Advertisement

Journal of Natural Medicines

, Volume 71, Issue 4, pp 780–790 | Cite as

Nine pairs of megastigmane enantiomers from the leaves of Eucommia ulmoides Oliver

  • Jiankun Yan
  • Xuliu Shi
  • Paul Owusu Donkor
  • Huajie Zhu
  • Xiumei Gao
  • Liqin Ding
  • Feng Qiu
Note

Abstract

Nine pairs of megastigmane enantiomers (1a/1b9a/9b), comprising two new compounds (6S,9R)-blumenol C (7b), (6S,9S)-blumenol C (8b), two pairs of enantiomers (+)-(6R)-eucomegastigmane A (1a), (−)-(6S)-eucomegastigmane A (1b), (+)-(3S,4S)-eucomegastigmane B (5a), (−)-(3R,4R)-eucomegastigmane B (5b) isolated by chiral resolution firstly, and twelve known compounds, were isolated from the leaves of Eucommia ulmoides Oliver. Their structures were elucidated based on extensive spectroscopic analysis. Absolute configurations of the megastigmane enantiomers were assigned by comparing experimental ECD and OR with calculated ECD and OR. Docking-based virtual screening of all compounds showed that megastigmane enantiomers have weak intermolecular interactions with the binding site residues of angiotensin-converting enzyme (ACE) and angiotensin II type 1 receptor (AT1R).

Keywords

Leaves of Eucommia ulmoides Oliver Megastigmane enantiomers ECD OR Absolute configuration Virtual screening CDOCKER 

Notes

Acknowledgements

This work was supported by grants from the State Key Program of National Natural Science of China (no. 81430095) and the National Natural Science Foundation of China (no. 81303180).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supporting information

Additional supporting information may be found in the online version of this article at the publisher’s website.

Supplementary material

11418_2017_1102_MOESM1_ESM.doc (12.8 mb)
Supplementary material 1 (DOC 13107 kb)

References

  1. 1.
    Yamaguchi Y, Kawamura N, Tsuboi T, Yamaguchi Y, Hirata T, Ueda T, Tagawa C, Nakazawa Y, Onizuka S, Tagashira E, Nishibe S (2007) Effect of the Eucommia ulmoides leaf extract on blood pressure. In: Proceedings of the international symposium on Eucommia ulmoides, pp 55–62Google Scholar
  2. 2.
    Tagawa C, Nakazawa Y, Tagashira E, Ueda T, Yamaguchi Y, Ohara T, Onizuka S, Nishibe S (2005) Effect of Eucommia leaf (Eucommia ulmoides Oliver; Du-Zhong yge) extract on blood pressure (2). Nat Med 59:117–120Google Scholar
  3. 3.
    Nakazawa Y, Odagiri N, Imai R, Yoshii T, Tagashira E, Nakata C, Nakamura T, Asaumi M, Onizuka S, Yahara M (1997) Effect of Eucommia leaf (Eucommia ulmoides Oliver leaf; Du-Zhong yge) extract on blood pressure (I): effect on blood pressure in spontaneous hypertensive rats (SHR). Nat Med 51:392–398Google Scholar
  4. 4.
    Hirata T, Kobayashi T, Wada A, Ueda T, Fujikawa T, Miyashita H, Ikeda T, Tsukamoto S, Nohara T (2011) Anti-obesity compounds in green leaves of Eucommia ulmoides. Bioorg Med Chem Lett 21:1786–1791CrossRefPubMedGoogle Scholar
  5. 5.
    Bai MM, Shi W, Tian JM, Lei M, Kim JH, Sun YN, Kim YH, Gao JM (2015) Soluble epoxide hydrolase inhibitory and anti-inflammatory components from the leaves of Eucommia ulmoides Oliver (Duzhong). J Agric Food Chem 63:2198–2205CrossRefPubMedGoogle Scholar
  6. 6.
    Takamura C, Hirata T, Ueda T, Ono M, Miyashita H, Ikeda T, Nohara T (2007) Iridoids from the green leaves of Eucommia ulmoides. J Nat Prod 70:1312–1316CrossRefPubMedGoogle Scholar
  7. 7.
    Hattori M, Che QM, Gewali MB, Nomura Y, Tezuka Y, Kikuchi T, Namba T (1988) Studies on Du-Zhong leaves (III): constituents of the leaves of Eucommia ulmoides (1). Jpn J Pharmacogn 42:76–80Google Scholar
  8. 8.
    Bianco A, Bonini C, Guiso M, Iavarone C, Trogolo C (1978) Iridoids. XXVI. Ulmoside (aucubigenin 1 beta isomaltoside), a new iridoid from Eucommia ulmoides. Gaz Chim ItalGoogle Scholar
  9. 9.
    Nakamura T, Nakazawa Y, Onizuka S, Tanaka C, Yahara S, Nohara T (1997) Studies on the constituents of Eucommia ulmoides iridoids from the leaves. Nat Med 51:275–277Google Scholar
  10. 10.
    Bianco A, Iavarone C, Trogolo C (1974) Structure of eucommiol, a new cyclopentenoid-tetrol from Eucommia ulmoides. Tetrahedron 30:4117–4121CrossRefGoogle Scholar
  11. 11.
    Bianco A, Bonini CC, Iavarone C, Trogolo C (1982) Structure elucidation of eucommioside (2″-O-β-d-glucopyranosyl eucommiol) from Eucommia ulmoides. Phytochemistry 21:201–203CrossRefGoogle Scholar
  12. 12.
    Shimoyama A, Yamadaki M, Nakazawa Y, Yahara S, Nohara T (1993) Studies on the constituents of the leaves of Eucommia ulmoides. Jpn J Pharmacogn 47:56–59Google Scholar
  13. 13.
    Young HS, Park JC, Park HJ, Lee JH, Choi JS (1991) Phenolic compounds of the leaves of Eucommia ulmoides. Arch Pharmacal Res 14:114–117CrossRefGoogle Scholar
  14. 14.
    Nakamura T, Nakazawa Y, Onizuka S, Tanaka C, Yahara S, Nohara T (1998) Twelve phenolics from leaves of Eucommia ulmoides. Nat Med 52:460Google Scholar
  15. 15.
    Takamura C, Hirata T, Yamaguchi Y, Ono M, Miyashita H, Ikeda T, Nohara T (2007) Studies on the chemical constituents of green leaves of Eucommia ulmoides Oliv. J Nat Med 61:220–221CrossRefGoogle Scholar
  16. 16.
    Kim HY, Moon BH, Lee HJ, Choi DH (2004) Flavonol glycosides from the leaves of Eucommia ulmoides O. with glycation inhibitory activity. J Ethnopharmacol 93:227–230CrossRefPubMedGoogle Scholar
  17. 17.
    Li C, Li L, Wang C, Yang J, Ye F, Tian J, Si Y, Zhang D (2012) A new ursane-type nor-triterpenoid from the leaves of Eucommia ulmoides Oliv. Molecules 17:13960–13968CrossRefPubMedGoogle Scholar
  18. 18.
    Tanaka C, Nakamura T, Nakazawa Y, Nohara T (1997) A new triterpenoid from the leaves of Eucommia ulmoides OLIV. Chem Pharm Bull 45:1379–1380CrossRefGoogle Scholar
  19. 19.
    Zuo YM, Cai MT, Zhang ZL, Liu RH, Chen LY (2014) Study on chemical constituents of Eucommia ulmoides leaves. J Chin Med Mater 37:1786–1788Google Scholar
  20. 20.
    Tran TH, Le Huyen T, Tran TM, Nguyen TA, Pham TB, Nguyen Tien D (2016) A new megastigmane sulphoglycoside and polyphenolic constituents from pericarps of Garcinia mangostana. Nat Prod Res 30:1598–1604CrossRefPubMedGoogle Scholar
  21. 21.
    Uemura Y, Iwami M, Kawakami S, Sugimoto S, Matsunami K, Otsuka H, Shinzato T, Kawahata M, Yamaguchi K (2015) Megastigmane glucosides and megastigmanes from the leaves of Meliosma lepidota ssp. squamulata. Chem Pharm Bull 63:608–616CrossRefPubMedGoogle Scholar
  22. 22.
    Kawakami S, Matsunami K, Otsuka H, Shinzato T, Takeda Y (2011) Crotonionosides A–G: megastigmane glycosides from leaves of Croton cascarilloides Räuschel. Phytochemistry 72:147–153CrossRefPubMedGoogle Scholar
  23. 23.
    Zhang Z, Zhang W, Ji Y-P, Zhao Y, Wang C-G, Hu J-F (2010) Gynostemosides A–E, megastigmane glycosides from Gynostemma pentaphyllum. Phytochemistry 71:693–700CrossRefPubMedGoogle Scholar
  24. 24.
    Zhang Y, Nakamura S, Pongpiriyadacha Y, Matsuda H, Yoshikawa M (2008) Absolute structures of new megastigmane glycosides, foliasalaciosides E(1), E(2), E(3), F, G, H, and I from the leaves of Salacia chinensis. Chem Pharm Bull 56:547–553CrossRefPubMedGoogle Scholar
  25. 25.
    Almeida MDFO, Melo ACRD, Pinheiro MLB, Silva JRDA, Souza ADLD, Barison A, Campos FR, Amaral ACF, Machado GMDC, Leon LLP (2011) Chemical constituents and Leishmanicidal activity of Gustavia elliptica (Lecythidaceae). Quim Nova 34:1182–1187CrossRefGoogle Scholar
  26. 26.
    Shitamoto J, Sugimoto S, Matsunami K, Otsuka H, Shinzato T, Takeda Y (2011) Tricalysionoside A, a megastigmane gentiobioside, sulfatricalysines A–F, and tricalysiosides X–Z, ent-kaurane glucosides, from the leaves of Tricalysia dubia. Chem Pharm Bull 59:72–77CrossRefPubMedGoogle Scholar
  27. 27.
    Yamano Y, Ito M (2005) Synthesis of optically active vomifoliol and roseoside stereoisomers. Chem Pharm Bull 53:541–546CrossRefPubMedGoogle Scholar
  28. 28.
    Pabst A, Barron D, Sémon E, Schreier P (1992) Two diastereomeric 3-oxo-α-ionol β-d-glucosides from raspberry fruit. Phytochemistry 31:1649–1652CrossRefGoogle Scholar
  29. 29.
    Baumes RL, Aubert CC, Günata ZY, De Moor W, Bayonove CL, Tapiero C (1994) Structures of two C13-norisoprenoid glucosidic precursors of wine flavor. J Essent Oil Res 6:587–599CrossRefGoogle Scholar
  30. 30.
    Matsunami K, Otsuka H, Takeda Y (2010) Structural revisions of blumenol C glucoside and byzantionoside B. Chem Pharm Bull 58:438–441CrossRefPubMedGoogle Scholar
  31. 31.
    Ito N, Etoh T, Hagiwara H, Kato M (1997) Novel synthesis of degradation products of carotenoids, megastigmatrienone analogues and blumenol-A. J Chem Soc Perkin Trans 1:1571–1580. doi: 10.1039/A607028K CrossRefGoogle Scholar
  32. 32.
    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 53:1416–1422CrossRefPubMedGoogle Scholar
  33. 33.
    Shimizu S, Miyase T, Ueno A, Usmanghani K (1989) Sesquiterpene lactone glycosides and ionone derivative glycosides from Sonchus asper. Phytochemistry 28:3399–3402CrossRefGoogle Scholar
  34. 34.
    Buschor DJ, Eugster CH (1990) Synthese der (3S, 4R, 3′S, 4′R)- und (3S, 4S, 3′S, 4′S) crustaxanthine sowie weiterer verbindungen mit 3,4-Dihydroxy-β-Endgruppen. Helv Chim Acta 73:1002–1021CrossRefGoogle Scholar
  35. 35.
    Takeda Y, Zhang H, Masuda T, Honda G, Otsuka H, Sezik E, Yesilada E, Sun H (1997) Megastigmane glucosides from Stachys byzantina. Phytochemistry 44:1335–1337CrossRefGoogle Scholar
  36. 36.
    Natesh R, Schwager SL, Sturrock ED, Acharya KR (2003) Crystal structure of the human angiotensin-converting enzyme–lisinopril complex. Nature 421:551–554CrossRefPubMedGoogle Scholar
  37. 37.
    Zhang H, Unal H, Gati C, Han GW, Liu W, Zatsepin NA, James D, Wang D, Nelson G, Weierstall U, Sawaya MR (2015) Structure of the angiotensin receptor revealed by serial femtosecond crystallography. Cell 161:833–844CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Actis-Goretta L, Ottaviani JI, Fraga CG (2006) Inhibition of angiotensin converting enzyme activity by flavanol-rich foods. J Agric Food Chem 54:229–234CrossRefPubMedGoogle Scholar
  39. 39.
    Guerrero L, Castillo J, Quiñones M, Garcia-Vallvé S, Arola L, Pujadas G, Muguerza B (2012) Inhibition of angiotensin-converting enzyme activity by flavonoids: structure–activity relationship studies. PLoS One 7:e49493CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Parellada J, Suárez G, Guinea M (1998) Inhibition of zinc metallopeptidases by flavonoids and related phenolic compounds: structure–activity relationships. J Enzym Inhib 13:347–359CrossRefPubMedGoogle Scholar
  41. 41.
    Edwards RL, Lyon T, Litwin SE, Rabovsky A, Symons JD, Jalili T (2007) Quercetin reduces blood pressure in hypertensive subjects. J Nutr 137:2405–2411CrossRefPubMedGoogle Scholar
  42. 42.
    Larson AJ, Symons JD, Jalili T (2010) Quercetin: a treatment for hypertension?—a review of efficacy and mechanisms. Pharmaceuticals 3:237–250CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Mackraj I, Govender T, Ramesar S (2008) The antihypertensive effects of quercetin in a salt-sensitive model of hypertension. J Cardiovasc Pharmacol 51:239–245CrossRefPubMedGoogle Scholar
  44. 44.
    Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Scalmani G, Barone V, Mennucci B, Petersson GA, Nakatsuji H, Caricato M, Li X, Hratchian HP, Izmaylov AF, Bloino J, Zheng G, Sonnenberg JL, Hada M, Ehara M, Toyota K, Fukuda R, Hasegawa J, Ishida M, Nakajima T, Honda Y, Kitao O, Nakai H, Vreven T, Montgomery Jr. JA, Peralta JE, Ogliaro F, Bearpark MJ, Heyd J, Brothers EN, Kudin KN, Staroverov VN, Kobayashi R, Normand J, Raghavachari K, Rendell AP, Burant JC, Iyengar SS, Tomasi J, Cossi M, Rega N, Millam NJ, Klene M, Knox JE, Cross JB, Bakken V, Adamo C, Jaramillo J, Gomperts R, Stratmann RE, Yazyev O, Austin AJ, Cammi R, Pomelli C, Ochterski JW, Martin RL, Morokuma K, Zakrzewski VG, Voth GA, Salvador P, Dannenberg JJ, Dapprich S, Daniels AD, Farkas Ö, Foresman JB, Ortiz JV, Cioslowski J, Fox DJ (2009) Gaussian 09. In: Gaussian, Inc., Wallingford, CT, USAGoogle Scholar
  45. 45.
    Stephens PJ, Devlin FJ, Cheeseman JR, Frisch MJ, Rosini C (2002) Determination of absolute configuration using optical rotation calculated using density functional theory. Org Lett 4:4595–4598CrossRefPubMedGoogle Scholar
  46. 46.
    Pan JJ (2007) Studies of chiral molecules using chiroptical spectroscopies. PhD thesis, University of Southern California, Los Angeles, CA, 655 ppGoogle Scholar
  47. 47.
    Pescitelli G, Bruhn T (2016) Good computational practice in the assignment of absolute configurations by TDDFT calculations of ECD spectra. Chirality 28:466–474CrossRefPubMedGoogle Scholar
  48. 48.
    Bruhn T, Schaumlöffel A, Hemberger Y, Bringmann G (2013) SpecDis: quantifying the comparison of calculated and experimental electronic circular dichroism spectra. Chirality 25:243–249CrossRefPubMedGoogle Scholar

Copyright information

© The Japanese Society of Pharmacognosy and Springer Japan KK 2017

Authors and Affiliations

  1. 1.School of Chinese Materia MedicaTianjin University of Traditional Chinese MedicineTianjinPeople’s Republic of China
  2. 2.Tianjin State Key Laboratory of Modern Chinese MedicineTianjin University of Traditional Chinese MedicineTianjinPeople’s Republic of China
  3. 3.Department of Natural Products Chemistry, School of Traditional Chinese Materia Medica, Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of EducationShenyang Pharmaceutical UniversityShenyangPeople’s Republic of China
  4. 4.College of PharmacyHebei UniversityBaodingPeople’s Republic of China

Personalised recommendations