Natural compounds with important medical potential found in Helleborus sp.

[1] Toma C., Rugină R., Medicinal plant’s anatomy. Atlas, [Anatomia plantelor medicinale. Atlas], Romanian Academy Ed., Bucharest, 1998 (in Romanian) Search in Google Scholar

[2] Kemertelidze E.P., Biologically active compounds and original remedies from plants growing in Georgia, Bull. Georgian Natl. Acad. Sci., 2007, 175, 91–96 Search in Google Scholar

[3] van Tellingen C., Pliny’s pharmacopoeia or the Roman treatment, Neth. Heart J., 2007, 15, 118–120 http://dx.doi.org/10.1007/BF0308596610.1007/BF03085966Search in Google Scholar

[4] Brussel D.E., Medicinal plants of Mt. Pelion, Greece, Econ. Bot., 2004, 58, S174–S202 10.1663/0013-0001(2004)58[S174:MPOMPG]2.0.CO;2Search in Google Scholar

[5] Ramoutsaki I.A., Askitopoulou H., Konsolaki E., Pain relief and sedation in Roman Byzantine texts: Mandragoras officinarum, Hyoscyamos niger and Atropa belladonna, International Congress Series, 2002, 1242, 43–50 http://dx.doi.org/10.1016/S0531-5131(02)00699-410.1016/S0531-5131(02)00699-4Search in Google Scholar

[6] Ciulei I., Grigorescu E., Stănescu U., Medicinal plants, phytochemistry and phytotherapy [Plante medicinale, fitochimie si fitoterapie, Vol. 1], Medical Ed., Bucharest, 1993 (in Romanian) Search in Google Scholar

[7] Adams M., Althera W., Kessler M., Kluge M., Hamburger M., Malaria in the renaissance: Remedies from European herbals from the 16th and 17th century, J. Ethnopharmacol., 2011, 133, 278–288 http://dx.doi.org/10.1016/j.jep.2010.10.06010.1016/j.jep.2010.10.060Search in Google Scholar

[8] Scherrer A.M., Motti R., Weckerle C.S., Traditional plant use in the areas of Monte Vesole and Ascea, Cilento National Park (Campania, Southern Italy), J. Ethnopharmacol., 2005, 97, 129–143 http://dx.doi.org/10.1016/j.jep.2004.11.00210.1016/j.jep.2004.11.002Search in Google Scholar

[9] Fujita T., Sezik E., Tabata M., Yeşilada E., Honda G., Takeda Y., et al., Traditional medicine in Turkey VII. Folk medicine in Middle and West Black Sea regions, Econ. Bot., 1995, 49, 406–422 http://dx.doi.org/10.1007/BF0286309210.1007/BF02863092Search in Google Scholar

[10] Menković N., Šavikin K., Tasić S., Zdunić G., Stešević D., Milosavljević S., et al., Ethnobotanical study on traditional uses of wild medicinal plants in Prokletije Mountains (Montenegro), J. Ethnopharmacol., 2011, 133, 97–107 http://dx.doi.org/10.1016/j.jep.2010.09.00810.1016/j.jep.2010.09.008Search in Google Scholar

[11] Idolo M., Motti R., Mazzoleni S., Ethnobotanical and phytomedicinal knowledge in a longhistory protected area, the Abruzzo, Lazio and Molise National Park (Italian Apennines), J. Ethnopharmacol., 2010, 127, 379–395 http://dx.doi.org/10.1016/j.jep.2009.10.02710.1016/j.jep.2009.10.027Search in Google Scholar

[12] Duke J.A., Bogenschutz-Godwin M.J., duCellier J., Duke P.-A.K., Handbook of Medicinal Herbs, 2nd ed., CRC Press LLC, Boca Raton, Florida, 2002 http://dx.doi.org/10.1201/978142004046310.1201/9781420040463Search in Google Scholar

[13] Adams M., Berset C., Kessler M., Hamburger M., Medicinal herbs for the treatment of rheumatic disorders—A survey of European herbals from the 16th and 17th century, J. Ethnopharmacol., 2009, 121, 343–359 http://dx.doi.org/10.1016/j.jep.2008.11.01010.1016/j.jep.2008.11.010Search in Google Scholar

[14] Gomes N.G.M., Campos M.G., Órfão J.M.C., Ribeiro C.A.F., Plants with neurobiological activity as potential targets for drug discovery, Prog. Neuro-Psychopharmacol Biol Psychiatry, 2009, 33, 1372–1389 http://dx.doi.org/10.1016/j.pnpbp.2009.07.03310.1016/j.pnpbp.2009.07.033Search in Google Scholar

[15] Jäger A.K., Gauguin B., Adsersen A., Gudiksen L., Screening of plants used in Danish folk medicine to treat epilepsy and convulsions, J. Ethnopharmacol., 2006, 105, 294–300 http://dx.doi.org/10.1016/j.jep.2005.10.01510.1016/j.jep.2005.10.015Search in Google Scholar

[16] Cornara L., La Rocca A., Marsili S., Mariotti M.G., Traditional uses of plants in the Eastern Riviera (Liguria, Italy), J. Ethnopharmacol., 2009, 125, 16–30 http://dx.doi.org/10.1016/j.jep.2009.06.02110.1016/j.jep.2009.06.021Search in Google Scholar

[17] Passalacqua N.G., De Fine G., Guarrera P.M., Contribution to the knowledge of the veterinary science and of the ethnobotany in Calabria region (Southern Italy), J. Ethnobiol. Ethnomed., 2006, 2, 52 http://dx.doi.org/10.1186/1746-4269-2-5210.1186/1746-4269-2-52Search in Google Scholar

[18] Pieroni A., Nebel S., Quave C., Münz H., Heinrich M., Ethnopharmacy of the ethnic Albanians (Arbëreshë) of northern Basilicata, Italy. Fitoterapia, 2002, 73, 217–241 http://dx.doi.org/10.1016/S0367-326X(02)00063-110.1016/S0367-326X(02)00063-1Search in Google Scholar

[19] Jarić S., Popović Z., Mačukanović-Jocić M., Djurdjević L., Mijatović M., Karadžić B., et al., An ethnobotanical study on the usage of wild medicinal herbs from Kopaonik Mountain (Central Serbia), J. Ethnopharmacol., 2007, 111, 160–175 http://dx.doi.org/10.1016/j.jep.2006.11.00710.1016/j.jep.2006.11.007Search in Google Scholar

[20] Bogdan I., Nechifor A., Basea I., Hruban E., From Romanian folk medicine: nonspecific stimulus therapy using transcutaneous implantation of hellebore (Helleborus purpurascens, Fam. Ranunculaceae) in agriculturally useful animals, Dtsch. Tieraerztl. Wochenschr., 1997, 97, 525–529 Search in Google Scholar

[21] Pârvu C., Plant’s Universe. Small encyclopaedia [Universul plantelor. Mica enciclopedie], 3rd ed., Encyclopaedia Ed., Bucharest, 2000 (in Romanian) Search in Google Scholar

[22] Hussain A., Khan M.N., Iqbal Z., Sajid M.S., An account of the botanical anthelmintics used in traditional veterinary practices in Sahiwal district of Punjab, Pakistan, J. Ethnopharmacol., 2008, 119, 185–190 http://dx.doi.org/10.1016/j.jep.2008.06.03410.1016/j.jep.2008.06.034Search in Google Scholar

[23] Pascual-Villalobos M.J., Robledo A., Screening for antiinsect activity in Mediterranean plants, Indust. Crops Prod., 1998, 8, 183–194 http://dx.doi.org/10.1016/S0926-6690(98)00002-810.1016/S0926-6690(98)00002-8Search in Google Scholar

[24] Prieto J.M., Schaffner U., Barker A., Braca A., Siciliano T., Boevé J.-L., Sequestration of furostanol saponins by Monophadnus sawfly larvae, J. Chem. Ecol., 2007, 33, 513–524 http://dx.doi.org/10.1007/s10886-006-9232-710.1007/s10886-006-9232-7Search in Google Scholar PubMed

[25] Flomenbaum N.E., Goldfrank L.R., Hoffman R.S., Howland M.A, Lewin N.A., Nelson L.S., Goldfrank’s Toxicologic Emergencies, 8th ed., McGraw Hill Companies Inc., 2006 Search in Google Scholar

[26] Bruneton J., Pharmacognosy, Phytochemistry, Medicinal plants [Pharmacognosie, Phytochimie, Plantes medicinales], 4th ed., Tec & Doc Ed., Éditions médicales internationals, Paris, France, 2009 (in French) Search in Google Scholar

[27] True B.L., Dreisbach R.H., Dreisbach’s Handbook of Poisoning: Prevention, Diagnosis & Treatment, 13th ed., The Parthenon Publishing Group, London, UK, 2002 10.1201/b14640Search in Google Scholar

[28] Cooper, M.R., Johnson A.W., Poisonous Plants & Fungi: An Illustrated Guide Stationery Office Books, Norwich, 1988 Search in Google Scholar

[29] Fuller T.C., McClintock E.M., Poisonous Plants of California, University of California Press, Berkeley, California, 1986 Search in Google Scholar

[30] Karaca S., Kulac M., Kucuker H., Phytodermatitis caused by Ceratocephalus falcatus (Ranunculaceae), Eur. J. Dermatol., 2005, 15, 404–405 Search in Google Scholar

[31] Frohne, D., Pfander, H.J., Poisonous Plants: a handbook for doctors, pharmacists toxicologists, biologists and veterinarians, 2nd ed. Manson Publishing Inc., London, 2005 Search in Google Scholar

[32] Karrer W., About hellebrin, a crystallized glycosid from Helleborus nigri roots [Über Hellebrin, ein kristalisiertes Glycosid aus Radix Hellebori nigri], Helv. Chim. Acta, 1943, 26, 1353 (in German) http://dx.doi.org/10.1002/hlca.1943026050910.1002/hlca.19430260509Search in Google Scholar

[33] Wissner W., Kating H., Botanical and phytochemical investigations of species of the genus Helleborus growing in Europe and Asian Minor. II. Comparative phytochemical investigations of the cardio active glycosides and saponins, Planta Med., 1974, 26, 228–249 http://dx.doi.org/10.1055/s-0028-109938210.1055/s-0028-1099382Search in Google Scholar

[34] Wissner W., Kating H., Botanical and phytochemical investigations of species of the genus Helleborus growing in Europe and Asian Minor — III. The quantitative contents of hellebrin in plants of the natural biotops and in culture, Planta Med., 1974, 26, 364–374 http://dx.doi.org/10.1055/s-0028-109940110.1055/s-0028-1099401Search in Google Scholar

[35] Dewick P.M., Medicinal Natural Products: A Biosynthetic Approach, 2nd ed., John Wiley & Sons Inc., New York, USA, 2002 Search in Google Scholar

[36] Gao H., Popescu R., Kopp B., Wang Z., Bufadienolides and their antitumor activity, Nat. Prod. Rep., 2011, 28, 953–969 http://dx.doi.org/10.1039/c0np00032a10.1039/c0np00032aSearch in Google Scholar

[37] Cioca C., Cucu V., Quantitative determination of hellebrin in the rhizomes and roots of Helleborus purpurascens W. et K., Planta Med., 1974, 26, 250–253 http://dx.doi.org/10.1055/s-0028-109938310.1055/s-0028-1099383Search in Google Scholar

[38] Muhr P., Kerek F., Dreveny D., Likussar W., Schubert-Zsilavecz M., The structure of hellebrin, Liebigs Ann., 1995, 2, 443–444 http://dx.doi.org/10.1002/jlac.19951995025710.1002/jlac.199519950257Search in Google Scholar

[39] Challinor V.L., Piacente S., De Voss J.J., NMR assignment of the absolute configuration of C-25 in furostanol steroidal saponins, Steroids, 2012, 77, 504–511 http://dx.doi.org/10.1016/j.steroids.2012.01.00910.1016/j.steroids.2012.01.009Search in Google Scholar

[40] Lacaille-Dubois M.A., Wagner H., A review of the biological and pharmacological activities of saponins, Phytomedicine, 1996, 2, 363–386 http://dx.doi.org/10.1016/S0944-7113(96)80081-X10.1016/S0944-7113(96)80081-XSearch in Google Scholar

[41] Lacaille-Dubois M.A., Wagner H., Bioactive saponins from plants: An update, In: Atta-ur-Rahman (Ed.), Studies in Natural Products Chemistry, Vol. 21, Elsevier, 2000 10.1016/S1572-5995(00)80015-0Search in Google Scholar

[42] Lacaille-Dubois M.A., Bioactive saponins with cancer related and immunomodulatory activity: Recent developments, In: Atta-ur-Rahman (Ed.), Studies in Natural Products Chemistry, Vol. 32, Elsevier, 2005 10.1016/S1572-5995(05)80057-2Search in Google Scholar

[43] Dinan L., Phytoecdysteroids: biological aspects, Phytochemistry, 2001, 57, 325–339 http://dx.doi.org/10.1016/S0031-9422(01)00078-410.1016/S0031-9422(01)00078-4Search in Google Scholar

[44] Walters D., Plant Defense: Warding off attack by pathogens, herbivores and parasitic plants, 1st ed., Blackwell Publishing Ltd., 2011 10.1002/9781444328547Search in Google Scholar

[45] Klein R., Phytoecdysteroids, Journal of American Herbalists Guild, 2004, 18–28 Search in Google Scholar

[46] Mares D., Antimicrobial activity of protoanemonin, a lactone from ranunculaceous plant. Mycopathologia, 1987, 98, 133–140 http://dx.doi.org/10.1007/BF0043764810.1007/BF00437648Search in Google Scholar

[47] Tocan V., Baron O., Antibiotic effect of protoanemonine isolated from Ranunculus oxyspermus M.B., Boll. Chim. Farm., 1969, 108, 789–791 Search in Google Scholar

[48] Misra S., Dixit S., Antifungal principle of Ranunculus sceleratus, Econ. Bot. 1980, 34, 362–367 http://dx.doi.org/10.1007/BF0285831210.1007/BF02858312Search in Google Scholar

[49] Minakata H., Komura H., Nakanishi K., Kada T., Protoanemonin, an antimutagen isolated from plants, Mutation Research/Genetic Toxicology, 1983, 116, 317–322 http://dx.doi.org/10.1016/0165-1218(83)90069-110.1016/0165-1218(83)90069-1Search in Google Scholar

[50] Martin M.L., San Roman L., Dominguez A., In vitro activity of protoanemonin, an antifungal agent, Planta Med., 1990, 56, 66–69 http://dx.doi.org/10.1055/s-2006-96088610.1055/s-2006-960886Search in Google Scholar

[51] Dickens F., Jones H.E.H., Carcinogenic activity of a series of reactive lactones and related substances, Br. J. Cancer, 1961, 15, 85–100 http://dx.doi.org/10.1038/bjc.1961.1010.1038/bjc.1961.10Search in Google Scholar

[52] Habermehl G.G., Ziemer P., Mitteleuropäische Giftpflanzen und ihre Wirkstoffe [Central European poisonous plants and their active ingredients] Springer, Berlin, 1999 (in German) 10.1007/978-3-642-59961-3Search in Google Scholar

[53] Martin, M.L., Ortiz de Urbina A.V., Montero M.J., Carron R., San Roman L., Pharmacologic effects of lactones isolated from Pulsatilla alpina subsp. Aphfolia, J. Ethnopharmacol., 1988, 24, 185–191 http://dx.doi.org/10.1016/0378-8741(88)90150-X10.1016/0378-8741(88)90150-XSearch in Google Scholar

[54] Roth L., Daunderer M., Kormann K., Giftpflanzen-Pflanzengifte [Poisonous plants-phytotoxins] Nikol Verlag, Hamburg, 2006 (in German) Search in Google Scholar

[55] Huang, Y.-H., Lee T.-H., Chan K.-J., Hsu F.-L., Wu Y.-C., Lee M.-H., Anemonin is a natural bioactive compound that can regulate tyrosinase-related proteins and mRNA in human melanocytes, J. Dermatol. Sci., 2008, 49, 115–123 http://dx.doi.org/10.1016/j.jdermsci.2007.07.00810.1016/j.jdermsci.2007.07.008Search in Google Scholar PubMed

[56] Hu Y., Chen X., Duan H., Hu, Y.L., Mu X., Pulsatilla decoction and its active ingredients inhibit secretion of NO, ET-1, TNF-alpha, and IL-1 alpha in LPSinduced rat intestinal microvascular endothelial cells, Cell Biochem. Funct., 2009, 27, 284–288 http://dx.doi.org/10.1002/cbf.157010.1002/cbf.1570Search in Google Scholar

[57] Duan H., Zhang Y., Xu J., Qiao J., Suo Z., Hu G., Mu X., Effect of anemonin on NO, ET-1 and ICAM-1 production in rat intestinal microvascular endothelial cells, J. Ethnopharmacol., 2006, 104, 362–366 http://dx.doi.org/10.1016/j.jep.2005.09.03410.1016/j.jep.2005.09.034Search in Google Scholar

[58] Lee T.H., Huang N.K., Lai T.C., Yang A.T.Y., Wang G.J., Anemonin, from Clematis crassifolia, potent and selective inducible nitric oxide synthase inhibitor, J. Ethnopharmacol., 2008, 116, 518–527 http://dx.doi.org/10.1016/j.jep.2007.12.01910.1016/j.jep.2007.12.019Search in Google Scholar

[59] Colombo M.L., Tome’ F., Servettaz O., Bugatti C., Phytochemical evaluation of Helleborus species growing in northern Italy, Pharm. Biol., 1990, 28, 219–223 http://dx.doi.org/10.3109/1388020900908281710.3109/13880209009082817Search in Google Scholar

[60] Dirsch V., Lacaille-Dubois M.-A., Wagner H., Dracoside, a new steroidal saponin from Helleborus purpurascens, Nat. Prod. Lett., 1994, 4, 29–33 http://dx.doi.org/10.1080/1057563940804388810.1080/10575639408043888Search in Google Scholar

[61] Meng Y., Whiting P., Šik V., Rees H. H., Dinan L., Ecdysteroids and bufadienolides from Helleborus torquatus (Ranunculaceae), Phytochemistry, 2001, 57, 401–407 http://dx.doi.org/10.1016/S0031-9422(01)00070-X10.1016/S0031-9422(01)00070-XSearch in Google Scholar

[62] Maleš Z., Medić-Šarić M., Optimization of TLC analysis of flavonoids and phenolic acids of Helleborus atrorubens Waldst. et Kit., J. Pharm. Biomed. Anal., 2001, 24, 353–359 http://dx.doi.org/10.1016/S0731-7085(00)00455-610.1016/S0731-7085(00)00455-6Search in Google Scholar

[63] Watanabe K., Mimaki Y., Sakuma C., Sashida Y., A novel polyoxygenated spirostanol trisdesmoside from the rhizomes of Helleborus orientalis, Chem. Lett., 2002, 31, 772–773 http://dx.doi.org/10.1246/cl.2002.77210.1246/cl.2002.772Search in Google Scholar

[64] Watanabe K., Mimaki Y., Sakagami H., Sashida Y., Bufadienolide and spirostanol glycosides from the rhizomes of Helleborus orientalis, J. Nat. Prod., 2003, 66, 236–241 http://dx.doi.org/10.1021/np020363810.1021/np0203638Search in Google Scholar PubMed

[65] Watanabe K., Sakagami H., Mimaki Y., Four new steroidal saponins from the rhizomes of Helleborus orientalis, Heterocycles, 2005, 65, 775–785 http://dx.doi.org/10.3987/COM-04-1031910.3987/COM-04-10319Search in Google Scholar

[66] Mimaki Y., Watanabe K., Sakuma C., Sakagami H., Sashida Y., Novel polyoxygenated spirostanol glycosides from the rhizomes of Helleborus orientalis, Helv. Chim. Acta, 2003, 86, 398–407 http://dx.doi.org/10.1002/hlca.20039004010.1002/hlca.200390040Search in Google Scholar

[67] Braca A., Prieto J.M., De Tommasi N., Tomè F., Morelli I., Furostanol saponins and quercetin glycosides from the leaves of Helleborus viridis L., Phytochemistry, 2004, 65, 2921–2928 http://dx.doi.org/10.1016/j.phytochem.2004.07.01310.1016/j.phytochem.2004.07.013Search in Google Scholar PubMed

[68] Akin S., Anil H., A furostanol saponin and phytoecdysteroid from roots of Helleborus orientalis, Chem. Nat. Compd., 2007, 43, 90–92 http://dx.doi.org/10.1007/s10600-007-0039-810.1007/s10600-007-0039-8Search in Google Scholar

[69] Prieto J.M., Siciliano T., Braca A., A new acylated quercetin glycoside and other secondary metabolites from Helleborus foetidus, Fitoterapia, 2006, 77, 203–207 http://dx.doi.org/10.1016/j.fitote.2006.01.01210.1016/j.fitote.2006.01.012Search in Google Scholar PubMed

[70] Muzashvili T.S., Benidze M.M., Skhirtladze A.V., Sulakvelidze Ts. P., Steroidal sapogenins from subterranean organs of Helleborus caucasicus, Chem. Nat. Compd., 2006, 42, 613 http://dx.doi.org/10.1007/s10600-006-0230-310.1007/s10600-006-0230-3Search in Google Scholar

[71] Bassarello C., Muzashvili T., Skhirtladze A., Kemertelidze E., Pizza C., Piacente S., Steroidal glycosides from the underground parts of Helleborus caucasicus, Phytochemistry, 2008, 69, 1227–1233 http://dx.doi.org/10.1016/j.phytochem.2007.11.00710.1016/j.phytochem.2007.11.007Search in Google Scholar PubMed

[72] Muzashvili T.S., Kemertelidze E.P., Steroidal compounds from Helleborus caucasicus leaves, Chem. Nat. Compd., 2009, 45, 925–926 http://dx.doi.org/10.1007/s10600-010-9460-510.1007/s10600-010-9460-5Search in Google Scholar

[73] Rosselli S., Maggio A., Bruno M., Spadaro V., Formisano C., Irace C., et al., Furostanol saponins and ecdysones with cytotoxic activity from Helleborus bocconei ssp. intermedius, Phytother. Res., 2009, 23, 1243–1249 http://dx.doi.org/10.1002/ptr.256910.1002/ptr.2569Search in Google Scholar PubMed

[74] Mimaki Y., Matsuo Y., Watanabe K., Sakagami H., Furostanol glycosides from the rhizomes of Helleborus orientalis, J. Nat. Med., 2010, 64, 452–459 http://dx.doi.org/10.1007/s11418-010-0432-710.1007/s11418-010-0432-7Search in Google Scholar PubMed

[75] Yang J., Zhang Y.-H., Miao F., Zhou L., Sun W., Two new bufadienolides from the rhizomes of Helleborus thibetanus Franch, Fitoterapia, 2010, 81, 636–639 http://dx.doi.org/10.1016/j.fitote.2010.03.00910.1016/j.fitote.2010.03.009Search in Google Scholar PubMed

[76] Yang F.-Y., Su Y.-F., Wang Y., Chai X., Han X., Wu Z.-H., et al., Bufadienolides and phytoecdysones from the rhizomes of Helleborus thibetanus (Ranunculaceae), Biochem. Sys. Ecol., 2010, 38, 759–763 http://dx.doi.org/10.1016/j.bse.2010.07.00210.1016/j.bse.2010.07.002Search in Google Scholar

[77] Stochmal A., Perrone A., Piacente S., Oleszek W., Saponins in aerial parts of Helleborus viridis L., Phytochem. Lett., 2010, 3, 129–132 http://dx.doi.org/10.1016/j.phytol.2010.04.00510.1016/j.phytol.2010.04.005Search in Google Scholar

[78] Muzashvili T., Perrone A., Napolitano A., Kemertelidze E., Pizza C., Piacente S., Caucasicosides E-M, furostanol glycosides from Helleborus caucasicus, Phytochemistry, 2011, 72, 2180–2188 http://dx.doi.org/10.1016/j.phytochem.2011.08.00810.1016/j.phytochem.2011.08.008Search in Google Scholar

[79] Vitalini S., Braca A., Fico G., Study on secondary metabolite content of Helleborus niger L. leaves, Fitoterapia, 2011, 82, 152–154 http://dx.doi.org/10.1016/j.fitote.2010.08.01210.1016/j.fitote.2010.08.012Search in Google Scholar

[80] Stec B., Plant thionins — the structural perspective, Cell. Mol. Life Sci., 2006, 63, 1370–1385 http://dx.doi.org/10.1007/s00018-005-5574-510.1007/s00018-005-5574-5Search in Google Scholar

[81] Milbradt A.G., Kerek F., Moroder L., Renner C., Structural Characterization of Hellethionins from Helleborus purpurascens, Biochemistry, 2003, 42, 2404–2411 http://dx.doi.org/10.1021/bi020628h10.1021/bi020628hSearch in Google Scholar

[82] Bhave M., Methuku D.R., Small cysteinerich proteins from plants: a rich resource of antimicrobial agents, In: Science against microbial pathogens: communicating current research and technological advances, Ed. A. Méndez-Vilas, 2011, 1074–1083 Search in Google Scholar

[83] Pelegrini P.B., Franco O.L., Plant γ-thionnins: Novel insights of the mechanism of action of the multi-functional class of defence proteins, Int. J. Biochem. Cell B., 2005, 37, 2239–2253 http://dx.doi.org/10.1016/j.biocel.2005.06.01110.1016/j.biocel.2005.06.011Search in Google Scholar

[84] Kerek F., Boicil, a new and very efficient antialgic, spasmolytic, and blood vessel regulating drug obtained from the plant Helleborus. First International Conference on Chemistry and Biochemistry of Biologically Active Natural Compounds (FECS, 1981), 2, 22–37 Search in Google Scholar

[85] Erdemoglu N., Küpeli E., Yeşilada E., Antiinflammatory and antinociceptive activity assessment of plants used as remedy in Turkish folk medicine, J. Ethnopharmacol., 2003, 89, 123–129 http://dx.doi.org/10.1016/S0378-8741(03)00282-410.1016/S0378-8741(03)00282-4Search in Google Scholar

[86] Nueleanu V.I., The effect of the unspecific therapy with hellebore (Helleborus purpurascens) on young sheep, Proceedings. Animal Husbandry. 43rd Croatian and 3rd International Symposium on Agriculture, (18–21 February 2008, Opatija, Croatia), 791–794 Search in Google Scholar

[87] Davidović V., Joksimović Todorović M., Stojanović B., Relić, R., Plant usage in protecting the farm animal health, Biotechnology in Animal Husbandry, 2012, 28, 87–98 http://dx.doi.org/10.2298/BAH1201087D10.2298/BAH1201087DSearch in Google Scholar

[88] Lupu A.R., MCS-18 — potential therapeutic agent in neuro-immunological pathology [MCS-18 — potential agent terapeutic in patologii neuroimune], Ph.D. Thesis, University of Bucharest, Faculty of Biology, Bucharest, Romania, 2009 (in Romanian) Search in Google Scholar

[89] Kerek F., Stimac R., Apell H.-J., Freudenmann F., Moroder L., Characterization of the macrocyclic carbon suboxide factors as potent Na, K-ATPase and SR Ca-ATPase inhibitors, Biochim. Biophys. Acta, 2002, 1567, 213–220 10.1016/S0005-2736(02)00609-0Search in Google Scholar

[90] Kerek F., The structure of the digitalis like and natriuretic factors identified as macrocyclic derivatives of the inorganic carbon suboxide, Hypertens. Res., 2000, 23, 33–38 http://dx.doi.org/10.1291/hypres.23.Supplement_S3310.1291/hypres.23.Supplement_S33Search in Google Scholar

[91] Szegli G., Herold A., Cremer L., Călugaru A., Matache C., Durbaca S., et al., Immunpharmacology studies on MCS-18, Investigational Medicinal Product Dossier, 2005, Part 2.2, 1–42 Search in Google Scholar

[92] Kerek F., Szegli G., Cremer L., Lupu A.R., Durbaca S., Călugaru A., et al., The novel arthritis drug-substance MCS-18 down-regulates in vivo antibody production, Acta Microbiol. Immunol. Hung., 2008, 55, 15–31 http://dx.doi.org/10.1556/AMicr.55.2008.1.210.1556/AMicr.55.2008.1.2Search in Google Scholar

[93] Neacşu C., Ciobanu C., Barbu I., Toader O., Szegli G., Kerek F., et al., Substance MCS-18 isolated from Helleborus purpurascens is a potent antagonist of the capsaicin receptor, TRPV1, in rat cultured sensory neurons, Physiol. Res., 2010, 59, 289–298 10.33549/physiolres.931658Search in Google Scholar

[94] Horstmann B., Zinser E., Turza N., Kerek F., Steinkasserer A., MCS-18, a novel natural product isolated from Helleborus purpurascens, inhibits dendritic cell activation and prevents autoimmunity as shown in vivo using the EAE model, Immunobiology, 2008, 212, 839–853 http://dx.doi.org/10.1016/j.imbio.2007.09.01610.1016/j.imbio.2007.09.016Search in Google Scholar

[95] Littmann L., Rößner S., Kerek F., Steinkasserer A., Zinser E., Modulation of murine bone marrowderived dendritic cells and B-cells by MCS-18 a natural product isolated from Helleborus purpurascens, Immunobiology, 2008, 213, 871–878 http://dx.doi.org/10.1016/j.imbio.2008.07.01310.1016/j.imbio.2008.07.013Search in Google Scholar

[96] Seifarth C., Littmann L., Resheq Y., Rößner S., Goldwich A., Pangratz N., et al., MCS-18, a novel natural plant product prevents autoimmune diabetes, Immunol. Lett., 2011, 139, 58–67 http://dx.doi.org/10.1016/j.imlet.2011.04.01610.1016/j.imlet.2011.04.016Search in Google Scholar

[97] Apetrei N.S., Lupu A.-R., Calugaru A., Kerek F., Szegli G., Cremer L., The antioxidant effects of some progressively purified fractions from Helleborus purpurascens, Rom. Biotechnol. Lett., 2011, 16, 6673–6681 Search in Google Scholar

[98] Păun-Roman G., Neagu E., Radu G.L., Membrane processes for the purification and concentration of Helleborus purpurascens extracts and evaluation of antioxidant activity, Rev. Chim. (Bucharest), 2010, 61, 877–881 Search in Google Scholar

[99] Čakar J., Parić A., Vidic D., Haverić A., Haverić S., Maksimović M., et al., Antioxidant and antiproliferative activities of Helleborus odorus Waldst. & Kit, H. multifidus Vis. and H. hercegovinus Martinis, Nat. Prod. Res., 2011, 25, 1969–1974 http://dx.doi.org/10.1080/14786419.2010.54187210.1080/14786419.2010.541872Search in Google Scholar

[100] Trenin D.S., Volodin V.V., 20-hydroxyecdysone as a human lymphocyte and neutrophil modulator: In vitro evaluation, Arch. Insect Biochem. Physiol., 1999, 41, 156–161 http://dx.doi.org/10.1002/(SICI)1520-6327(1999)41:3<156::AID-ARCH7>3.0.CO;2-Q10.1002/(SICI)1520-6327(1999)41:3<156::AID-ARCH7>3.0.CO;2-QSearch in Google Scholar

[101] Puglisi S., Speciale A., Acquaviva R., Ferlito G., Ragusa S., De Pasquale R., et al., Antibacterial activity of Helleborus bocconei Ten. subsp. siculus root extracts, J. Ethnopharmacol., 2009, 125, 175–177 http://dx.doi.org/10.1016/j.jep.2009.06.01110.1016/j.jep.2009.06.011Search in Google Scholar

[102] Rosselli S., Maggio A., Formisano C., Napolitano F., Senatore F., Spadaro V., et al., Chemical composition and antibacterial activity of extracts of Helleborus bocconei Ten. subsp. intermedius, Nat. Prod. Commun., 2007, 2, 675–679 10.1177/1934578X0700200611Search in Google Scholar

[103] Lindholm P., Gullbo J., Claeson P., Göransson U., Johansson S., Backlund A., et al., Selective cytotoxicity evaluation in anticancer drug screening of fractionated plant extracts, J. Biomol. Screen., 2002, 7, 333–340 http://dx.doi.org/10.1177/10870571020070040510.1177/108705710200700405Search in Google Scholar

[104] Muzashvili T., Skhirtladze A., Sulakvelidze T., Benidze M., Mshviladze V., Legault J., et al., Cytotoxic activity of Helleborus caucasicus A. Br., Georg. Chem. J., 2006, 6, 684–685 Search in Google Scholar

[105] Jesse P., Mottke G., Eberle J., Seifert G., Henze G., Prokop A., Apoptosis-inducing activity of Helleborus niger in ALL and AML, Pediatr. Blood Cancer, 2009, 52, 464–469 http://dx.doi.org/10.1002/pbc.2190510.1002/pbc.21905Search in Google Scholar

[106] Vochita G., Mihai C.T., Gherghel D., Iurea D., Roman G., Radu G.L., et al., New potential antitumoral agents of polyphenolic nature obtained from Helleborus purpurascens by membranary micro- and ultrafiltration techniques, SAAIC, 2011, 12, 41–51 Search in Google Scholar

[107] Büssing A., Schweizer K., Effects of a phytopreparation from Helleborus niger on immunocompetent cells in vitro, J. Ethnopharmacol., 1998, 59, 139–146 http://dx.doi.org/10.1016/S0378-8741(97)00114-110.1016/S0378-8741(97)00114-1Search in Google Scholar

[108] Smulders M.J.M., de Klerk G.J., Epigenetics in Plant Tissue Culture, J. Plant Growth Regul., 2011, 63 137–146 http://dx.doi.org/10.1007/s10725-010-9531-410.1007/s10725-010-9531-4Search in Google Scholar

[109] Grabowski K., Schneider G., Properties and Architecture of Drugs and Natural Products Revisited, Curr. Chem. Biol., 2007, 1, 115–127 10.2174/2212796810701010115Search in Google Scholar