Journal of Natural Medicines

, Volume 68, Issue 3, pp 561–566 | Cite as

Acylated phenylethanoid glycosides, echinacoside and acteoside from Cistanche tubulosa, improve glucose tolerance in mice

  • Toshio Morikawa
  • Kiyofumi Ninomiya
  • Mio Imamura
  • Junji Akaki
  • Shota Fujikura
  • Yingni Pan
  • Dan Yuan
  • Masayuki Yoshikawa
  • Xiaoguang Jia
  • Zheng Li
  • Osamu Muraoka
Original Paper

Abstract

Acylated phenylethanoid glycosides, echinacoside (1) and acteoside (2), principal constituents in stems of Cistanche tubulosa (Orobanchaceae), inhibited the increase in postprandial blood glucose levels in starch-loaded mice at doses of 250–500 mg/kg p.o. These compounds (1 and 2) also significantly improved glucose tolerance in starch-loaded mice after 2 weeks of continuous administration at doses of 125 and/or 250 mg/kg/day p.o. without producing significant changes in body weight or food intake. In addition, several constituents from C. tubulosa, including 1 (IC50 = 3.1 μM), 2 (1.2 μM), isoacteoside (3, 4.6 μM), 2′-acetylacteoside (4, 0.071 μM), tubulosides A (5, 8.8 μM) and B (9, 4.0 μM), syringalide A 3-O-α-l-rhamnopyranoside (10, 1.1 μM), campneoside I (13, 0.53 μM), and kankanoside J1 (14, 9.3 μM), demonstrated potent rat lens aldose reductase inhibitory activity. In particular, the potency of compound 4 was similar to that of epalrestat (0.072 μM), a clinical aldose reductase inhibitor.

Keywords

Echinacoside Acteoside Glucose tolerance improvement effect Aldose reductase inhibitor Cistanche tubulosa 

Notes

Acknowledgments

This work was supported in part by a Grant-in Aid for Scientific Research by Japan Society for the Promotion of Science (JSPS) KAKENHI a Grant Number 24590153 and The Japan–China Medical Association for the financial support.

References

  1. 1.
    Jiménez C, Riguera R (1994) Phenylethanoid glycosides in plants: structure and biological activity. Nat Prod Rep 11:591–606PubMedCrossRefGoogle Scholar
  2. 2.
    Fu G, Pang H, Wong YH (2008) Naturally occurring phenylethanoid glycosides: potential leads for new therapeutics. Curr Med Chem 15:2592–2613PubMedCrossRefGoogle Scholar
  3. 3.
    He J, Hu X-P, Zeng Y, Li Y, Wu H-Q, Qiu R-Z, Ma W-J, Li T, Li C-Y, He Z-D (2011) Advanced research on acteoside for chemistry and bioactivities. J Asian Nat Prod Res 13:449–464PubMedCrossRefGoogle Scholar
  4. 4.
    Stoll A, Renz J, Brack A (1950) Isolierung und konstitution des echinacosids, eines glykosids aus den wurzeln von Echinacea angustifolia D. C. 6. mitteilung über antibakterielle stoffe. Helv Chim Acta 33:1877–1893CrossRefGoogle Scholar
  5. 5.
    Becker H, Hsieh WC, Wylde R, Laffite C, Andary C (1982) Structure of echinacoside. Z Naturforsch C: Biosci 37C:351–353Google Scholar
  6. 6.
    Scarpati ML, Dell MF (1963) Isolation from Verbascum sinuatum of two new glucosides, verbascoside and isoverbascoside. Ann Chim 53:356–367Google Scholar
  7. 7.
    Birkofer L, Kaiser C, Thomas U (1968) Sugar esters. IV. acteoside and neoacteoside, sugar esters from Syringa vulgaris. Z Naturforsch, B: Chem Sci 23:1051–1058Google Scholar
  8. 8.
    Andary C, Wylde R, Laffite C, Privat G, Winternitz F (1982) Structures of varbascoside and orobanchoside, caffeic acid sugar esters from Orobanche rapum-genistae. Phytochemistry 21:1123–1127CrossRefGoogle Scholar
  9. 9.
    Sakurai A, Kato T (1983) A new glycoside, kusaginin isolated from Clerodendron trichotomum. Bull Chem Soc Jpn 56:1573–1574CrossRefGoogle Scholar
  10. 10.
    Lee KJ, Woo E-R, Choi CY, Shin DW, Lee DG, You HJ, Jeong HG (2004) Protective effect of acteoside on carbon tetrachloride-induced hepatotoxicity. Life Sci 74:1051–1064PubMedCrossRefGoogle Scholar
  11. 11.
    Jia C, Shi H, Jin W, Zhang K, Jiang Y, Zhao M, Tu P (2009) Metabolism of echinacoside, a good antioxidant, in rats: isolation and identification of its biliary metabolites. Drug Metab Dispos 37:431–438PubMedCrossRefGoogle Scholar
  12. 12.
    Jia Y, Guan Q, Guo Y, Du C (2012) Echinacoside stimulates cell proliferation and prevents cell apoptosis in intestinal epithelial MODE-K cells by up-regulation of transforming growth factor-β1 expression. J Pharmacol Sci 118:99–108PubMedCrossRefGoogle Scholar
  13. 13.
    Li F, Yang Y, Zhu P, Chen W, Qi D, Shi X, Zhang C, Yang Z, Li P (2012) Echinacoside promotes bone regeneration by increasing OPG/RANKL ratio in MC3T3-E1 cells. Fitoterapia 83:1443–1450PubMedCrossRefGoogle Scholar
  14. 14.
    Li F, Yang X, Yang Y, Guo C, Zhang C, Yang Z, Li P (2013) Antiosteoporotic activity of echinacoside in ovariectomized rats. Phytomedicine 20:549–557PubMedCrossRefGoogle Scholar
  15. 15.
    Yoshikawa M, Matsuda H, Morikawa T, Xie H, Nakamura S, Muraoka O (2006) Phenylethanoid oligoglycosides and acylated oligosugars with vasorelaxant activity from Cistanche tubulosa. Bioorg Med Chem 14:7468–7475PubMedCrossRefGoogle Scholar
  16. 16.
    Morikawa T, Pan Y, Ninomiya K, Imura K, Matsuda H, Yoshikawa M, Yuan D, Muraoka O (2010) Acylated phenylethanoid oligoglycosides with hepatoprotective activity from the desert plant Cistanche tubulosa. Bioorg Med Chem 18:1882–1890PubMedCrossRefGoogle Scholar
  17. 17.
    Pan Y, Morikawa T, Ninomiya K, Imura K, Yuan D, Yoshikawa M, Muraoka O (2010) Bioactive constituents from Chinese natural medicines. XXXVI. Four new acylated phenylethanoid oligoglycosides, kankanosides J1, J2, K1, and K2, from stems of Cistanche tubulosa. Chem Pharm Bull 58:575–578PubMedCrossRefGoogle Scholar
  18. 18.
    Xie H, Morikawa T, Matsuda H, Nakamura S, Muraoka O, Yoshikawa M (2006) Monoterpene constituents from Cistanche tubulosa: chemical structures of kankanosides A-E and kankanol. Chem Pharm Bull 54:669–675PubMedCrossRefGoogle Scholar
  19. 19.
    Morikawa T, Pan Y, Ninomiya K, Imura K, Yuan D, Yoshikawa M, Hayakawa T, Muraoka O (2010) Iridoid and acyclic monoterpene glycosides, kankanosides L, M, N, O, and P from Cistanche tubulosa. Chem Pharm Bull 58:1403–1407PubMedCrossRefGoogle Scholar
  20. 20.
    Kobayashi H, Oguchi H, Takizawa N, Miyase T, Ueno A, Usmanghani K, Ahmad M (1987) New phenylethanoid glycosides from Cistanche tubulosa (Schrenk) Hook. f. I. Chem Pharm Bull 35:3309–3314CrossRefGoogle Scholar
  21. 21.
    Shimoda H, Tanaka J, Takahara Y, Takemoto K, Shan S-J, Su M-H (2009) The hypocholesterolemic effects of Cistanche tubulosa extract, a Chinese traditional crude medicine, in mice. Am J Chin Med 37:1125–1138PubMedCrossRefGoogle Scholar
  22. 22.
    Yoshikawa M, Morikwa T, Matsuda H, Tanabe G, Muraoka O (2002) Absolute stereostructure of potent α-glucosidase inhibitor, salacinol, with unique thiosugar sulfonium sulfate inner salt structure from salacia reticulata. Bioorg Med Chem 10:1547–1554PubMedCrossRefGoogle Scholar
  23. 23.
    Muraoka O, Morikawa T, Miyake S, Akaki J, Ninomiya K, Yoshikawa M (2010) Quantitative determination of potent α-glucosidase inhibitors, salacinol and kotalanol, in Salasia species using liquid chromatography-mass spectrometry. J Pharm Biomed Anal 52:770–773PubMedCrossRefGoogle Scholar
  24. 24.
    Muraoka O, Morikawa T, Miyake S, Akaki J, Ninomiya K, Pongpiriyadacha Y, Yoshikawa M (2011) Quantitative analysis of neosalacinol and neokotalanol, another two potent α-glucosidase inhibitors from Salacia species, by LC-MS with ion pair chromatography. J Nat Med 65:142–148PubMedCrossRefGoogle Scholar
  25. 25.
    Matsuda H, Morikawa T, Toguchida I, Yoshikawa M (2002) Structural requirements of flavonoids and related compounds for aldose reductase inhibitory activity. Chem Pharm Bull 50:788–795PubMedCrossRefGoogle Scholar
  26. 26.
    Yoshikawa M, Morikawa T, Murakami T, Toguchida I, Harima S, Matsuda H (1999) Medicinal flowers. I. aldose reductase inhibitors and three new eudesmane-type sesquiterpenes, kikkanols A, B, and C, from the flowers of Chrysanthemum indicum L. Chem Pharm Bull 47:340–345PubMedCrossRefGoogle Scholar
  27. 27.
    Matsuda H, Morikawa T, Toguchida I, Harima S, Yoshikawa M (2002) Medicinal flowers. VI. Absolute stereostructures of two new flavanone glycosides and a phenylbutanoid glycoside from the flowers of Chrysanthemum indicum L.: their inhibitory activities for rat lens aldose reductase. Chem Pharm Bull 50:972–975PubMedCrossRefGoogle Scholar
  28. 28.
    Yoshikawa M, Murakami T, Ishiwada T, Morikawa T, Kagawa M, Higashi Y, Matsuda H (2002) New flavonol oligoglycosides and polyacylated sucroses with inhibitory effects on aldose reductase and platelet aggregation from the flowers of Prunus mume. J Nat Prod 65:1151–1155PubMedCrossRefGoogle Scholar
  29. 29.
    Matsuda H, Morikawa T, Yoshikawa M (2002) Antidiabetogenic constituents from several natural medicines. Pure Appl Chem 74:1301–1308CrossRefGoogle Scholar
  30. 30.
    Xie H, Wang T, Matsuda H, Morikawa T, Yoshikawa M, Tani T (2005) Bioactive constituents from Chinese natural medicines. XV. Inhibitory effect on aldose reductase and structures of saussureosides A and B from Saussurea medusa. Chem Pharm Bull 53:1416–1422PubMedCrossRefGoogle Scholar
  31. 31.
    Morikawa T, Xie H, Wang T, Matsuda H, Yoshikawa M (2008) Bioactive constituents from Chinese natural medicines. XXXII. Aminopeptidase N and aldose reductase inhibitors from Sinocrassula indica: structures of sinocrassosides B4, B5, C1, and D1–D3. Chem Pharm Bull 56:1438–1444PubMedCrossRefGoogle Scholar
  32. 32.
    Morikawa T, Chaipech S, Matsuda H, Hamao M, Umeda Y, Sato H, Tamura H, Kon’i H, Ninomiya K, Yoshikawa M, Pongpiriyadacha Y, Hayakawa T, Muraoka O (2012) Antidiabetogenic oligostilbenoids and 3-ethyl-4-phenyl-3,4-dihydroisocoumarins from the bark of Shorea roxburghii. Bioorg Med Chem 20:832–840PubMedCrossRefGoogle Scholar
  33. 33.
    Morikawa T, Kishi A, Pongiriyadacha Y, Matusda H, Yoshikawa M (2003) Structures of new friedelane-type triterpenes and eudesmane-type sesquiterpene and aldose reductase inhibitors from Salacia chinensis. J Nat Prod 66:1191–1196PubMedCrossRefGoogle Scholar

Copyright information

© The Japanese Society of Pharmacognosy and Springer Japan 2014

Authors and Affiliations

  • Toshio Morikawa
    • 1
    • 2
  • Kiyofumi Ninomiya
    • 1
    • 2
  • Mio Imamura
    • 1
  • Junji Akaki
    • 1
  • Shota Fujikura
    • 1
  • Yingni Pan
    • 1
    • 3
  • Dan Yuan
    • 3
  • Masayuki Yoshikawa
    • 1
  • Xiaoguang Jia
    • 4
  • Zheng Li
    • 5
  • Osamu Muraoka
    • 1
    • 2
  1. 1.Pharmaceutical Research and Technology InstituteKinki UniversityOsakaJapan
  2. 2.Antiaging CentreKinki UniversityOsakaJapan
  3. 3.School of Traditional Chinese MedicinesShenyang Pharmaceutical UniversityShenyangPeople’s Republic of China
  4. 4.Xinjiang Institute of Chinese Materia Medica and EthnodrugÜrümqiPeople’s Republic of China
  5. 5.Eishin Trading Co., Ltd.OsakaJapan

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