Evaluation of transdermal administration of alfa-cyperone (4,11selinadien-3-one) isolated from purple nutsedge (Cyperus rotundus) essential oils as a new drug delivery treatment method for lowering cholesterol

Abstract

The compound alfa-cyperone (4, 11-selinadien-3-one) isolated from purple nutsedge (Cyperus rotundus) essential oil was investigated for cholesterol lowering effect.  In this study, we removed the hair from the back area of the rats, this compound gave us a good result as an alternative drug for lowering serum cholesterol levels via the transdermal route of administration. This compound significantly decreased total serum cholesterol level in rats at p ≤ 0.01.

Keywords

• Transdermal administration, cholesterol-lowering drug, Cyperus rotundus, liver

Kaynakça

1. Alexander A., Dwivedi S., Ajazuddin, & Giri T. K., (2012). Saraf, S, Shailendra S, Tripathi D.K. (2012). Approaches for breaking the barriers of drug permeation through transdermal drug delivery. Journal of Controlled Release 164, 26–40.
2. American Academy of Family Physicians, 2011.
3. Aqil M., Ahad A., Sultana Y., & Ali A. (2007). Status of terpenes as skin penetration enhancers. Drug Discovery Today, 12, 1061-1067.
4. Barry B. W. (2001). Novel mechanisms and devices to enable successful transdermal drug delivery. European J of pharmaceutical science, 14, 101-114.
5. Barry W.B. (2001). Is transdermal drug delivery research still important today? Drug Discovery Today, 6(19), 967-971.
6. Barry B.W. and Williams, A. C. (1995) Permeation enhancement through skin, In: Swarbrick, J., Boylan, J.C. (Eds.), Encyclopaedia of Pharmaceutical Technology, vol. 11, Marcel Dekker, New York, pp. 449– 493.
7. Bedi, M., Niesen M., Lopez, D. (2008). Inhibition of squalene synthase upregulates PCSK9 expression in rat liver. Arch Biochem Biophys, 470(2),: 116-119.
8. Bottomley M. J., Cirillo A., Orsatti L., Ruggeri L., Fisher T.S., Santoro J. C., Cummings R. T., Cubbon R. M., Lo Surdo, P., & Calzetta, A. (2009). Structural and biochemical characterization of the wild type PCSK9-EGF (AB) complex and natural familialhypercholesterolemia mutants. J Biol Chem, 284, 1313-1323.

9. Cameron, J., Ranheim, T., Kulseth, M. A., & Leren T. P. (2008). Berge KE. Berberine decreases PCSK9 expression in HepG2 cells. Atherosclerosis J, 201(2), 266-273.
10. Chen H. C., Mendelsohn R., Rerek M.E., Moore D.J. (2000). Fourier transform infrared spectroscopy and differential scanning calorimetry studies of fatty acid homogeneous ceramide 2. Biochim Biophys Acta, 1468, 293-303.
11. Chien Y. W. (1992). Novel Drug Delivery Systems. 2nd ed. p.797. New York, NY: Marcel Dekker, Inc.
12. Cornwell P. A., & Barry B. W. (1993). The routes of penetration of ions and 5-fluorouracil across human skin and the mechanisms of action of terpene skin penetration enhancers. Int J Pharm, 94,189-194.
13. Cornwell P. A., Barry B.W., Bouwstra J.A., Gooris G.S., &. (1996). Modes of action of terpene penetration enhancers in human skin; Differential scanning calorimetry, small-angle X-ray diffraction and enhancer uptake studies. Int J Pharm, 127, 9-26.
14. Dhillon, R. S., Singh, S., Kundra, S. & Basra, A.S. (1993). Studies on the chemical composition and biological activity of essential oil from Cyperus rotundus Linn. Plant Growth Regul., 13, 89-93.
15. Durate, M. C. T., Figueira, G.M., Sartoratto, A., Rehder & V.L.G., Delarmelina, C. (2005). Anti-Candida activity of Brazilian medicinal plant. J. Ethnopharmacology, 97, 305-311.
16. El-Kattan A. F., Asbill C.S., & Michniak B.B. (2000). The effect of terpene enhancer lipophilicity on the percutaneous permeation of hydrocortisone formulated in HPMC gel systems. Int J Pharm, 198, 179-189.
17. Fan D, Yancey P. G., Qiu S., Ding L. , Weeber E.J., Linton M.F.,& Fazio S. (2008). Self-association of human PCSK9 correlates with its LDLR-degrading activity. Biochemistry, 47, 1631-1639.
18. Fang, J. Y., Leu Y. L., Hwang T.L., Chen H. C., & Hung C. F. (2003). Development of sesquiterpenes from Alpinia oxyphylla as novel skin permeation enhancers. Eur J Pharm Sci, 19, 253-262.
19. Foldvari M. (2000). Non-invasive administration of drugs through the skin: challenges in delivery system design. Pharm Sci Technol Today, , 3,417-425.
20. Gao S., & Singh J. (1998). In vitro percutaneous absorption enhancement of a lipophilic drug tamoxifen by terpenes. J Control Release, 51,193-199.
21. Goldstein J. L., & Brown M. S. (2009). The LDL receptor. Arterioscler Thromb Vasc Biol, 29, 431-438.
22. Hadgraft, J. (2004). Skin deep. Eur J Pharm Biopharm, 58, 291-299.
23. Horton J.D., Cohen J.C., & Hobbs H.H. (2009). PCSK9: a convertase that coordinates LDL catabolism. J Lipid Res, 50 Suppl: S172-S177.
24. Hsieh D. S. (1994). Understanding permeation enhancement technologies. In Hsieh, D.S. (ed) Drug Permeation Enhancement: Theory and Applications. Marcel Dekker, New York, NY, USA, pp 3-17.
25. Jain A. K., Thomas N. S., & Panchagnula R. (2002). Transdermal drug delivery of imipramine hydrochloride: Effect of terpenes. J Control Release, 79, 93-101.
26. Kilani, S., Ben Ammar, R., Bouhlel, I., Abdelwahed, A., Hayder, N., Mahmoud, A., Ghedira, K.,Chekir-Ghedira, L.(2005). Investigation of extracts from (Tunisian) Cyperus rotundus as antimutagens and radical scavengers. Environ. Toxicol. Pharmacol, 20, 478-484.
27. Kilani, S., Ben Sghaier, M., Limem, I.,Bouhlel, I., Boubaker, J., Bhouri, W., Skandrani, I., Neffatti, A., Ben Ammar, R., Dijoux-Franca, M.G., Ghedira, K.,& Chekir-Ghedira, L.(2008). In vitro evaluation of antibacterial, antioxidant, cytotoxic and apoptotic activities of the tubers infusion and extracts of Cyperus rotundus. Bioresour. Technol., 99, 9004-9008.
28. Kilani, S., Bouhlel, I., Ben Ammar, R., Ben Sghair, M., Skandrani, I., Boubaker, J., Mahmoud, A., Dijoux-Franca, M.G., Ghedira, K., Chekir-Ghedira, L.(2007). Chemical investigation of different extracts and essential oil from the tubers of (Tunisian) Cyperus rotundus. Correlation with their antiradical and antimutagenic properties. Ann. Microbiol. , 57, 657-664.
29. Kilani, S., Ledauphin, J., Bouhlel, I., Ben Sghaier, M., Boubaker, J., Skandrani, I., Mosrati, R., Ghedira, K., Barillier, D. & Chekir-Ghedira L. (2008). Comparative study of Cyperus rotundus essential oil by a modified GC/MS analysis method. Evaluation of its antioxidant, cytotoxic, and apoptotic effects. Chem. Biodivers., 5, 729-742.
30. Kumar, V.S., Niranjan S. K., Irchhaiya R., Neeraj K., & Ali A. A. (2012). Novel transdermal drug delivery system. Int Res J Pharm, 3(8), 39-44.
31. Lagace T. A., Curtis D.E., Garuti R., McNutt M. C., Park S. W., Prather H. B., Anderson N. N., Ho Y. K., Hammer R.E.,& Horton J.D. (2006). Secreted PCSK9 decreases the number of LDL receptors in hepatocytes and in livers of parabiotic mice. J Clin Invest, 116, 2995-3005.
32. Law S., Wertz P. W., Swartzendruber D. C., Squier C. A. (1995). Regional variation in content, composition and organisation of porcine epithelial barrier lipids revealed by thin-layer chromatography and transmission electron microscopy. Arch Oral Biol, 40, 1085-1091.
33. Luna, L. C. (1968). Manual of histologic staining methods of the armed forces. Institute of Pathology, 3rd ed, 9, 1-74. New York, London: McGraw-Hill Book.
34. Marsh E. W., Leopold P. L., Jones N. L., & Maxfield F. R. (1995). Oligomerized transferrin receptors are selectively retained by a luminal sorting signal in a long-lived endocytic recycling compartment. J Cell Biol, 129, 1509-1522.
35. Maxfield F. R. & van der Meer G. (2010). Cholesterol, the central lipid of mammalian cells. Curr Opin Cell Biol, 22, 422-429.
36. McDougal, J. N. & Jurgens-Whitehead J. L. (2001). Short-Term Dermal Absorption and Penetration of Chemicals from Aqueous Solutions: Theory and Experiment. J Risk Anal, 21(4), 719-726.
37. Mesher, A. L. (2010). Junqueira's Basic Histology, Twelfth Edition. The McGraw-Hill.
38. Mohammad Zafar Imam & Chandra Datta Sumi. (2014).Evaluation of antinociceptive activity of hydromethanol extract of Cyperus rotundus in mice.BMC Complement Altern Med, 5.DOI: 10.1186/1472- 6882-14-83
39. Monti D., Chetoni P., Burgalassi S., Najarro M., Saettone M.F., & Boldrini E. (2002). Effect of different terpene- containing essential oils on permeation of estradiol through hairless mouse skin. Int J Pharm, 237,209-214.
40. Morimoto Y., Wada Y., Seki T., & Sugibayashi K. (2002). In vitro skin permeation of morphine hydrochloride during the finite application of penetration-enhancing system containing water, ethanol and L-menthol. Biol Pharm Bull, 25,134-136.
41. Mousavi S. A., Berge K. E., & Leren T. P. (2009). The unique role of proprotein convertase subtilisin/kexin 9 in cholesterol homeostasis. J Intern Med, 266, 507-519.
42. Nagulendran KR., Velavan S., Mahesh R., & Hazeena Begum V.(2007). In Vitro Antioxidant Activity and Total Polyphenolic Content of Cyperus rotundus Rhizomes. E-Journal of Chemistry, 4, 440-449.
43. National Research Council. (2002). Ethical Guide for the Care and Use of Laboratory Animals. National Academy Press, 6th ed. Washington D.C.
44. Pal, D.K. & Dutta, S. (2006). Evaluation of the Antioxidant activity of the roots and Rhizomes of Cyperus rotundus L. Indian J. Pharm. Sci., 68,: 256-258.
45. Park D., Park H., Seo J., &Lee S. (2014). Sonophoresis in transdermal drug deliverys. Ultrasonics. 54(1), 56- 65.
46. Poonam G. D, S. Brijesh, Pundarikakshudu T., & Tannaz J. B. (2011). Studies on the activity of Cyperus rotundus Linn. tubers against infectious diarrhea. Indian J Pharmacol. , 43(3), 340–344.
47. Raut, N.A.& Gaikwad, N.J. (2006) Antidiabetic activity of hydro-ethanolic extract of Cyperus rotundus in alloxan induced diabetes in rats. Fitoterapia, 77, 585–588.
48. Sandeep, B, Kangralkar, V.A., Mandavkar Y., Thakur M., & Chougulen, N. (2010). Antinflammatory, Antiarthritic , Analgesic and Anticonvulsant activity of Cyperus essential oils. International Journal of Pharmacy and Pharmaceutical Sciences, 2, 112-115.
49. Sawanee K., Kwunchit O., & Supinya T. (2008). Anti-allergic activity of Thai medicinal plants used in longevity formulation. Songklanakarin J. Sci. Technol., 30, 621-625.
50. Seidah, N.G., Benjannet S., Wickham L., Marcinkiewicz J., Jasmin, S.B., Stifani S., Basak A., Prat, A., & Chretien M. (2003).The secretory proprotein convertase neural apoptosis-regulated convertase 1 (NARC-1): liver regeneration
51. 1073/pnas.0335507100
52. neuronal differentiation. Proc .Natl.
53. Acad. Sci. USA. 928–933,
54. doi: Shah, V.P. (1994). Skin penetration enhancers: Scientific perspectives. In Hsieh, D.S. (ed) Drug Permeation Enhancement: Theory and Applications. Marcel Dekker, New York, NY, USA, pp 19-23.
55. Singh I., & Morris A.P.(2011). Performance of transdermal therapeutic systems: Effects of biological factors. Int J Pharm Investig, 1(1),: 4-9.
56. Singh S. P., Raghavendra K., & Dash, A. P. (2009). Evaluation of Hexane Extract of Tuber of Root of Cyperus rotundus Linn (Cyperaceae) for Repellency against Mosquito Vectors. Journal of Parasitology Research, 5. http://dx.doi.org/10.1155/2009/908085.
57. Sundaram, M. S., Sivakumar, T. B & Balamurugan, G. (2008). Anti-inflammatory effect of Cyperus rotundus Linn. Leaves on acute and subacute inflammation in experimental rat models. Biomedicine, 28, 302-304.
58. Tavori H., Fan D., Blakemore J.L., Yancey P.G., Ding L., Linton M.F., & Fazio S.(2013). Serum proprotein convertase subtilisin/kexin type 9 and cell surface low-density lipoprotein receptor: evidence for a reciprocal regulation. Circulation, 18,127(24), 2403-13.
59. Thomas B. J., & Finnin B.C. (2004).The transdermal revolution. Drug Discov Today, 9, :697-703.
60. Uddin, S.J., Mondal, K., Shilpi, J.A.&Rahman, M.T. (2006). Antidiarrhoeal activity of Cyperus rotundus. Fitoterapia, 77, 134–136.
61. Walker R. B., & Smith E.W. (1996). The role of percutaneous penetration enhancers. Adv Drug Deliver Rev, 18, 295-301.
62. Williams A. C. & Barry B. W. (1989). Essential oils as novel human skin penetration enhancers. Int J Pharm, 57 (2), R7–R9.
63. Williams A. C., & Barry B. W. (2012).Penetration enhancers. Adv Drug Deliver Rev, 64,128-137.
64. Yokoi K., Kawaaib T., Konomi A., & Uchida Y. (2008). Dermal absorption of inorganic germanium in rats. Reg Tox Pharm, 52(2), 169-173.
65. Yourick, J. J. , & Bronaugh R. L. (1997).Percutaneous Absorption and Metabolism of Coumarin in Human and Rat Skin. J Appl Tox, 17(3), 153-158.
66. Zhang D. W., Garuti R., Tang W. J., Cohen J. C., & Hobbs H. H. (2008). Structural requirements for PCSK9- mediated degradation of the lowdensity lipoprotein receptor. Proc.Natl.Acad.Sci USA 105, 13045-13050.
67. Zhang D. W., Lagace T. A., Garuti R., Zhao Z., McDonald M., Horton J. D., Cohen J. C., & Hobbs H. H. (2007). Binding of proprotein convertase subtilisin/kexin type 9 to epidermal growth factor-like repeat A of low density lipoprotein receptor decreases receptor recycling and increases degradation. J Biol Chem, 282, 18602-18612.
68. Zhu, M., Luk, H. H., Fung, H.S. & Luk, C.T. (1997). Cytoprotective effects of Cyperus rotundus against ethanol induced gastric ulceration in rats. Phytother. Res., 1997, 11, 392 -394.