Supporting Information

 

  • References

  • 1 Li XZ, Zhang SN, Liu SM, Lu F. Recent advances in herbal medicines treating Parkinsonʼs disease. Fitoterapia 2013; 84: 273-285
    CrossrefPubMedGoogle Scholar
  • 2 Li XZ, Zhang SN, Wang KX, Liu HY, Yang ZM, Liu SM, Lu F. Neuroprotective effects of extract of Acanthopanax senticosus harms on SH-SY5Y cells overexpressing wild-type or A53 T mutant α-synuclein. Phytomedicine 2014; 21: 704-711
    CrossrefPubMedGoogle Scholar
  • 3 Wu F, Li H, Zhao L, Li X, You J, Jiang Q, Li S, Jin L, Xu Y. Protective effects of aqueous extract from Acanthopanax senticosus against corticosterone-induced neurotoxicity in PC12 cells. J Ethnopharmacol 2013; 148: 861-868
    CrossrefPubMedGoogle Scholar
  • 4 Li XZ, Zhang SN, Lu F, Liu CF, Wang Y, Bai Y, Wang N, Liu SM. Cerebral metabonomics study on Parkinsonʼs disease mice treated with extract of Acanthopanax senticosus harms. Phytomedicine 2013; 20: 1219-1229
    CrossrefPubMedGoogle Scholar
  • 5 Liu SM, Li XZ, Huo Y, Lu F. Protective effect of extract of Acanthopanax senticosus Harms on dopaminergic neurons in Parkinsonʼs disease mice. Phytomedicine 2012; 19: 631-638
    CrossrefPubMedGoogle Scholar
  • 6 Lee D, Park J, Yoon J, Kim MY, Choi HY, Kim H. Neuroprotective effects of Eleutherococcus senticosus bark on transient global cerebral ischemia in rats. J Ethnopharmacol 2012; 139: 6-11
    CrossrefPubMedGoogle Scholar
  • 7 Huang LZ, Huang BK, Ye Q, Qin LP. Bioactivity-guided fractionation for anti-fatigue property of Acanthopanax senticosus . J Ethnopharmacol 2011; 133: 213-219
    CrossrefPubMedGoogle Scholar
  • 8 Xu Y, Han C, Xu S, Yu X, Jiang G, Nan C. Effects of Acanthopanax senticosus on learning and memory in a mouse model of Alzheimerʼs disease and protection against free radical injury to brain tissue. NRR 2008; 3: 192-195
    PubMedGoogle Scholar
  • 9 Lu F, Sun Q, Bai Y, Bao SR, Li XZ, Yan GL, Liu SM. Characterization of eleutheroside B metabolites derived from an extract of Acanthopanax senticosus Harms by high-resolution liquid chromatography/quadrupole time-of-flight mass spectrometry and automated data analysis. Biomed Chromatogr 2012; 26: 1269-1275
    CrossrefPubMedGoogle Scholar
  • 10 Liu SM, Sun Q, Bai Y, Lu F, Yan GL, Bao SR. Analysis on isofraxidin contained in Acanthopanax senticosus extracts and its metabolites by UPLC-Q-TOF-MS and automatic data processing technique. China J Chin Materia Medica 2012; 37: 1840-1844
    PubMedGoogle Scholar
  • 11 Sun Q, Bai Y, Bao SR, Lu F, Yan GL, Liu SM. UPLC-Q-TOF-MS and automated data analysis of eleutherosideD derived from extract of Acanthopanax senticosus Harm and its metabolites. Pharmacol Clin Chin Materia Medica 2012; 28: 38-42
    PubMedGoogle Scholar
  • 12 Zhang SN, Li XZ, Wang Y, Zhang N, Yang ZM, Liu SM, Lu F. Neuroprotection or neurotoxicity? new insights into the effects of Acanthopanax senticosus harms on nervous system through cerebral metabolomics analysis. J Ethnopharmacol 2014; 156: 290-300
    CrossrefPubMedGoogle Scholar
  • 13 Lu F, Cao M, Wu B, Li XZ, Liu HY, Chen DZ, Liu SM. Urinary metabonomics study on toxicity biomarker discovery in rats treated with Xanthii Fructus. J Ethnopharmacol 2013; 149: 311-320
    CrossrefPubMedGoogle Scholar
  • 14 Gao D, Jin F, Liu H, Wang Y, Jiang Y. Metabonomic study on the antitumor effect of flavonoid derivative 3 d in HepG2 cells and its action mechanism. Talanta 2014; 118: 382-388
    CrossrefPubMedGoogle Scholar
  • 15 Zhao YY, Cheng XL, Cui JH, Yan XR, Wei F, Bai X, Lin RC. Effect of ergosta-4, 6, 8(14), 22-tetraen-3-one (ergone) on adenine-induced chronic renal failure rat: a serum metabonomic study based on ultra performance liquid chromatography/high-sensitivity mass spectrometry coupled with MassLynx i-FIT algorithm. Clin Chim Acta 2012; 413: 1438-1445
    CrossrefPubMedGoogle Scholar
  • 16 Creek DJ, Dunn WB, Fiehn O, Griffin JL, Hall RD, Lei Z, Mistrik R, Neumann S, Schymanski EL, Sumner LW. Metabolite identification: are you sure? And how do your peers gauge your confidence?. Metabolomics 2014; 10: 350-353
    CrossrefPubMedGoogle Scholar
  • 17 Varela-Rey M, Iruarrizaga-Lejarreta M, Lozano JJ, Aransay AM, Fernandez AF, Lavin JL, Mosen-Ansorena D, Berdasco M, Turmaine M, Luka Z, Wagner C, Lu SC, Esteller M, Mirsky R, Jessen KR, Fraga MF, Martinez-Chantar ML, Mato JM, Woodhoo A. S-adenosylmethionine levels regulate the schwann cell DNA methylome. Neuron 2014; 81: 1024-1039
    CrossrefPubMedGoogle Scholar
  • 18 van Driel LM, de Jonge R, Helbing WA, van Zelst BD, Ottenkamp J, Steegers EA, Steegers-Theunissen RP. Maternal global methylation status and risk of congenital heart diseases. Obstet Gynecol 2008; 112: 277-283
    CrossrefPubMedGoogle Scholar
  • 19 Boyacioglu M, Turgut H, Akgullu C, Eryilmaz U, Kum C, Onbasili OA. The effect of L-carnitine on oxidative stress responses of experimental contrast-induced nephropathy in rats. J Vet Med Sci 2014; 76: 1-8
    CrossrefPubMedGoogle Scholar
  • 20 Ueland T, Svardal A, Oie E, Askevold ET, Nymoen SH, Bjorndal B, Dahl CP, Gullestad L, Berge RK, Aukrust P. Disturbed carnitine regulation in chronic heart failure–increased plasma levels of palmitoyl-carnitine are associated with poor prognosis. Int J Cardiol 2013; 167: 1892-1899
    CrossrefPubMedGoogle Scholar
  • 21 Dinicolantonio JJ, Niazi AK, McCarty MF, Lavie CJ, Liberopoulos E, OʼKeefe JH. L-carnitine for the treatment of acute myocardial infarction. Rev Cardiovasc Med 2014; 15: 52-62
    PubMedGoogle Scholar
  • 22 Costa CG, Struys EA, Bootsma A, ten Brink HJ, Dorland L, Tavares de Almeida I, Duran M, Jakobs C. Quantitative analysis of plasma acylcarnitines using gas chromatography chemical ionization mass fragmentography. J Lipid Res 1997; 38: 173-182
    PubMedGoogle Scholar
  • 23 Schiff M, Mohsen AW, Karunanidhi A, McCracken E, Yeasted R, Vockley J. Molecular and cellular pathology of very-long-chain acyl-CoA dehydrogenase deficiency. Mol Genet Metab 2013; 109: 21-27
    CrossrefPubMedGoogle Scholar
  • 24 Jacobs RL, da Silva R, Nelson R. Creatine Supplementation may prevent NAFLD by stimulating fatty acid oxidation. FASEB J 2013; 27: 222.2
    PubMedGoogle Scholar
  • 25 Ito S, Kusuhara H, Kumagai Y, Moriyama Y, Inoue K, Kondo T, Nakayama H, Horita S, Tanabe K, Yuasa H, Sugiyama Y. N-methylnicotinamide is an endogenous probe for evaluation of drug-drug interactions involving multidrug and toxin extrusions (MATE1 and MATE2-K). Clin Pharmacol Ther 2012; 92: 635-641
    CrossrefPubMedGoogle Scholar
  • 26 Zanatta A, Moura AP, Tonin AM, Knebel LA, Grings M, Lobato VA, Ribeiro CA, Dutra-Filho CS, Leipnitz G, Wajner M. Neurochemical evidence that the metabolites accumulating in 3-methylcrotonyl-CoA carboxylase deficiency induce oxidative damage in cerebral cortex of young rats. Cell Mol Neurobiol 2013; 33: 137-146
    CrossrefPubMedGoogle Scholar
  • 27 Matsui A, Psacharopoulos HT, Mowat AP, Portmann B, Murphy GM. Radioimmunoassay of serum glycocholic acid, standard laboratory tests of liver function and liver biopsy findings: comparative study of children with liver disease. J Clin Pathol 1982; 35: 1011-1017
    CrossrefPubMedGoogle Scholar
  • 28 Lawler JM, Barnes WS, Wu G, Song W, Demaree S. Direct antioxidant properties of creatine. Biochem Biophys Res Commun 2002; 290: 47-52
    CrossrefPubMedGoogle Scholar
  • 29 Aly AM, Arai M, Hoyer LW. Cysteamine enhances the procoagulant activity of Factor VIII-East Hartford, a dysfunctional protein due to a light chain thrombin cleavage site mutation (arginine-1689 to cysteine). J Clin Invest 1992; 89: 1375-1381
    CrossrefPubMedGoogle Scholar
  • 30 Bakovic D, Pivac N, Eterovic D, Breskovic T, Zubin P, Obad A, Dujic Z. The effects of low-dose epinephrine infusion on spleen size, central and hepatic circulation and circulating platelets. Clin Physiol Funct Imaging 2013; 33: 30-37
    CrossrefPubMedGoogle Scholar
  • 31 Ryan AJ, McCoy DM, McGowan SE, Salome RG, Mallampalli RK. Alveolar sphingolipids generated in response to TNF-alpha modifies surfactant biophysical activity. J Appl Physiol (1985) 2003; 94: 253-258
    CrossrefPubMedGoogle Scholar
  • 32 Huang DB, Ran RZ, Yu ZF. [Effect of Acanthopanax senticosus injection on the activities of human tumor necrosis factor and natural killer cell in blood in the patients with lung cancer]. Zhongguo Zhong Yao Za Zhi 2005; 30: 621-624
    PubMedGoogle Scholar
  • 33 Yoon TJ, Yoo YC, Lee SW, Shin KS, Choi WH, Hwang SH, Ha ES, Jo SK, Kim SH, Park WM. Anti-metastatic activity of Acanthopanax senticosus extract and its possible immunological mechanism of action. J Ethnopharmacol 2004; 93: 247-253
    CrossrefPubMedGoogle Scholar
  • 34 Cattaneo MG, Palazzi E, Bondiolotti G, Vicentini LM. 5-HT1D receptor type is involved in stimulation of cell proliferation by serotonin in human small cell lung carcinoma. Eur J Pharmacol 1994; 268: 425-430
    CrossrefPubMedGoogle Scholar
  • 35 Chien SJ, Lin KM, Kuo HC, Huang CF, Lin YJ, Huang LT, Tain YL. Two different approaches to restore renal nitric oxide and prevent hypertension in young spontaneously hypertensive rats: l-citrulline and nitrate. Transl Res 2014; 163: 43-52
    CrossrefPubMedGoogle Scholar
  • 36 Miyashita M, Sadzuka Y. Improvements of doxorubicin-induced antitumor activity and adverse reaction by combined citrulline. Biol Pharm Bull 2014; 37: 447-453
    CrossrefPubMedGoogle Scholar
  • 37 El-Hattab AW, Emrick LT, Chanprasert S, Craigen WJ, Scaglia F. Mitochondria: role of citrulline and arginine supplementation in MELAS syndrome. Int J Biochem Cell Biol 2014; 48: 85-91
    CrossrefPubMedGoogle Scholar
  • 38 Kim HL, Choi YK, Kim do H, Park SO, Han J, Park YS. Tetrahydropteridine deficiency impairs mitochondrial function in Dictyostelium discoideum Ax2. FEBS Lett 2007; 581: 5430-5434
    CrossrefPubMedGoogle Scholar
  • 39 Polimeni A, Curcio A, Indolfi C. Renal sympathetic denervation for treating resistant hypertension. Circ J 2013; 77: 857-863
    CrossrefPubMedGoogle Scholar
  • 40 Quinn P, Borkowski KR, Collis MG. Epinephrine enhances neurogenic vasoconstriction in the rat perfused kidney. Hypertension 1985; 7: 47-52
    CrossrefPubMedGoogle Scholar
  • 41 Neubauer B, Machura K, Chen M, Weinstein LS, Oppermann M, Sequeira-Lopez ML, Gomez RA, Schnermann J, Castrop H, Kurtz A, Wagner C. Development of vascular renin expression in the kidney critically depends on the cyclic AMP pathway. Am J Physiol Renal Physiol 2009; 296: F1006-F1012
    CrossrefPubMedGoogle Scholar
  • 42 Nitto T, Inoue T, Node K. Alternative spliced variants in the pantetheinase family of genes expressed in human neutrophils. Gene 2008; 426: 57-64
    CrossrefPubMedGoogle Scholar
  • 43 Campbell WB, Gauthier KM. Inducible endothelium-derived hyperpolarizing factor: role of the 15-lipoxygenase-EDHF pathway. J Cardiovasc Pharmacol 2013; 61: 176-187
    CrossrefPubMedGoogle Scholar
  • 44 WHO. Radix Eleutherococci. WHO monographs on selected medicinal plants, Vol. 2. Geneva: WHO; 2004: 83-96
    Google Scholar
  • 45 Li XZ, Zhang SN, Wang KX, Liu SM, Lu F. iTRAQ-based quantitative proteomics study on the neuroprotective effects of extract of Acanthopanax senticosus harm on SH-SY5Y cells overexpressing A53 T mutant alpha-synuclein. Neurochem Int 2014; 72: 37-47
    CrossrefPubMedGoogle Scholar