Advertisement

Antipyretic effect of Herba Ephedrae-Ramulus Cinnamomi herb pair on yeast-induced pyrexia rats: A metabolomics study

  • Xiao-ming Wang
  • Wen-jie Xu
  • Liang-kui Xu
  • Shuai Song
  • Xue-feng Xing
  • Jia-bo Luo
Original Article
  • 32 Downloads

Abstract

Objective

To investigate the antipyretic mechanism of Herba Ephedrae (Eph)-Ramulus Cinnamomi (RC) herb pair on yeast-induced pyrexia in rats.

Methods

Totally 30 qualifified male SD rats were randomly assigned to the normal control (NC) group, the pyrexia model (model) group, the Eph, RC and Eph-RC treatment groups by a random digital table, 6 rats in each group. Each rat received a 20% aqueous suspension of yeast (10 mL/kg) except the NC group. The 3 treatment groups were administered 8.1, 5.4 and 13.5 g/kg Eph, RC and Eph-RC respectively at 5 and 12 h after yeast injection, the NC group and the model groups were administered equal volume of distilled water. Rectal temperatures were measured at 0, 6, 8, 10, 12, 15, 18, 24 and 30 h and urine was collected prior to yeast injection and at 6, 10, 18, 24, 30, and 36 h after yeast injection. Then urine metabolomic profifiling by gas chromatography tandem mass spectrometry, coupled with multivariate statistical analysis and pattern recognition techniques were used to explore the antipyretic effects of Eph-RC. Partial least squares discriminate analysis was used to analyze the metabolomics dataset including classifification and regression in metabolomics plot profifiling.

Results

Compared with the NC group, rectal temperatures were signifificantly higher in the model group (P<0.01), while 3 treatment groups decreased signifificantly compared with the model group (P<0.05 or P<0.01). Rectal temperatures of Eph-RC-treated rats started to go down at 6 h, and markedly decreased at 8, 12, 15, 18 and 24 h (P<0.05 or P<0.01), while those of the Eph and RC groups had decreased fifirstly at 8 h and were markedly lower at 12 h (P<0.05 or P<0.01). Seventeen potential biomarkers related to pyrexia were confifirmed and identifified, including pyruvic acid, L-phenylalanine, L-tyrosine, phenylacetic acid, hippuric acid, succinic acid, citrate and so on. Eight potential alterations of metabolic pathways including phenylalanine metabolism, citrate cycle, tryptophan metabolism, biosynthesis of valine, leucine and isoleucine, were identifified in relation to the antipyretic effects of Eph-RC using MetPA software.

Conclusion

The antipyretic effect of Eph-RC herb pair on yeast-induced pyrexia in rats involved correction of perturbed amino acid, fatty acid, and carbohydrate metabolism according to the metabolic pathway analysis with MetPA.

Keywords

Chinese medicine Herba Ephedrae Ramulus Cinnamomi herb pair principal component analysis partial least squares-discriminant analysis biomarker 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Supplementary material

11655_2017_2778_MOESM1_ESM.pdf (259 kb)
Supplementary material, approximately 260 KB.

References

  1. 1.
    Mackowiak PA, ed. Mandell, Douglas, and Bennett's principles and practise of infectious disease. 6th ed. Philadelphia: Natasha Andjelkovic Publishing House; 2005:703–718.Google Scholar
  2. 2.
    Mei F, Xing XX, Tang QF, Chen FL, Guo Y, Song S, et al. Antipyretic and anti-asthmatic activities of traditional Chinese herb-pairs, Ephedra and Gypsum. Chin J Integr Med 2016;22:445–450.CrossRefPubMedGoogle Scholar
  3. 3.
    Xie XH, Dong J, Fu YM, Tang HM. Study on antipyretic effect and mechanism of Fructus Lonicerae on IL-1ß-induced fever in rabbits. Lishizhen Med Mater Med Res (Chin) 2007;18:2071–2073.Google Scholar
  4. 4.
    Huang L, Liu JF, Liu LX, Li DF, Zhang Y, Nui HZ, et al. Studies on the antipyretic and anti-inflammatory effects of Artemisia annua L. Chin J Chin Mater Med (Chin) 1993;18:44–48.Google Scholar
  5. 5.
    He Y, Zhu Y, Zhang R, Ge L, Wan H. Simultaneous quantification of nine major active components in traditional Chinese prescription Mahuang decoction and the infl uence of herbal compatibility on their contents. Pharmacogn Mag 2014;10:S72–S79.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Wang JB, Li ZY, Wang XH. Clinical application of Ephedra decoction. Chin J Ethnomed Ethnopham (Chin) 2011;10:57–58.Google Scholar
  7. 7.
    Wu GR, Wang XW. The pharmaceutical study of pseudophedrine salicylate (?) antipyretic–action and the effects on heart rate, blood pressure and histamine-induced allergic reations. Prog Pharm Sci (Chin) 2000;24:238–241.Google Scholar
  8. 8.
    Ge W, Li HB, Yu Y, Fang B, Yao XS. Research progress on chemical constituents, pharmacological action, and clinical application of reduning injection. Chin Tradit Herb Drugs (Chin) 2017;48:1027–1036.Google Scholar
  9. 9.
    Zhang LQ, Zhang ZG, Fu Y, Xu Y. Research progress of trans-cinnamaldehyde pharmacological effects. Chin J New Drugs (Chin) 2015;40:4568–4572.Google Scholar
  10. 10.
    Xie B, Gong T, Gao R, Liu J, Zuo J, Wang X, et al. Development of rat urinary HPLC-UV profiling for metabolomics study on Liuwei Dihuang Pills. J Pharm Biomed Anal 2009;49:492–497.CrossRefPubMedGoogle Scholar
  11. 11.
    Gavaghan CL, Nicholson JK, Connor SC, Wilson ID, Wright B, Holmes E. Directly coupled high-performance liquid chromatography and nuclear magnetic resonance spectroscopic with chemometric studies on metabolic variation in Sprague-Dawley rats. Anal Biochem 2001;291:245–252.CrossRefPubMedGoogle Scholar
  12. 12.
    Wang XJ, Sun H, Zhang AH, Sun WJ, Wang P, Wang ZG. Potential role of metabolomics approaches in the area of traditional Chinese medicine: as pillars of the bridge between Chinese and Western medicine. J Pharm Biomed Anal 2011;55:859–868.CrossRefPubMedGoogle Scholar
  13. 13.
    Gao P, Lu C, Zhang F, Sang P, Yang D, Li X, et al. Integrated GC-MS and LC-MS plasma metabonomics analysis of ankylosing spondylitis. Analyst 2008;133:1214–1220.CrossRefPubMedGoogle Scholar
  14. 14.
    Hong Z, Lin Z, Liu Y, Tan G, Lou Z, Zhu Z, et al. Innovative microwave-assisted oximation and silylation procedures for metabolomics analysis of plasma samples using gas chromatography-mass spectrometry. J Chromatogr A 2012;1254:14–22.CrossRefPubMedGoogle Scholar
  15. 15.
    Gu Q, David F, Lynen F, Rumpel K, Dugardeyn J, van Der Straeten D, et al. Evaluation of automated sample preparation, retention time locked gas chromatography-mass spectrometry and data analysis methods for the metabolomic study of Arabidopsis species. J Chromatogr A 2011;1218:3247–3254.CrossRefPubMedGoogle Scholar
  16. 16.
    Xu WJ, Fang F, Yu LZ, Luo JB. Studies on antipyretic activity and Its mechanisms of couplet medicines of Herba Ephedrae and Ramulus Cinnamomi. Lishizhen Med Mater Med Res (Chin) 2013;24:1547–1549.Google Scholar
  17. 17.
    Namera A, Yashiki M, Nishida M, Kojima T. Direct extract derivatization for determination of amino acids in human urine by gas chromatography and mass spectrometry. J Chromatogr B 2002;776:49–55.CrossRefGoogle Scholar
  18. 18.
    Huo HR, Tan YQ, Qin CL, Liu T. Effect of Guizhi Decoction on complex pathologic model of spontaneous hypertension with hyperpyxia of rat induced by yeast. Chin J Exp Tradit Med Form (Chin) 2004;10:37–39.Google Scholar
  19. 19.
    Broadley KJ. The vascular effects of trace amines and amphetamines. Pharmacol Ther 2010;125:363–375.CrossRefPubMedGoogle Scholar
  20. 20.
    Lindemann L, Hoener MC. A renaissance in trace amines inspired by a novel GPCR family. Trends Pharmacol 2005;26:274–281.CrossRefGoogle Scholar
  21. 21.
    Wang X, Li J, Dong G, Yue J. The endogenous substrates of brain CYP2D. Eur J Pharmacol 2014;724:211–218.CrossRefPubMedGoogle Scholar
  22. 22.
    Gao XY, Guo MX, Peng L, Zhao BS, Su JK, Liu HY. UPLC Q-TOF/MS-based metabolic profiling of urine reveals the novel antipyretic mechanisms of Qingkailing Injection in a rat model of yeast-induced pyrexia. Evid Based Complement Alternat Med 2013;2013:864747.PubMedPubMedCentralGoogle Scholar
  23. 23.
    Israel G, Stefan RJ, Ophry P. Organic acids: old metabolites, new themes. J Chem Technol Biotechnol 2006;81:1601–1611.CrossRefGoogle Scholar
  24. 24.
    O'Mahony SM, Clarke G, Borre YE, Dinan TG, Cryan JF. Serotonin, tryptophan metabolism and the brain-gutmicrobiome axis. Behav Brain Res 2015;277:32–48.CrossRefPubMedGoogle Scholar

Copyright information

© Chinese Association of the Integration of Traditional and Western Medicine 2017

Authors and Affiliations

  • Xiao-ming Wang
    • 1
    • 2
  • Wen-jie Xu
    • 3
    • 4
  • Liang-kui Xu
    • 1
  • Shuai Song
    • 1
  • Xue-feng Xing
    • 1
  • Jia-bo Luo
    • 1
  1. 1.School of Traditional Chinese Medical SciencesSouthern Medical UniversityGuangzhouChina
  2. 2.School of PharmacyGuangdong Pharmaceutical UniversityGuangzhouChina
  3. 3.Department of Traditional Chinese Medicine PharmaceuticsGuangdong Second Traditional Chinese Medicine HospitalGuangzhouChina
  4. 4.Guangdong Provincial Key Laboratory of Research and Development of Traditional Chinese MedicineGuangdong Province Engineering Technology Research Institute of Traditional Chinese MedicineGuangzhouChina

Personalised recommendations