An in-depth look into a well-known herbal drug: Fingerprinting, isolation, identification, and content estimation of saponins in different Strophanthus seeds

Abstract

Seeds of Strophanthus species are known as a source of rapid-acting cardenolides. These water-soluble glycosides are listed as the sole critical constituents of this raw herbal drug. A non-standard cardioprotective medication with ouabain-containing oral remedies has become popular in Europe as a result of the withdrawal of corresponding registered drugs from the market. However, the bioequivalence of pure ouabain solutions, tinctures, and home-made extracts from Strophanthus seeds is unknown. Thus, this study aimed to update the information on the composition of Strophanthus seeds used for this purpose. The distribution of two main saponins and about 90 previously unreported compounds, tentatively identified as saponins in eleven Strophanthus species, was systematically evaluated by ultra-high-performance liquid chromatography mass spectrometry (UHPLC-MS) and -MS/MS. Seeds of S. gratus were selected to isolate the dominant unreported triterpenoids, bidesmosides of echinocystic and oleanolic acid. Their structures were established by HRMS, MS/MS, as well as by NMR techniques. The total saponin content, estimated by UHPLC-MS, was up to 1%. The detected saponins could influence the peroral bioavailability of hardly absorbable Strophanthus cardenolides and exhibit their own activity. This finding may be relevant when Strophanthus preparations (containing both saponins and cardiac glycosides) are used, particularly when homemade preparations are administered.

Key words

Apocynaceae - bidesmosidic triterpene saponin - cardenolides bioavailability - echinocystic acid glycoside - Strophanthus gratus - Strophanthus seeds

Publikationsverlauf

Eingereicht: 16. Februar 2021

Angenommen nach Revision: 09. August 2021

Artikel online veröffentlicht:
02. September 2021

• References

• 1 Beentje HJ. A monograph on Strophanthus DC. (Apocynaceae). Wageningen, Netherlands: H. Veenman & Zonen B. V.; 1982. Accessed August 24, 2020 at: https://edepot.wur.nl/163582
• 2 Sennblad B, Bremer B. Classification of Apocynaceae s.l. according to a new approach combining linnaean and phylogenetic taxonomy. Syst Biol 2002; 51: 389-409
• 3 Strophanthus DC. Apocynaceae. In: Quattrocchi U, ed. CRC World Dictionary of Medicinal and Poisonous Plants: Common Names, Scientific Names, Eponyms, Synonyms, and Etymology. Boca Raton, USA: CRC Press;; 2012: 3589-3595
• 4 Livingstone D, Livingstone C. Narrative of an Expedition to the Zambesi and its Tributaries, and of the Discovery of the Lakes Shirwa and Nyassa: 1858 – 1864. London, UK: John Murray; 1865
• 5 Fraenkel A, Thauer R. Strophanthin-Therapie. Berlin, Germany: Verlag von Julius Springer; 1933
• 6 Greeff K, Schadewaldt H. Introduction and remarks on the history of cardiac glycosides. In: Greeff K, ed. Cardiac Glycosides Part I: Experimental Pharmacology. Berlin-Heidelberg-New York: Springer; 1981: 1-12
• 7 Hoffmann-Bohn K, Huebl G. Strophanthus. In: Hänsel R, Keller K, Rimpler H, Schneider G, ed. Hagers Handbuch der Pharmazeutischen Praxis, Vol. 6 Berlin, Heidelberg, New York: Springer; 1994: 792-816
• 8 Catarino L, Havik PJ, Romeiras MM. Medicinal plants of Guinea-Bissau: Therapeutic applications, ethnic diversity and knowledge transfer. J Ethnopharmacol 2016; 183: 71-94
• 9 Novotna B, Polesny Z, Pinto-Basto MF, Van Damme P, Pudil P, Mazancova J, Duarte MC. Medicinal plants used by ʼroot doctorsʼ, local traditional healers in Bié province, Angola. J Ethnopharmacol 2020; 260: 112662
• 10 Nsimundele L. Répertoire des plantes médicinales des régions côtieres du Mayumbe et du Bas-Congo, 1966–1968. Notes non publiées de Léopold Nsimundele. 1968. Accessed August 24, 2020 at: http://www.ethnopharmacologia.org/prelude2020/pdf/biblio-hn-36-nsimundele.pdf
• 11 Neuwinger HD. Strophanthus. In: Neuwinger HD. ed. African Traditional Medicine. Stuttgart, Germany: Medpharm Scientific Publischers; 2000: 498-500
• 12 Wiersema JE, Léon B. Strophanthus. In: Wiersema JE, Léon B, ed. World Economic Plants: A Standard Reference. Boca Raton, USA: CRC Press; 2013: 664
• 13 Petry RJ. Die Lösung des Herzinfarkt-Problems durch g-Strophanthin. Erfahrungsheilkunde 2004; 53: 65-73
• 14 Fürstenwerth H. Ouabain – The insulin of the heart. Int J Clin Pract 2010; 64: 1591-1594
• 15 Debusmann W. Strophanthus eingetragener Verein. 2020 Accessed August 24, 2020 at: http://www.strophantus.de/
• 16 Kracke R. Zur perlingualen Strophanthintherapie. DMW – Dtsch Medizinische Wochenschrift 1954; 79: 81-83
• 17 Shah Y. Heilpflanzenporträt: Strophanthus . Z Komplementärmedizin 2011; 3: 58
• 18 [Anonymous] G-Strophanthin, Ouabain, Angina Pectoris, Strophantin-shop, Antwerpen. 2020 Accessed September 1, 2020 at: https://web.archive.org/web/20200923145927/https://www.strophantin-shop.com/
• 19 Hegnauer R. Apocynaceae. Andere isoprenoide Verbindungen. Saponine. In: Hegnauer R Chemotaxonomie der Pflanzen. III. Basel, Switzerland: Birkhäuser; 1964: 148-149
• 20 de Wildeman E. A propos de médicaments antilépreux dʼorigine végétale IV. Des Strophanthus et de leur utilisation en médecine. Mem Inst R Colon Belge Sect des Sci Nat Medicales 1946; 15: 1-70 Accessed August 24, 2020 at: https://www.kaowarsom.be/documents/MEMOIRES_VERHANDELINGEN/Sciences_naturelles_medicales/Nat.Sc.(IRCB)_T.XV,4_DE WILDEMAN, E._A propos de médicaments antilépreux d'origine végétale IV. Des Strophanthus
• 21 Barton DHR, Mohr K, Reichstein T, Schindler O. Identifizierung von Substanz Nr. 752 mit Echinocystsäure. Helv Chim Acta 1956; 39: 413-417
• 22 von Euw J, Mohr K, Schindler O, Reichstein T. Die Glykoside der Samen von Strophanthus sarmentosus var. major Dewèvre. Die Glykoside der Samen von Strophanthus sarmentosus A. P. DC., 7. Mitteilung. Glykoside und Aglykone, 158. Mitteilung. Helv Chim Acta 1956; 39: 326-330
• 23 Trotin F, Bézanger-Beauquesne L, Pinkas M. Saponosides des Apocynacées. I – extraction des saponosides des graines de Strophanthus gratus Franchet. Plantes médicinales et phytothérapie 1977; 11: 236-240
• 24 EMA Committee on Herbal Medicinal Products (HMPC). Assessment report on on Primula veris L. and/or Primula elatior (L.) Hill, radix. 2012. Accessed August 24, 2020 at: https://www.ema.europa.eu/en/documents/herbal-report/final-assessment-report-primula-veris-l/primula-elatior-l-hill-radix_en.pdf
• 25 Mahato SB, Kundu AP. ¹³C NMR Spectra of pentacyclic triterpenoids–a compilation and some salient features. Phytochemistry 1994; 37: 1517-1575
• 26 Borel C, Gupta MP, Hostettmann K. Molluscicidal saponins from Swartzia simplex . Phytochemistry 1987; 26: 2685-2689
• 27 Sosa A, Rosquete C, Rojas L, Pouységu L, Quideau S, Paululat T, Mitaine-Offer AC, Lacaille-Dubois MA. New triterpenoid and ergostane glycosides from the leaves of Hydrocotyle umbellata L. Helv Chim Acta 2011; 94: 1850-1859
• 28 Rashmi. Rameshwar D, Nagatsu A. Three oleanolic acid glycosides from the seeds of Achyranthes aspera . Nat Prod Commun 2007; 2: 727-730
• 29 Forgacs P, Provost J. Olaxoside, a saponin from Olax andronensis, Olax glabriflora and Olax psittacorum . Phytochemistry 1981; 20: 1689-1691
• 30 Schteingart CD, Pomilio AB. Two saponins from Zexmenia buphthalmiflora . Phytochemistry 1984; 23: 2907-2910
• 31 Borel C, Hostettmann K. Molluscicidal saponins from Swartzia madagascariensis Desvaux. Helv Chim Acta 1987; 70: 570-576
• 32 Yahara S, Ding N, Nohara T. Oleanane glycosides from Eclipta alba . Chem Pharm Bull 1994; 42: 1336-1338
• 33 [Anonymous] Tinctura Strophanthi. In: Deutsches Arzneibuch. 6. Nachdruck. Berlin, Germany: VEB Volk und Gesundheit; 1959: 383-384
• 34 Melek FR, Miyase T, El-Gindi OD, Abdel-Khalika SM, Haggag MY. Saponins from Fagonia mollis . Phytochemistry 1996; 42: 1405-1407
• 35 Yuan W, Wang P, Zhang Z, Su Z, Li S. Triterpenoid saponins from Sesbania vesicaria . Phytochem Lett 2013; 6: 106-109
• 36 Holzinger F, Chenot JF. Systematic review of clinical trials assessing the effectiveness of ivy leaf (Hedera helix) for acute upper respiratory tract infections. Evidence-Based Complement Altern Med 2011; 2011: 1-9
• 37 Schreier S, Malheiros SVP, De Paula E. Surface active drugs: Self-association and interaction with membranes and surfactants. Physicochemical and biological aspects. Biochim Biophys Acta – Biomembr 2000; 1508: 210-234
• 38 Pathak K, Raghuvanshi S. Oral bioavailability: Issues and solutions via nanoformulations. Clin Pharmacokinet 2015; 54: 325-357
• 39 Chao AC, Nguyen JV, Broughall M, Recchia J, Kensil CR, Daddona PE, Fix JA. Enhancement of intestinal model compound transport by DS-1, a modified Quillaja saponin. J Pharm Sci 1998; 87: 1395-1399
• 40 Kręgiel D, Berlowska J, Witońska I, Antolak H, Proestos C, Babic M, Babic L, Zhang B. Saponin-based, biological-active surfactants from plants. In: Najjar R Application and Characterization of Surfactants. London, UK: InTech; 2017: 183-205
• 41 Oleszek W, Hamed A. Saponin-Based Surfactants. In: Kjellin M, Johansson I Surfactants from Renewable Resources. Chichester, UK: John Wiley & Sons, Ltd.; 2010: 239-249
• 42 Sadgrove NJ, Jones GL. From petri dish to patient: Bioavailability estimation and mechanism of action for antimicrobial and immunomodulatory natural products. Front Microbiol 2019; 10: 1-26
• 43 Al-Ali AAA, Steffansen B, Holm R, Nielsen CU. Nonionic surfactants increase digoxin absorption in Caco-2 and MDCKII MDR1 cells: Impact on P-glycoprotein inhibition, barrier function, and repeated cellular exposure. Int J Pharm 2018; 551: 270-280
• 44 Fürstenwerth H. Comment on: Endogenous ouabain and related genes in the translation from hypertension to renal diseases. Int J Mol Sci 2019; 20: 10-13
• 45 Fürstenwerth H. On the differences between ouabain and digitalis glycosides. Am J Ther 2014; 21: 35-42
• 46 Fürstenwerth H. Ouabain – A gift from paradise. Cardiovasc Disord Med 2018; 3: 1-2
• 47 Gleńsk M, Włodarczyk M, Bassarello C, Pizza C, Stefanowicz P, Świtalska M. A major saponin from leaves extract of Acer velutinum . Z Naturforsch Sect B – J Chem Sci 2009; 64b: 1081-1086
• 48 Włodarczyk M, Pasikowski P, Osiewała K, Frankiewicz A, Dryś A, Gleńsk M. In search of high-yielding and single-compound-yielding plants: New sources of pharmaceutically important saponins from the Primulaceae family. Biomolecules 2020; 10: 1-19
• 49 Włodarczyk M, Matysik G, Cisowski W, Gleńsk M. Rapid densitometric quantitative screening of the myricitrin content of crude methanolic extracts of leaves from a variety of Acer species. J Planar Chromatogr 2006; 19: 378-382
• 50 Włodarczyk M, Szumny A, Gleńsk M. Lanostane-type saponins from Vitaliana primuliflora . Molecules 2019; 24: 1-18
• 51 Hammer Ø, Harper DAT, Ryan PD. Past: Paleontological statistics software package for education and data analysis. Palaeontol Electron 2001; 4: art. 4, 1–9. Accessed August 24, 2020 at: http://palaeo-electronica.org/2001_1/past/issue1_01.htm