Journal of Natural Medicines

, Volume 71, Issue 1, pp 272–280 | Cite as

Securigenin glycosides as hypoglycemic principles of Securigera securidaca seeds

  • Zahra Tofighi
  • Fahimeh Moradi-Afrapoli
  • Samad Nejad Ebrahimi
  • Saied Goodarzi
  • Abbas Hadjiakhoondi
  • Markus Neuburger
  • Matthias Hamburger
  • Mohammad Abdollahi
  • Narguess Yassa
Original Paper
  • 205 Downloads

Abstract

Seeds of Securigera securidaca (Fabaceae) are used in Iranian folk medicine as an antidiabetic treatment. In this study, the antihyperglycemic activity of chloroform and methanol fractions (CF and MF) from S. securidaca seed extract was investigated and their bioactive constituents were identified. The antidiabetic effects of fractions were assessed by streptozocin-induced diabetic Naval Medical Research Institute mice. The hypoglycemic activity of MF at 100 mg/kg and CF at 400 mg/kg was comparable with glibenclamide (3 mg/kg). MF at 400 mg/kg and CF at 600 mg/kg showed equal hypoglycemic responses to 12.5 IU/kg insulin (P > 0.05). Three cardiac glycosides were isolated as active constituents responsible for the hypoglycemic activity. Securigenin-3- O -β-glucopyranosyl-(1 → 4)-β-xylopyranoside (1) was a major compound in seeds. Securigenin-3- O -inositol-(1 → 3)-β-glucopyranosyl-(1 → 4)-β-xylopyranoside (2) and securigenin-3- O -α-rhamnopyranosyl-(1 → 4)-α-glucopyranoside (3) were found as new natural products. When 1–3 were tested at 10 mg/kg there was a significant reduction of blood glucose levels in diabetic mice, comparable to that of 3 mg/kg glibenclamide (P > 0.05). The hypoglycemic effect was due to an increase in insulin secretion; the insulin levels in the diabetic mice significantly improved and were comparable with those in healthy animals (P > 0.05). Compounds responsible for the hypoglycemic properties of S. securidaca seeds were identified as cardiac glycosides and were found to act via an increase of insulin levels in a diabetic mouse model.

Keywords

Securigera securidaca Antidiabetic activity Cardenolides Securigenin glycosides Insulin secretion 

Notes

Acknowledgements

This research was a part of PhD thesis and it was supported by Tehran University of Medical Sciences and Health Services Grants (Nos. 11981 and 13726).

Supplementary material

11418_2016_1060_MOESM1_ESM.docx (17 mb)
Supplementary material 1 (DOCX 17430 kb)
11418_2016_1060_MOESM2_ESM.docx (440 kb)
Supplementary material 2 (DOCX 440 kb)

References

  1. 1.
    Rechinger KH (1984) Papilionaceae II. In: Rechinger KH (ed) Flora Iranica 157. Akademische Druck und Verlagsanstalt, AustriaGoogle Scholar
  2. 2.
    Ali AA, Mohamed MH, Kamel MS, Fouad MA, Spring O (1998) Studies on Securigera securidaca (L.) Deg. Et Dorfl. (Fabaceae) seeds, an antidiabetic Egyptian folk medicine. Pharmazie 53:710–715PubMedGoogle Scholar
  3. 3.
    Porchezhian E, Ansari SH (2001) Effect of Securigera securidaca on blood glucose levels of normal and alloxan-induced diabetic rats. Pharm Biol 39:62–64CrossRefGoogle Scholar
  4. 4.
    Nagarajan S, Jain HC, Aulakh GS (1982) Indigenous plants used in the control of diabetes. In: Atal C, Kapur B (eds) Cultivation and utilization of medicinal plants. Regional Research Laboratory, India, pp 584–604Google Scholar
  5. 5.
    Hosseinzadeh H, Ramezani M, Danaei AR (2002) Antihyperglycaemic effect and acute toxicity of Securigera securidaca L. seed extracts in mice. Phytother Res 16:745–747CrossRefPubMedGoogle Scholar
  6. 6.
    Zahedi Asl S, Marahel H, Zare B (2005) Study on the effects of chloroformic extract of Securigera securidaca on serum glucose level and liver glycogen content of mice. J Kerman Univ Med Sci 12:32–38Google Scholar
  7. 7.
    Ghitasi I, Nikbakht MR, Sadeghi H, Sabzali V, Sabzali S, Shahrani M (2007) The hypoglycemic effects of a hydro-alcoholic extract from Securigera securidaca seeds on induced diabetic in male rats. J Shahrekord Univ Med Sci 8:68–73Google Scholar
  8. 8.
    Pouramir M, Shahaboddin ME, Moghadamnia AA, Parastouei K (2011) To study the effects of Securigera securidaca (L.) seed against alloxan-induced hyperglycemia. J Med Plants Res 5:3188–3191Google Scholar
  9. 9.
    Roostazadeh A, Firoozrai M, Shabani M (2008) Effect of aqueous seed extract of Securigera securidaca on erythrocytes catalase activity in type 1 diabetic rats. Qom Univ Med Sci J 1:9–14Google Scholar
  10. 10.
    Al-Hachhim G, Maki B (1969) Effect of Securigera securidaca on electroshock seizure threshold in mice. Psychol Rep 24:551–553CrossRefGoogle Scholar
  11. 11.
    Mard SA, Bahari Z, Eshaghi N, Farbood Y (2008) Antiulcerogenic effect of Securigera securidaca L. seed extract on various experimental gastric ulcer models in rats. Pak J Biol Sci 11:2619–2623CrossRefPubMedGoogle Scholar
  12. 12.
    Azarmiy Y, Zakheri A, Allaf Akbari N, Fathi Azad F, Fakhrjo A, Andalib S, Maleki Dizaji N, Babaei H, Garjani A (2009) The effect of total extract of Securigera securidaca L. seed on thoracic aorta function in nigh-fat fed rats. Pharm Sci 15:83–92Google Scholar
  13. 13.
    Garjani A, Fathiazad F, Zakheri A, Akbari NA, Azarmie Y, Fakhrjoo A, Andalib S, Maleki Dizaji N (2009) The effect of total extract of Securigera securidaca L. seeds on serum lipid profiles, antioxidant status, and vascular function in hypercholesterolemic rats. J Ethnopharmacol 126:525–532CrossRefPubMedGoogle Scholar
  14. 14.
    Shahidi S, Pahlevani P (2013) Antinociceptive effects of an extract of Securigera securidaca and their mechanisms in mice. Neurophysiology 45:34–38CrossRefGoogle Scholar
  15. 15.
    Tofighi Z, Asgharian P, Goodarzi S, Hadjiakhoondi A, Ostad SN, Yassa N (2014) Potent cytotoxic flavonoids from Iranian Securigera securidaca. Med Chem Res 23:1718–1724CrossRefGoogle Scholar
  16. 16.
    Zamula VV, Maksyutina NP, Kolesnikov DG (1965) Cardenolides of Securigera securidaca II. Chem Nat Compd 1:117–119CrossRefGoogle Scholar
  17. 17.
    Zatula VV, Chernobrovaya NV, Kolesnikov DG (1966) The structure of securigenin and its biosidesecuridaside. Khim Prir Soedin 2:438–439Google Scholar
  18. 18.
    Komissarenko AN, Kovalev VN (1987) Hydroxycoumarins and flavones of Securigera securidaca. Khim Prir Soedin 2:298–299Google Scholar
  19. 19.
    Tofighi Z, Alipour F, Hadavinia H, Abdollahi M, Hadjiakhoondi A, Yassa N (2014) Effective antidiabetic and antioxidant fractions of Otostegia persica extract and their constituents. Pharma Biol 52:961–966CrossRefGoogle Scholar
  20. 20.
    Yassa N, Saeidnia S, Pirouzi R, Akbaripour M, Shafiee A (2007) Three phenolic glycosides and immunological properties of Achillea millefolium from Iran, population Golestan. Daru 15:49–52Google Scholar
  21. 21.
    Bruker (2006) Bruker Analytical X-Ray Systems, Inc. apex 2, version 2 ed. Madison, M86-E01078Google Scholar
  22. 22.
    Altomare A, Cascarano G, Giacovazzo C, Guagliardi A, Burla MC, Polidori G, Camalli M (1994) A program for automatic solution of crystal structures by direct methods optimized for powder data. J Appl Crystallogr 27:435–436Google Scholar
  23. 23.
    Betteridge PW, Carruthers JR, Cooper RI, Prout K, Watkin DJ (2003) CRYSTALS version 12: software for guided crystal structure analysis. J Appl Crystallogr 36:1487CrossRefGoogle Scholar
  24. 24.
    Prince E (1982) Mathematical techniques in crystallography and materials science. Springer, New York, pp 12–13 (Duoc Hoc 6) CrossRefGoogle Scholar
  25. 25.
    Watkin DJ (1994) The control of difficult refinements. Acta Crystallogr A 50:411–437CrossRefGoogle Scholar
  26. 26.
    Macrae CF, Bruno IJ, Chisholm JA, Edgington PR, McCabe P, Pidcock E, Rodriguez-Monge L, Taylor R, Streek JV, Wood PA (2008) Mercury CSD 2.0—new features for the visualization and investigation of crystal structures. J Appl Crystallogr 41:466–470CrossRefGoogle Scholar
  27. 27.
    Ripperger HH, Lindig C, Snatzke G (1998) Circular dichroism of cardenolides. J Prak Chem-Chem ZTG 340:476–478CrossRefGoogle Scholar
  28. 28.
    Bagirov RB, Komissarenko NF (1966) New cardenolides from the seeds of Coronilla hyrcana. Khim Prir Soedin 2:251–257Google Scholar
  29. 29.
    Hembree JA, Chang CJ, McLaughlin JL, Peck G, Cassady JM (1979) Potential antitumor agents: a cytotoxic cardenolide from Corronilla varia. J Nat Prod 42:293–298CrossRefGoogle Scholar
  30. 30.
    Ankli A, Heilmann J, Heinrich M, Sticher O (2000) Cytotoxic cardenolides and antibacterial terpenoids from Crossopetalum gaumeri. Phytochemistry 54:531–537CrossRefPubMedGoogle Scholar
  31. 31.
    Kasai R, Okihara M, Asakawa J, Mizutani K, Tanaka O (1979) 13C NMR study of a- and b-anomeric pairs of d-mannopyranosides and l-rhamnopyranosides. Tetrahedron 35:1427–1432CrossRefGoogle Scholar
  32. 32.
    Marles RJ, Farnsworth NR (1995) Antidiabetic plants and their active constituents. Phytomedicine 2:137–189CrossRefPubMedGoogle Scholar
  33. 33.
    Ross IA (2001) Medicinal plants of the world-chemical constituents. In: Traditional and modern uses. Human Press Inc, TotowaGoogle Scholar
  34. 34.
    Mraz M, Opletal L, Sovova M, Drasar P, Havel M (1992) Inhibition of Na+–K+ATPase by the glycosides from Coronilla varia. Planta Med 58:467–468CrossRefPubMedGoogle Scholar
  35. 35.
    Ahmad VU, Basha A (2006) Cardenolides and pregnanes. In: Ahamad VU, Basha A (ed) Spectroscopic data of steroid glycosides. Springer, New York, p 2335 Google Scholar
  36. 36.
    Triner L, Killian P, Nahas GG (1968) Ouabain hypoglycemia: insulin mediation. Science 162:560–561CrossRefPubMedGoogle Scholar
  37. 37.
    Triner L, Papayoanou J, Killian P, Vulliemoz Y, Castany R, Nahas GG (1969) Effects of ouabain on insulin secretion in the dog. Circ Res 25:119–129CrossRefPubMedGoogle Scholar
  38. 38.
    Oubaassinea R, Weckering M, Kessler L, Breidert M, Roegel JC, Eftekhari P (2012) Insulin interacts directly with Na+/K+ATPase and protects from digoxin toxicity. Toxicology 299:1–9CrossRefGoogle Scholar
  39. 39.
    Aubie A, Naranjan D, Grant P, Pawan S (2001) Diabetes and cardiovascular disease etiology, treatment and outcomes. Springer, NewYorkGoogle Scholar

Copyright information

© The Japanese Society of Pharmacognosy and Springer Japan 2016

Authors and Affiliations

  • Zahra Tofighi
    • 1
  • Fahimeh Moradi-Afrapoli
    • 2
    • 3
  • Samad Nejad Ebrahimi
    • 3
    • 4
  • Saied Goodarzi
    • 1
  • Abbas Hadjiakhoondi
    • 1
  • Markus Neuburger
    • 5
  • Matthias Hamburger
    • 3
  • Mohammad Abdollahi
    • 6
  • Narguess Yassa
    • 1
  1. 1.Department of Pharmacognosy, Faculty of Pharmacy and Medicinal Plant Research CenterTehran University of Medical SciencesTehranIran
  2. 2.Department of Pharmacognosy, Faculty of PharmacyMazandaran University of Medical SciencesSariIran
  3. 3.Department of Pharmaceutical SciencesUniversity of BaselBaselSwitzerland
  4. 4.Department of Phytochemistry, Medicinal Plants and Drugs Research InstituteShahid Beheshti UniversityTehranIran
  5. 5.Inorganic Chemistry, Department of ChemistryUniversity of BaselBaselSwitzerland
  6. 6.Department of Toxicology and Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences Research CenterTehran University of Medical SciencesTehranIran

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