Archives of Pharmacal Research

, Volume 25, Issue 4, pp 528–533 | Cite as

Antithrombotic and antiallergic activities of rhaponticin from rhei rhizoma are activated by human intestinal bacteria

  • Eun-Kyung Park
  • Min-Kyung Choo
  • Hae-Kyung Yoon
  • Dong-Hyun Kim
Research Articles Articles


To evaluate the antithrombotic and antiallergic properties of rhaponticin extracted from Rhei Rhizoma, thein vitro andex vivo inhibitory activities of rhaponticin and its metabolite, rhapontigenin, were measured. These compounds inhibitedin vitro ADP- and collagen-induced platelet aggregation. Rhapontigenin was more potent, with IC50 values of 4 and 70 μg/ml, respectively. Inex vivo ADP- and collagen-induced rat platelet aggregation, these compounds also exhibited a potent inhibitory effect. The antiplatelet aggregation effects of rhaponticin and rhapontigenin were more potent than those of aspirin. Rhapontigenin showed significant protection from death due to pulmonary thrombosis in mice. Rhapontigenin also showed the strongest inhibitory activity against β-hexosaminidase release induced by DNP-BSA. These compounds inhibited PCA reaction in mice. Rhapontigenin intraperitoneally administered showed the strongest inhibitory activity and significantly inhibited PCA at doses of 25 and 50 mg/kg, with inhibitory activities of 48 and 85%, respectively. The inhibitory activity of orally administered rhaponticin was stronger than that of intraperitoneally administered rhaponticin. These results suggest that rhaponticin, in the rhizome of Rhei Rhizoma, is a prodrug that has extensive antiallergic and antithrombotic properties.

Key words

Antithrombosis Antiallergy Rhaponticin Rhapontigenin Rhei Rhizoma Intestinal bacteria 


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  1. Aronson N.N., and Davidson E.A., Lysosomal hyaluronidase from rat liver. II. Properties.J. Biol. Chem., 242, 441–444 (1967).PubMedGoogle Scholar
  2. Born, G.V.R. and Cross, M.J., The aggregation of blood platelets.J. Physiol., 168, 178–195 (1963).PubMedGoogle Scholar
  3. Choi O.H. Kim J.H. and Kinet J.P., Calcium mobilization via sphingosine kinase in signaling by the Fc epsilon Rl antigen receptor.Nature, 380, 634–636 (1996).PubMedCrossRefGoogle Scholar
  4. Di Minno G., and Silver M., Mouse antithrombotic assay: a simple method for the evaluation of antithrombotic agents in vivo. Potentiation of antithrombotic activity by ethyl alcohol.J. Pharmacol. Exp. Ther., 225, 57–60 (1983).Google Scholar
  5. Kashiwada Y., Nonaka Y. and Nishioka I., Studies on Rhubarb (Rhei Rhizoma) VI. Isolation and characterization of stibene.Chem. Pharm. Bull., 32, 3501–3506 (1984).Google Scholar
  6. Katayama S., Shionoya H., and Ohtake S., A new method for extraction of extravasated dye in the skin and the influence of fasting stress on passive cutaneous anaphylaxis in guinea pigs and rats.Microbiol. Immunol., 22, 89–101 (1978).PubMedCrossRefGoogle Scholar
  7. Kim, D.-H. Y. K.-W., Bae, E.-A., Park, H.J., Choi, J.W., Metabolism of kalopanaxsapon B and H by human intestinal bacteria and antidiabetic activities of their metabolites.Biol. Pharm. Bull., 21, 360–365 (1998).PubMedGoogle Scholar
  8. Kim D.-H., Park, E.-K., Bae, E.-A.,and Han, M.J., Metabolism of rhaponticin and chrysophanol-8-O-b-D-glucopyranoside form the rhizome of Rheum undulatum by human intestinal bacteria and their antiallergic actions.Biol. Pharm. Bull., 23, 430–433 (2000).Google Scholar
  9. Kimura, Y., Tani, T., Kanbe, T. and Watanabe, K., Effect of cilostazol on platelet aggregation and experimental thrombosis.Arzneim., Forsch. Drug Res., 35, 1144–49 (1985).Google Scholar
  10. Ko, S.K., A new stibene diglycoside from Rheum undulatum.Arch. Pharm. Res., 23, 159–162 (2000).PubMedCrossRefGoogle Scholar
  11. Ko, S.K. Whang, W.K., and Kim, I.K., Anthraquinone and stilbene derivatives from the cultivated Korean Rhubarb Rhizomes.Arch. Pharm. Res. 18, 282–288 (1995).CrossRefGoogle Scholar
  12. Kobashi K. and Akao T., Relation of intestinal bacteria to pharmacological effects of glycosides.Biosci. Microflora, 16, 1–7 (1997).Google Scholar
  13. Lee, J.M., Reduohanxiao-tang. In:Longevity and life Preservation in Oriental Medicine. S.H. Choi (translated), Seoul: Kyung Hee Univ. Press, 1996, pp 153–175.Google Scholar
  14. Matsuda H., Tomohiro N., Hirabe K., Harima S., Ko S., Mazuo K., Yoshikawa M., Kubo M., StudDLTKFKAEMFDL.y on Anti-Oketsu Activity of Rhurbarb II., Antiallergic Effects of stibene components from Rhei Rhizoma (Dried Rhizome of Rheum undulatum cultivated in Korea).Biol. Pharm. Bull., 24, 264–267 (2001).PubMedCrossRefGoogle Scholar
  15. MacMahon S., and Sharpe N., Long-term antiplatelet therapy for the prevention of vascular disease.Med. J. Aust., 154, 477–480 (1991).PubMedGoogle Scholar
  16. Okabe H., Matus K., and Nishioka I., Studies on Rhubarb (Rhei Rhizoma) II, Anthraquinone glycosides.Chem. Pharm. Bull., 21, 1254–1260 (1973).Google Scholar
  17. Oshino, H., Naruse Y., and Tsukui M., Quantilative analysis of the purgative components of Rhubarb and Senna.Chem. Pharm. Bull., 26, 2458–2464 (1978).Google Scholar
  18. Packham M.A., Role of platelets in thrombosis and hemostasis.Can. J. Physiol. Pharmacol., 72, 2782–2784 (1994).Google Scholar
  19. Stein B., and Fuster V., Role of platelet inhibitor therapy in myocardial infarction.Cardiovasc. Drugs Ther., 3, 797–813 (1989).PubMedCrossRefGoogle Scholar
  20. Tasaka K., Mitsunobu M., and Okamoto, M., Intracellular calcium release induced by histamine releasers and its inhibition by some antiallergic drugs.Annal. Allergy, 56, 464–469 (1986).Google Scholar

Copyright information

© The Pharmaceutical Society of Korea 2002

Authors and Affiliations

  • Eun-Kyung Park
    • 1
  • Min-Kyung Choo
    • 1
  • Hae-Kyung Yoon
    • 2
  • Dong-Hyun Kim
    • 1
  1. 1.College of PharmacyKyung Hee UniversitySeoulKorea
  2. 2.Department of Human Life ScienceKyungwon CollegeSongnam-cityKorea

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