Abstract
The seeds of Strophanthus kombé Oliv. are known to contain high levels of cardioactive compounds. However, the therapeutic use of Strophanthus in the treatment of cardiopathy requires more detailed knowledge of the compound profile to profit from the full potential of Strophanthus preparations. Therefore, the objective was to characterize the cardenolide profile and lipophilic constituents in S. kombé seeds using methods applicable in routine quality control. Freshly prepared S. kombé seed extracts were analyzed without previous sample clean-up using a novel HPLC-DAD-MSn method. In addition, seed oils were analyzed by GC-MS following derivatization of the lipids. More than 20 cardenolides were tentatively assigned in the seed extracts including strophanthidin, strophanthidol, periplogenin and strophanthidinic acid aglycones, carrying various saccharide moieties. The findings revealed the presence of eight novel cardenolides, which have not been described for S. kombé so far. The occurrence of strophanthidinic acid derivatives was verified by comparison with synthesized strophanthidinic acid-cymaropyranoside. GC-MS characterization of the oils mainly revealed the presence of fatty acids, especially oleic acid and linoleic acid, as well as phytosterols, the latter representing intermediates of cardenolide biosynthesis. In summary, these findings broaden our knowledge on the secondary metabolism of Strophanthus.
Dedicated to: Prof. Dr. habil. Dr. h.c. Reinhold Carle on the occasion of his 65th birthday.
Acknowledgments:
The authors are grateful to Prof. Dr. Otmar Spring (Hohenheim University, Stuttgart) for the taxonomy of plant specimens, and we wish to thank Dr. Ines Lederer (PhytoLab GmbH, Vestenbergsgreuth) for HR-MS analyses.
References
1. Beentje HJ. A monograph on Strophanthus DC. (Apocynaceae). PhD thesis. Netherlands: Wageningen University, 1982.Search in Google Scholar
2. Neuwinger HD. Afrikanische Arzneipflanzen und Jagdgifte, 2nd ed. Stuttgart: Wissenschaftliche Verlagsgesellschaft, 1998:142–5.Search in Google Scholar
3. Fraser TR. On the Kombé arrow-poison (Strophanthus Hispidus, DC) of Africa. J Anat Physiol 1872;7:139.Search in Google Scholar
4. Mijatovic T, Van Quaquebeke E, Delest B, Debeir O, Darro F, Kiss R. Cardiotonic steroids on the road to anti-cancer therapy. Biochim Biophys Acta 2007;1776:32–57.10.1016/j.bbcan.2007.06.002Search in Google Scholar
5. Newman RA, Yang P, Pawlus AD, Block KI. Cardiac glycosides as novel cancer therapeutic agents. Mol Interv 2008;8:36.10.1124/mi.8.1.8Search in Google Scholar
6. Krenn L, Svardal M, Kopp B. The Strophanthus species in Reichstein’s plant drug collection. Sci Pharm 1993;61:83–131.Search in Google Scholar
7. Mutschler E, Geisslinger G, Kroemer HK, Ruth P, Schäfer-Korting M. Arzneimittelwirkungen, Lehrbuch der Pharmakologie und Toxikologie, 9th ed. Stuttgart: Wissenschaftliche Verlagsgesellschaft, 2008:580–4.Search in Google Scholar
8. Corona GL, Raiteri M. Separation and quantitative determination of K-strophanthin glycosides by thin-layer chromatography. J Chromatogr 1965;19:435–7.Search in Google Scholar
9. Kartnig T, Danhofer R. Zur Identifizierung und quantitativen Analyse von Strophanthusglykosiden. J Chromatogr A 1970;52:313–20.10.1016/S0021-9673(01)96578-1Search in Google Scholar
10. Davydov VY, Kiselev AV, Mironova IV, Sapojnikov YM. Liquid chromatography of cardiac glycosides. Chromatographia 1978;11:591–5.10.1007/BF02268929Search in Google Scholar
11. Karch K, Sebestian I, Halász I, Engelhardt H. Optimization of reversed-phase separations. J Chromatogr A 1976;122:171–84.10.1016/S0021-9673(00)82243-8Search in Google Scholar
12. Tittel G, Habermeier H, Wagner H. Qualitative and quantitative HPLC-analysis of cardiac glycosides. Planta Med 1982;45:207–15.10.1055/s-2007-971375Search in Google Scholar
13. Brown P, Brüschweiler F, Pettit GR. Field ionization mass spectrometry – III. Org Mass Spectrom 1971;5:573–97.10.1002/oms.1210050509Search in Google Scholar
14. Tracqui A, Kintz P, Ludes B, Mangin P. High-performance liquid chromatography-ionspray mass spectrometry for the specific determination of digoxin and some related cardiac glycosides in human plasma. J Chromatogr B 1997;692: 101–9.10.1016/S0378-4347(96)00462-8Search in Google Scholar
15. Filigenzi MA, Woods LW, Booth MC, Tor ER, Puschner B. Determination of strophanthidin in ingesta and plant material by LC-MS/MS. J Agric Food Chem 2004;52:2174–8.10.1021/jf035443bSearch in Google Scholar PubMed
16. Grosa G, Allegrone G, Del Grosso E. LC-ESI-MS/MS characterization of strophanthin-K. J Pharm Biomed Anal 2005;38:79–86.10.1016/j.jpba.2004.12.008Search in Google Scholar PubMed
17. Gunstone FD, Qureshi MI. Glyceride studies. VIII. The component glycerides of four Strophanthus oils containing an unsaturated hydroxy acid. J Sci Food Agric 1968;19:386–8.10.1002/jsfa.2740190708Search in Google Scholar
18. GHP, German Homoeopathic Pharmacopoeia, H 5.4.4 Special Manufacturing Regulations. Regulation No. 33–37. Stuttgart/Eschborn: Deutscher Apotheker Verlag, 2012.Search in Google Scholar
19. Lorenz P, Conrad J, Stintzing FC. Metabolic fate of depsides and alkaloid constituents in aqueous extracts from Mercurialis perennis L. during fermentation. Chem Biodivers 2013;10: 1706–23.10.1002/cbdv.201200424Search in Google Scholar
20. Butte W. Rapid method for the determination of fatty acid profiles from fats and oils using trimethylsulphonium hydroxide for transesterification. J Chromatogr A 1983;261:142–5.10.1016/S0021-9673(01)87931-0Search in Google Scholar
21. Jacobs WA. Strophanthidin III. Crystalline kombé strophanthidin – Preliminary note. J Biol Chem 1923;57: 569–72.10.1016/S0021-9258(18)85518-1Search in Google Scholar
22. Makarevich IF. Cardenolides of Strophanthus kombé. II. Chem Nat Comp 1972;8:184–90.10.1007/BF00565297Search in Google Scholar
23. Lorenz P, Knödler M, Bertrams J, Berger M, Meyer U, Stintzing FC. n-Alkylresorcinol occurrence in Mercurialis perennis L. (Euphorbiaceae). Z Naturforsch C 2010;65:174–9.10.1515/znc-2010-3-402Search in Google Scholar PubMed
24. Tittel G. Substitution of animal tests in pharmacy. Use of HPLC instead of the German pharmacopeial guinea pig test for the determination of cardiac glycosides and of drugs obtained from plants. Pharm Ind 1986;48:822–36.Search in Google Scholar
25. Knittel DN, Stintzing FC, Kammerer DR. Simultaneous determination of bufadienolides and phenolic compounds in sea squill (Drimia maritima (L.) Stearn) by HPLC-DAD-MSn as a means to differentiate individual plant parts and developmental stages. Anal Bioanal Chem 2014;406:6035–50.10.1007/s00216-014-8008-0Search in Google Scholar PubMed
26. Zuo WJ, Dong WH, Zhao YX, Chen HQ, Mei WL, Dai HF. Two new strophanthidol cardenolides from the seeds of Antiaris toxicaria. Phytochem Lett 2013;6:1–4.10.1016/j.phytol.2012.10.001Search in Google Scholar
27. Makarevich IF. Cardiac glycosides of Cheiranthus allioni. VII. Chem Nat Comp 1972;8:191–5.10.1007/BF00565298Search in Google Scholar
28. Kubo S, Uroda M, Atsuo Y, Asatani D, Akagami H, Imaki Y. New cardenolides from the seeds of Adonis aestivalis. Chem Pharm Bull 2012;60:1275–82.10.1248/cpb.c12-00489Search in Google Scholar PubMed
29. Kaiser F, Haack E, Gube M, Dölberg U, Spingler H. Neue Glykoside aus den Samen von Strophanthus kombé. Naturwissenschaften 1959;46:670.10.1007/BF00594818Search in Google Scholar
30. Makarevich IF. 3-Epistrophanthidin and 3-epistrophanthidol. Chem Nat Comp 1969;5:427–30.10.1007/BF00568582Search in Google Scholar
31. Lichti H, Tamm C, Reichstein T. Die Glykoside der Samen von Strophanthus Ledienii Stein. 2. Mitteilung. Glykoside und Aglykone, 166. Mitteilung. Helv Chim Acta 1956;39:1914–32.10.1002/hlca.19560390706Search in Google Scholar
32. Jacobs WA, Hoffmann A, Strophanthidin X. On k-strophanthin-β and other kombé strophanthins. J Biol Chem 1926;69:153–63.10.1016/S0021-9258(18)84601-4Search in Google Scholar
33. Keller L, Tamm C. Die Glykoside der Samen von Strophanthus hispidus P. DC. 2. Mitteilung. Glykoside und Aglykone, 209. Mitteilung. Helv Chim Acta 1959;42:2467–85.10.1002/hlca.19590420719Search in Google Scholar
34. Zelnik R, Schindler O, Reichstein T. Die Glykoside der Samen von Strophanthus kombé. Helv Chim Acta 1960;43:593–4.10.1002/hlca.19600430219Search in Google Scholar
35. Jacobs WA, Hoffmann A. Periplocymarin and periplogenin. J Biol Chem 1928;79:519–30.10.1016/S0021-9258(20)79943-6Search in Google Scholar
36. Von Euw J, Reichstein T. Die Glykoside der Samen von Strophanthus Nicholsonii Holm. Glykoside und Aglykone. 34. Mitteilung. Helv Chim Acta 1948;31:883–92.10.1002/hlca.19480310330Search in Google Scholar
37. Jacobs WA, Hoffmann A. Strophanthidin IX. On crystalline kombé Strophanthidin. J Biol Chem 1926;67:609–20.10.1016/S0021-9258(18)84696-8Search in Google Scholar
38. Li Y, Wu X, Li J, Wang Y, Yu S, Lv H, et al. Identification of cardiac glycosides in fractions from Periploca forrestii by high-performance liquid chromatography/diode-array detection/electrospray ionization multi-stage tandem mass spectrometry and liquid chromatography/nuclear magnetic resonance. J Chromatogr B 2010;878:381–90.10.1016/j.jchromb.2009.12.008Search in Google Scholar PubMed
39. Makarevich IF, Kovganko NV. Cardiac glycosides from Strophanthus kombé. Chem Nat Comp 2006;42:189–93.10.1007/s10600-006-0075-9Search in Google Scholar
40. Rashan LJ, Franke K, Khine MM, Kelter G, Fiebig HH, Neumann J, et al. Characterization of the anticancer properties of monoglycosidic cardenolides isolated from Nerium oleander and Streptocaulon tomentosum. J Ethnopharm 2011;134:781–8.10.1016/j.jep.2011.01.038Search in Google Scholar PubMed
41. Makarevich IF, Kovganko NV, Gubin IY, Zhernoklev KV, Slyusarskaya TV, Yarmolenko GN. Cardenolides of Strophanthus kombé III. 17-alpha Strophadogenin. Chem Nat Comp 1993;29:642–6.10.1007/BF00630215Search in Google Scholar
42. Kreis W, Müller-Uri F. Biochemistry of sterols, cardiac glycosides, brassinosteroids, phytoecdysteroids and steroid saponins. Annu Plant Rev Vol. 40. In: Biochemistry of Plant Secondary Metabolism, 2010:304–63.10.1002/9781444320503.ch6Search in Google Scholar
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