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The synergism mechanism of Rhubarb Anthraquinones on constipation elucidated by comparative pharmacokinetics of Rhubarb extract between normal and diseased rats

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Abstract

In the study, it was hypothesized that Rhubarb Anthraquinones synergistically enhanced the purgative effect on constipation rat from the direct and indirect pathway at the same time. A validated HPLC method was successfully applied to elucidate the synergism mechanism from pharmacokinetics aspect after oral administration of Rhubarb extract with a dose of 0.25 g to normal and constipation rats. Comparison of the pharmacokinetic data of normal and constipation rats showed that there were significant differences (p < 0.05) in the main pharmacokinetic parameters. The C max and AUC of emodin in constipation rats were about ten times that of normal rats, while the t 1/2 was remarkably decreased (p < 0.05). However, a significant decrease (p < 0.05) in AUC value for aloe-emodin and rhein was observed in model group compared with normal group. The results may be attributed to the direct action of aloe-emodin and rhein on intestinal cell membranes and the indirect action of emodin on bowel movement through the adjustment by nervous system.

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References

  • Ali S, Watson MS, Osborne RH (2004) The stimulant cathartic, emodin, contracts the rat isolated ileum by triggering release of endogenous acetylcholine. Auton Autacoid Pharmacol 24:103–105. doi:10.1111/j.1474-8673.2004.00321.x

    Article  CAS  PubMed  Google Scholar 

  • Chen D, Xiong Y, Wang L, Lv B, Lin Y (2012) Characteristics of emodin on modulating the contractility of jejunal smooth muscle. Can J Physiol Pharmacol 90(4):455–462. doi:10.1139/y2012-004

    Article  CAS  PubMed  Google Scholar 

  • Feng SX, Li JS, Qu LB, Shi YM, Zhao D (2013) Comparative pharmacokinetics of five Rhubarb Anthraquinones in normal and thrombotic focal cerebral ischemia-induced rats. Phytother res 27(10):1489–1494. doi:10.1002/ptr.4890

    CAS  PubMed  Google Scholar 

  • Gong HL, Tang WF, Wang H, Xia Q, Huang X (2011) Effects of food and gender on the pharmacokinetics of rhein and emodin in rats after oral dosing with Da-Cheng-Qi decoction. Phytother Res 25:74–80. doi:10.1002/ptr.3223

    Article  CAS  PubMed  Google Scholar 

  • Hamza AA (2010) Ameliorative effects of Moringa oleifera lamseed extract on liver fibrosis in rats. Food Chem Toxicol 48:345–355. doi:10.1016/j.fct.2009.10.022

    Article  CAS  PubMed  Google Scholar 

  • He B, Li Q, Jia Y, Zhao L, Xiao F, Lv C, Xu H, Chen X, Bi K (2012) A UFLC-MS/MS method for simultaneous quantitation of spinosin, mangiferin and ferulic acid in rat plasma: application to a comparative pharmacokinetic study in normal and insomnic rats. J Mass Spectrom 47:1333–1340. doi:10.1002/jms.3072

    Article  CAS  PubMed  Google Scholar 

  • Kento T, Hiroyuki T, Takashi I, Nobuyuki O (2012) The influence of rhein 8-O-β-D-glucopyranoside on the purgative action of sennoside A from rhubarb in mice. Biol Pharm Bull 35:2204–2208. doi:10.1248/bpb.b12-00632

    Article  Google Scholar 

  • Knowles CH, Martin JE (2000) Slow transit constipation: a model of human gut dysmotility. Rev possible aetiologies. Neurogastroenterol Mot 12:181–196. doi:10.1046/j.1365-2982.2000.00198.x

    Article  CAS  Google Scholar 

  • Lee JH, Kim JM, Kim C (2003) Pharmacokinetic analysis of rhein in Rheum undulatum L. J Ethnopharmacol 84:5–9. doi:10.1016/S0378-8741(02)00222-2

    Article  CAS  PubMed  Google Scholar 

  • Liu C, Sun M, Wang L, Wang G, Chen G, Liu C, Liu P (2008) Effects of Yinchenhao Tang and related decoctions on DMN-induced cirrhosis/fibrosis in rats. Chin Med 3:1. doi:10.1186/1749-8546-3-1

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Lou JL, Jiang MN, Li C, Zhou Q, He X, Lei HY, Li J, Jia YJ (2010) Herb medicine Gan-fu-kang attenuates liver injury in a rat fibrotic model. J Ethnopharmacol 128:131–138. doi:10.1016/j.jep.2009.12.038

    Article  PubMed  Google Scholar 

  • Lv C, Li Q, Zhang Y, Sui Z, He B, Xu H, Yin Y, Chen X, Bi K (2013) A UFLC-MS/MS method with a switching ionization mode for simultaneous quantitation of polygalaxanthone III, four ginsenosides and tumulosic acid in rat plasma: application to a comparative pharmacokinetic study in normal and Alzheimer’s disease rats. J Mass Spectrom 48:904–913. doi:10.1002/jms.3230

    Article  CAS  PubMed  Google Scholar 

  • Ma T, Qi QH, Xu J, Dong ZL, Yang WX (2004) Signal pathways involved in emodin-induced contraction of smooth muscle cells from rat colon. World J Gastroenterol 10:1476–1479. doi:10.1046/j.1526-4610.42.s2.7.x

    CAS  PubMed  Google Scholar 

  • Miyoshi A, Masamune O, Fukutomi H, Mori H, Miwa T, Kojima K, Aono M, Nakajima M (1994) The clinical effect of TSUMURA daio-kanz-to extract granules for ethical use (TJ-84) by double blind test against the constipation. Gastroenterology 18:299–312

    Google Scholar 

  • Newall CA, Anderson LA, Phillipson JD (1996) Herbal medicines. The Pharmaceutical Press, London, p 228

    Google Scholar 

  • Peng C, Wang L, Zhao XM (2007) Establishment and evaluation on SD rats model with yang-deficiency and constipation. Chinese Pharmacol Bull 23:407–409. doi:10.3321/j.issn:1001-1978.2007.03.029

    Google Scholar 

  • Sydiskis RJ, Owen DG, Lohr JL, Rosler KH, Blomster RN (1991) Inactivation of enveloped viruses by anthraquinones extracted from plants. Antimicrob Agents Chemother 35:2463–2466. doi:10.1128/AAC.35.12.2463

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Takayama K, Tsutsumi H, Ishizu T, Okamura N (2012) The influence of rhein 8-O-β-D-glucopyranoside on the purgative action of sennoside A from rhubarb in mice. Biol Pharm Bull 35(12):2204–2208. doi:10.1248/bpb.b12-00632

    Article  CAS  PubMed  Google Scholar 

  • Tang W, Eisenbrand G (1992) Chinese drugs of plant origin. Springer, Berlin, p 855

    Book  Google Scholar 

  • Wang L (2005) Study on the treatment effect and mechanism of the compatibility of Radix et Rhizoma Rhei and Radix Aconiti Lateralis Praeparata on yang-deficiency and constipation model. Dissertation, Chengdu University of Traditional Chinese Medicine

  • Wu W, Yan R, Yao M, Zhan Y, Wang Y (2013) Pharmacokinetics of anthraquinones in rat plasma after oral administration of a rhubarb extract. Biomed Chromatogr. doi:10.1002/bmc.3070

    Google Scholar 

  • Xie PS, Leung AY (2009) Understanding the traditional aspect of Chinese medicine in order to achieve meaningful quality control of Chinese materia medica. J Chromatogr A 1216:1933–1940. doi:10.1016/j.chroma.2008.08.045

    Article  CAS  PubMed  Google Scholar 

  • Xu JD, Liu S, Wang W, Li LS, Li XF, Li Y, Guo H, Ji T, Feng XF, Hou XL, Zhang Y, Zhu JX (2012) Emodin induces chloride secretion in rat distal colon through activation of mast cells and enteric neurons. Br J Pharmacol 165:197–207. doi:10.1111/j.1476-5381.2011.01573.x

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Yagi T, Yamauchi K (1999) Synergistic effects of anthraquinones on the purgative activity of rhein anthrone in mice. J Pharm Pharmacol 51:93–95. doi:10.1211/0022357991772007

    CAS  PubMed  Google Scholar 

  • Yagi T, Yamauchi K, Kuwano S (1997) The synergistic purgative action of aloe-emodin anthrone and rhein anthrone in mice: synergism in large intestinal propulsion and water secretion. J Pharm Pharmacol 49:22–25. doi:10.1111/j.2042-7158.1997.tb06745.x

    Article  CAS  PubMed  Google Scholar 

  • Yan DM, Ma YM (2007) Simultaneous quantification of five anthraquinones in rat plasma by high-performance liquid chromatography with fluorescence detection. Biomed Chromatogr 21:502–507. doi:10.1002/bmc.784

    Article  CAS  PubMed  Google Scholar 

  • Yan DM, Ma YM, Shi R, Xu DS, Zhang N (2009) Pharmacokinetics of anthraquinones in Xiexin decoction and in different combinations of its constituent herbs. Phytother Res 23:317–323. doi:10.1002/ptr.2622

    Article  CAS  PubMed  Google Scholar 

  • Yang ZH, Yu HJ, Pan A, Du JY, Ruan YC, Ko WH, Chan HC, Zhou WL (2008) Cellular mechanisms underlying the laxative effect of flavonol naringenin on rat constipation model. PLos One 3:3348. doi:10.1371/journal.pone.0003348

    Article  Google Scholar 

  • Zhang HL, Tang ZY, Yang JX, Zhang Y, Li Y, Lin Y (2006) Bi-directional regulation of emodin and quercetin on smooth muscle myosin of gizzard. FEBS Lett 580:469–473. doi:10.1016/j.febslet.2005.12.041

    Article  CAS  PubMed  Google Scholar 

  • Zhang YX, Li JS, Peng WW, Liu X, Yang GM, Chen LH, Cai BC (2013) Comparative pharmacokinetics of aloe-emodin, rhein and emodin determined by liquid chromatography-mass spectrometry after oral administration of a rhubarb peony decoction and rhubarb extract to rats. Pharmazie 68:333–339. doi:10.1691/ph.2013.2855

    CAS  PubMed  Google Scholar 

  • Zheng YF, Liu CF, Lai WF, Xiang Q, Li ZF, Wang H, Lin N (2014) The laxative effect of emodin is attributable to increased aquaporin 3 expression in the colon of mice and HT-29 cells. Fitoterapia. doi:10.1016/j.fitote.2014.04.002

    Google Scholar 

  • Zheyu C, Qinghui QI, Lixin L, Tao MA, Xu J, Zhang L, Zhang L, Lunan Y (2006) Effects of emodin on Ca2+ signal transduction of smooth muscle cells in multiple organ dysfunction syndrome. J Surg Res 131:80–85. doi:10.1016/j.jss.2005.08.031

    Article  PubMed  Google Scholar 

  • Zhu W, Zhang L, Wang XM, Wang BX, Li XY (2005) The pharmacokinetics of rhein in 12 healthy volunteers after oral administration of rhubarb extract. China J Chin Mater Med 30:1458–1461. doi:10.3321/j.issn:1001-5302.2005.18.021

    Google Scholar 

Download references

Acknowledgments

The study was supported by National Natural Science Foundation of China (No: 81373943); the National Basic Research Program of China (973 Program No: 2011BAI13B05, 2012CB723502), Sichuan Youth Science and Technology Fundation (2013JQ0018) and Sichuan Provincial Science and Technology Department of Youth Science and Technology Innovation Research Team Program-Sichuan Province Pharmacology of Traditional Chinese Medicine Science and Technology Innovation Youth Team(2014TD0007).

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Correspondence to Cheng Peng or Yun-xia Li.

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Gong, Xh., Li, Y., Zhang, Rq. et al. The synergism mechanism of Rhubarb Anthraquinones on constipation elucidated by comparative pharmacokinetics of Rhubarb extract between normal and diseased rats. Eur J Drug Metab Pharmacokinet 40, 379–388 (2015). https://doi.org/10.1007/s13318-014-0216-7

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