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Biologically active compounds and pharmacological activities of species of the genus Crocus: A review

  • 1. ∗ & Department of Botany, National University of Pharmacy, 61168, Kharkiv, str. Valentynivska, 4, Ukraine

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Mykhailenko, Olga, Kovalyov, Volodymyr, Goryacha, Olga, Ivanauskas, Liudas, Georgiyants, Victoriya (2019): Biologically active compounds and pharmacological activities of species of the genus Crocus: A review. Phytochemistry 162: 56-89, DOI: 10.1016/j.phytochem.2019.02.004, URL: http://dx.doi.org/10.1016/j.phytochem.2019.02.004

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References

  • Abbasvali, M., Ranaei, A., Shekarforoush, S.S., Moshtaghi, H., 2016. The effects of aqueous and alcoholic saffron (Crocus sativus) tepal extracts on quality and shelf- life of pacific white shrimp (Litopeneous vannamei) during iced storage. J. Food Qual. 39, 732-742.
  • Abdullaev, F.I., Espinosa-Aguirre, J.J., 2004. Biomedical properties of saffron and its potential use in cancer therapy and chemoprevention trials. Cancer Detect. Prev. 28, 426-432.
  • Abdullaev, F.I., Frenkel, G.D., 1999. Saffron in Biological and Medical Research. Saffron: Crocus Sativus L. Harwood Academic Publishers, Australia, pp. 103-114.
  • Abedi, M.S., Pestechian, N., Ghanadian, M., Nateghpour, M., 2016. In vivo comparative study of antimalarial activity of hydro-alcoholic extract of Crocus sativus (stigma) with chloroquine. Sci. J. Sch. Publ. Health Inst. Publ. Health Res. 14, 81-90.
  • Acar, G., Dogan, N.M., Duru, M.E., Kivrak, I., 2010. Phenolic profiles, antimicrobial and antioxidant activity of the various extracts of Crocus species in Anatolia. Afr. J. Microbiol. Res. 4, 1154-1161.
  • Agayev, Y.M., Fernandez, J.-A., Zarifi, E., 2009. Clonal selection of saffron (Crocus sativus L.): the first optimistic experimental results. Euphytica 169, 81-99.
  • Agnihotri, V., 2015. Crocus sativus Linn.: an informative review. Aperito J. Advanced Plant Biology 1, 103-132.
  • Ahrazem, O., Rubio-Moraga, A., Nebauer, S.G., Molina, R.V., Gomez-Gomez, L., 2015a. Saffron: its phytochemistry, developmental processes, and biotechnological prospects. J. Agric. Food Chem. 63, 8751-8764.
  • Ahrazem, O., Rubio-Moraga, A., Jimeno, M.L., Gomez-Gomez, L., 2015b. Structural characterization of highly glucosylated crocins and regulation of their biosynthesis during flower development in Crocus. Front. Plant Sci. 6, 971-1006.
  • Akhondzadeh, B.A., Moshiri, E., Noorbala, A.A., Jamshidi, A.H., Abbasi, S.H., Akhondzadeh, S., 2007. Comparison of petal of Crocus sativus L. and fluoxetine in the treatment of depressed outpatients: a pilot double-blind randomized trial. Prog. Neuro-Psychopharmacol. Biol. Psychiatry 31, 439-442.
  • Alavizadeh, S.H., Hosseinzadeh, H., 2014. Bioactivity assessment and toxicity of crocin: a comprehensive review. Food Chem. Toxicol. 64, 65-80.
  • Alizadeh, F., Bolhassani, A., 2015. In vitro cytotoxicity of Iranian saffron and two main components as a potential anti-cancer drug. SM J. Pharmac. Ther. 1, 1001-1005.
  • Alonso, G.L., Salinas, M.R., Sanchez-Fernandez, M.A., Garijo, J., 2000. Physical parameters in controlling saffron quality. Food Sci. Technol. Int. 6, 59-65.
  • Alonso, G.L., Zalacain, A., Carmona, M., 2012. Saffron. In: Peter, K.V. (Ed.), Handbook of Herbs and Spices, second ed. Woodhead Publishing, Cambridge.
  • Asgarpanah, J., Darabi-Mahboub, E., Mahboubi, A., Mehrab, R., Hakemivala, M., 2013. In-vitro evaluation of Crocus sativus L. petals and stamens as natural antibacterial agents against food-borne bacterial strains. Iran. J. Pharm. Sci. 9, 69-82.
  • Assimiadis, M.K., Tarantilis, P.A., Polissiou, M.G., 1997. Characterization of cis-trans isomers of saffron carotenoids by UV-VIS, FT-Raman and 1 H NMR spectroscopies. In: Carmona, P., Navarro, R., Hernanz, A. (Eds.), Spectroscopy of Biological Molecules: Modern Trends. Springer, Dordrecht, Publisher Name Springer, Dordrecht, pp. 495-496.
  • Baba, S.A., Ashraf, N., 2016. Apocarotenoids of Crocus Sativus L: from Biosynthesis to Pharmacology. Springer, Singapore.
  • Baba, S.A., Malik, A.H., Wani, Z.A., Mohiuddin, T., Shah, Z., Abbas, N., Ashraf, N., 2015a. Phytochemical analysis and antioxidant activity of different tissue types of Crocus sativus and oxidative stress alleviating potential of saffron extract in plants, bacteria, and yeast. South Afr. J. Bot. 99, 80-87.
  • Baba, S.A., Mohiuddin, T., Basu, S., Swarnkar, M.K., Malik, A.H., Wani, Z.A., Abbas, N., Singh, A.K., Ashraf, N., 2015b. Comprehensive transcriptome analysis of Crocus sativus for discovery and expression of genes involved in apocarotenoid biosynthesis. BMC Genomics 16, 698-729.
  • Babaei, A., Arshami, J., Haghparast, A., Mesgaran, D.M., 2014. Effects of saffron (Crocus sativus) petal ethanolic extract on hematology, antibody response, and spleen histology in rats. Avicenna J. Phytomed. 4, 103-109.
  • Badie, B.H., Mehri, S., Hosseinzadeh, H., 2017. Toxicology effects of saffron and its constituents: a review. Iran J. Basic Med. Sci. 20, 110-121.
  • Bagri, J., Yadav, A., Anwar, Kh, Dkhar, J., Singla-Pareek, S.L., Pareek, A., 2017. Metabolic shift in sugars and amino acids regulates sprouting in Safron corm. Sci. Rep. 7, 11904-11914.
  • Bate-Smith, E.C., 1968. The phenolic constituents of plants and their taxonomic significance. J. Linn. Soc. (Bot.). 1617.
  • Behjat, J., Amirhossein, S., Seyed, A.E., 2013. A survey on saffron in major Islamic traditional medicine books. Iran J. Basic. Med. Sci. 16, 1-11.
  • Bhandari, P.R., 2015. Crocus sativus L. (saffron) for cancer chemoprevention: a mini review. J. Trad. Complem. Medic. 5, 81-87.
  • Bolhassani, A., Khavari, A., Bathaie, S.Z., 2014. Saffron and natural carotenoids: biochemical activities and anti-tumor effects. BBA Rev. Cancer 1845, 20-30.
  • Bononi, M., Milella, P., Tateo, F., 2015. Gas chromatography of safranal as preferable method for the commercial grading of saffron (Crocus sativus L.). Food Chem. 176, 17-21.
  • Boskabady, M.H., Farkhondeh, T., 2016. Antiinflammatory, antioxidant, and immunomodulatory effects of Crocus sativus L. and its main constituents. Phytother Res. 30, 1072-1094.
  • Bosser, A., Belin, J.M., 1994. Synthesis of β -ionone in an aldehyde/xanthine oxidase/β- carotene system involving free radical formation. Biotechnol. Prog. 10, 129-133.
  • Bouvier, F., Suire, C., Mutterer, J., Camara, B., 2003. Oxidative remodeling of chromoplast carotenoids: identification of the carotenoid dioxygenase CsCCD and CsZCD genes involved in Crocus secondary metabolite biogenesis. Plant Cell 15, 47-62.
  • Caballero-Ortega, H., Pereda-Miranda, R., Abdullaev, F.I., 2007. HPLC quantification of major active components from 11 different saffron (Crocus sativus L.) sources. Food Chem. 100, 1126-1131.
  • Carmona, M., Sanchez, A.M., Ferreres, F., Zalacain, A., Tomas-Barberan, F., Alonso, G., 2007. Identification of the flavonoid fraction in saffron spice by LC/DAD/MS/MS: comparative study of samples from different geographical origins. Food Chem. 100, 445-450.
  • Carmona, M., Zalacain, A., Salinas, M.R., Alonso, G.L., 2006a. Generation of saffron volatiles by thermal carotenoid degradation. J. Agric. Food Chem. 54, 6825-6834.
  • Carmona, M., Zalacain, A., Sanchez, A.M., Novella, J.L., Alonso, G.L., 2006b. Crocetin esters, picrocrocin and its related compounds present in Crocus sativus stigmas and Gardenia jasminoides fruits. Tentative identification of seven new compounds by LC-ESI-MS. J. Agric. Food Chem. 54, 973-979.
  • Carradori, S., Chimenti, P., Fazzari, M., Granese, A., Angiolella, L., 2016. Antimicrobial activity, synergism and inhibition of germ tube formation by Crocus sativus -derived compounds against Candida spp. J. Enzym. Inhib. Med. Chem. 31, 189-193.
  • Castillo, R., Fernandez, J.A., Gomez-Gomez, L., 2005. Implications of carotenoid biosynthetic genes in apocarotenoid formation during the stigma development of Crocus sativus and its closer relatives. Plant Physiol. 139, 674-689.
  • Chamkhi, I., Sbabou, L., Aurag, J., 2018. Endophytic fungi isolated from Crocus sativus L. (Saffron) as a source of bioactive secondary metabolites. Pharm. J. 10, 1143-1148.
  • Chen, B., Hou, Z.H., Dong, Z., Li, C.D., 2015. Crocetin downregulates the proinflammatory cytokines in methylcholanthrene-induced rodent tumor model and inhibits COX-2 expression in cervical cancer cells. BioMed Res. Int. 2015, 829513-882518.
  • Christodoulou, E., Kadoglou, N.P., Kostomitsopoulos, N., Valsami, G., 2015. Saffron: a natural product with potential pharmaceutical applications. J. Pharm. Pharmacol. 67, 1634-1649.
  • D'Archivio, A.A., Donato, F.D., Foschi, M., Maggi, M.A., Ruggieri, F., 2018. UHPLC analysis of saffron (Crocus sativus L.): optimization of separation using chemometrics and detection of minor crocetin esters. Molecules 23, 1851-1867.
  • D'Archivio, A.A., Giannitto, A., Incani, A., Nisi, S., 2014. Analysis of the mineral composition of Italian saffron by ICP-MS and classification of geographical origin. Food Chem. 157, 485-489.
  • Dawalbhakta, M., Telang, M., 2017. Patents on therapeutic and cosmetic applications of bioactives of Crocus sativus L. and their production through synthetic biology methods: a review. Pat. Biotechnol. 11, 3-19.
  • De Monte, C., Bizzarri, B., Gidaro, M.C., Carradori, S., Mollica, A., Luisi, G., Granese, A., Alcaro, S., Costa, G., Basilico, N., Parapini, S., Scaltrito, M.M., Masia, C., Sisto, F., 2015. Bioactive compounds of Crocus sativus L. and their semi-synthetic derivatives as promising anti-Helicobacter pylori, anti-malarial and anti-leishmanial agents. J. Enzym. Inhib. Med. Chem. 30, 1027-1033.
  • Del Campo, C.P., Garde-Cerdan, T., Sanchez, A.M., Maggi, L., Carmona, M., Alonso, G.L., 2009. Determination of free amino acids and ammonium ion in saffron (Crocus sativus L.) from different geographical origins. Food Chem. 114, 1542-1548.
  • Dufresne, C., Cormier, F., Dorion, S., Niggli, U.S., Pfister, S., Pfander, H., 1999. Glycosylation of encapsulated crocetin by a Crocus sativus L. cell culture. Enzym. Microb. Technol. 24, 453-462.
  • Escribano, J., Alonso, G.-L., Coca-Prados, M., Fernhdez, J.-A., 1996. Crocin, safranal and picrocrocin from saffron (Crocus sativus L.) inhibit the growth of human cancer cells in vitro. Cancer Lett. 100, 23-30.
  • Escribano, J., Diaz-Guerra, M.J., Riese, H.H., Alvarez, A., Proenza, R., Fernandez, J.A., 2000. The cytolytic effect of a glycoconjugate extracted from corms of saffron plant (Crocus sativus) on human cell lines in culture. Planta Med. 66, 157-162.
  • Esmaeili, N., Ebrahimzadeh, H., Abdi, K., Safarian, S., 2011. Determination of some phenolic compounds in Crocus sativus L. corms and its antioxidant activities study. Pharmacog. Mag. 7, 74-80.
  • Farjah, G.H., Salehi, S., Ansari, M.H., Pourheidar, B., 2017. Protective effect of Crocus sativus L. (Saffron) extract on spinal cord ischemia-reperfusion injury in rats. Iranian J. Basic Medical. Sci. 20, 334-337.
  • Feizy, J., Reyhani, N., 2016. Gas chromatographic determination of phytosterols and fatty acids profile in saffron petals. Can. Chem. Trans. 4, 389-397.
  • Fernandez, J.A., Escribano, J., Piqueras, A., Medina, J., 2000. A glycoconjugate from corms of saffron plant (Crocus sativus L.) inhibits root growth and affects in vitro cell viability. J. Exp. Bot. 51, 731-737.
  • Fernandez, J.A., Santana, O., Guardiola, J.L., Molina, R.V., Heslop-Harrison, P., et al., 2011. The world saffron and crocus collection: strategies for establishment, management, characterisation and utilisation. Genet. Resour. Crop Evol. 58, 125-137.
  • Fernandez-Sanchez, L., Lax, P., Esquiva, G., Martin-Nieto, J., Pinilla, I., Cuenca, N., 2012. Safranal, a saffron constituent, attenuates retinal degeneration in P23H rats. PLoS One 7, e43074.
  • Ferrara, L., Naviglio, D., Gallo, M., 2014. Extraction of bioactive compounds of saffron (Crocus sativus L.) by ultrasound assisted extraction (uae) and by rapid solid-liquid dynamic extraction (rslde). Eur. Sci. J. 3, 1-13.
  • Finley, J.W., Gao, S.A., 2017. Perspective on Crocus sativus L. (saffron) constituent crocin: a potent water-soluble antioxidant and potential therapy for Alzheimer's disease. J. Agric. Food Chem. 65, 1005-1020.
  • Gao, W.Y., Li, Y.M., Zhu, D.Y., 1999a. Phenolic glucosides and a γ -lactone glucoside from the sprouts of Crocus sativus. Planta Med. 65, 425-427.
  • Gao, W.Y., Li, Y.M., Zhu, D.Y., 1999b. New anthraquinones from the sprout of Crocus sativus. Acta Bot. Sin. 41, 531-533.
  • Tarantilis, P.A., 2017. Comparative evaluation of an ISO 3632 method and an HPLC- DAD method for safranal quantity determination in saffron. Food Chem. 221, 838-843.
  • Ghosal, S., Singh, S.K., Battacharya, S.K., 1989. Mangicrocin, and adaptogenic xanthone-carotenoid glycosidic conjugate from saffron. J. Chem. Researh. 3, 70-77.
  • Giorgi, A., Pentimalli, D., Giupponi, L., Panseri, S., 2017. Quality traits of saffron (Crocus sativus L.) produced in the Italian Alps. Open Agriculture 2, 52-57.
  • Gismondi, A., Serio, M., Canuti, L., Canini, A., 2012. Biochemical, antioxidant and antineoplastic properties of Italian saffron (Crocus sativus L.). Am. J. Plant Sci. 3, 1573-1580.
  • Gohari, A.R., Saeidnia, S., Mahmoodabadi, M.K., 2013. An overview on saffron, phytochemicals, and medicinal properties. Pharm. Rev. 7, 61-66.
  • Goli, S.A.H., Mokhtari, F., Rahimmalek, M., 2012. Phenolic compounds and antioxidant activity from saffron (Crocus sativus L.) petal. J. Agric. Sci. 4, 175-181.
  • Goupy, P., Vian, M.A., Chemat, F., Caris-Veyrat, C., 2013. Identification and quantification of flavonols, anthocyanins and lutein diesters in tepals of Crocus sativus by ultraperformance liquid chromatography coupled to diode array and ion trap mass spectrometry detections. Ind. Crops Prod. 44, 496-510.
  • Granchi, C., Fortunato, S., Meini, S., Rizzolio, F., Caligiuri, I., Tuccinardi, T., Lee, H.Y., Hergenrother, P.J., Minutolo, F., 2017. Characterization of the saffron derivative crocetin as an inhibitor of human lactate dehydrogenase 5 in the antiglycolytic approach against cancer. J. Agric. Food Chem. 65, 5639-5649.
  • Gregory, M.J., Menary, R.C., Davies, N.W., 2005. Effect of drying temperature and air flow on the production and retention of secondary metabolites in saffron. J. Agric. Food Chem. 53, 5969-5975.
  • Gresta, F., Avola, G., Lombardo, G.M., Siracusa, L., Ruberto, G., 2009. Analysis of flowering, stigmas yield and qualitative traits of saffron (Crocus sativus L.) as affected by environmental conditions. Sci. Hortic. 119, 320-324.
  • Gresta, F., Lombardo, G.M., Siracusa, L., Ruberto, G., 2008. Saffron, an alternative crop for sustainable agricultural systems. A review. 28. Springer Verlag/EDP Sciences/ INRA. Agron. Sustain. Dev., pp. 95-112.
  • Grosso, C., 2016. In: Grosso, Clara, Andrade, P., Catarino, L., Cheesman, M.J., Zhang, Ch (Eds.), Herbal Medicine in Depression: Traditional Medicine to Innovative Drug Delivery, first ed.st. Springer International Publishing, New York, pp. 292.
  • Hadizadeh, F., Khalili, N., Hosseinzadeh, H., Khair-Aldine, R., 2010. Kaempferol from saffron petals. Iran J. Pharm. Res. 2, 251-252.
  • Harborne, J.B., Williams, C.A., 1984. 6-Hydroxyflavones and other flavonoids of Crocus. Z. Naturforsch. 39c, 18-23.
  • Harborne, J.B., Williams, C.A., 2000. The phytochemical richness of the Iridaceae and its systematic significance. Ann. Bot. 58, 43-50.
  • Hashemi, P., Erim, F.B., 2016. Analysis of vitamin B2 in saffron stigmas (Crocus sativus L) by capillary electrophoresis coupled with laser-induced fluorescence detector. Food Anal. Methods. 9, 2395-2399.
  • Hassanin, A., 2015. Evaluation of the diuretic effects of crocin (active constituent of saffron) in rats. Int. J. Pharm. Biol. Sci. 6, 279-284.
  • Hoshyara, R., Mollaei, H., 2017. A comprehensive review on anticancer mechanisms of the main carotenoid of saffron, crocin. J. Pharm. Pharmacol. 69, 1419-1427.
  • Hosseini, A., Razavi, B.M., Hosseinzadeh, H., 2018. Saffron (Crocus sativus) petal as a new pharmacological target: a review. Iran. J. Basic. Med. Sci. 21, 1091-1099.
  • Hosseinzadeh, H., Younesi, H.M., 2002. Antinocicetive and anti-inflamatory effects of Crocus sativus L. stigma and petals extracts in mice. BMC Pharmacol. 2, 1-8.
  • Hu, J., Fang, L., Wang, R., Wang, P., 2015. The influence of different drying methods on constituents and antioxidant activity of saffron from China. Int. J. Anal. Chem 2015, 1-8 953164.
  • Imenshahidi, M., Hosseinzadeh, H., Javadpour, Y., 2010. Hypotensive effect of aqueous saffron extract (Crocus sativus L.) and its constituents, safranal and crocin, in normotensive and hypertensive rats. Phytoter. Res. 24, 990-994.
  • ISO 3632-1:2011, 2011. Spices - Saffron (Crocus Sativus L.), 2 Ed. International Organization for Standardization Geneve, Switzerland, pp. 6 Part 1: Specification.
  • ISO 3632-2:2010, 2010. Spices - Saffron (Crocus Sativus L.), 1 Ed. International Organization for Standardization Geneve, Switzerland, pp. 42 Part 2: Test methods.
  • Jabini, R., Ehtesham-Gharaee, M., Dalirsani, Z., Mosaffa, F., Delavarian, Z., Behravan, J., 2017. Evaluation of the cytotoxic activity of crocin and safranal, constituents of saffron, in oral squamous cell carcinoma (KB Cell Line). Nutr. Canc. 69, 911-919.
  • Jadouali, S.M., Atifi, H., Bouzoubaa, Z., Majourhat, K., Gharby, S., Achemchem, F., Elmoslih, A., Laknifli, A., Mamouni, R., 2018a. Chemical characterization, antioxidant and antibacterial activity of Moroccan Crocus sativus L. petals and leaves. J. Mater. Environ. Sci. 9, 113-118.
  • Jadouali, S.M., Atifi, H., Mamouni, R., Majourhat, K., Bouzoubaa, Z., Laknifli, A., Faouzi, A., 2018b. Chemical characterization and antioxidant compounds of flower parts of Moroccan Crocus sativus L. J. Saudi Soc. Agricult. Sci (Article (in press).
  • Jose, B.M., Alonso, S.G.L., Jimenez-Monreal, A.M., Chaouqi, S., Llorens, S., Martinez-Tome, M., Alonso, G.L., 2018. Saffron: an old medicinal plant and a potential novel functional food. Molecules 23, 30-51.
  • Kanakis, C.D., Daferera, D.J., Tarantilis, P.A., Polissiou, M.G., 2004. Qualitative determination of volatile compounds and quantitative evaluation of safranal and 4- hydroxy-2,6,6-trimethyl-1-cyclohexene-1-carboxaldehyde (HTCC) in Greek saffron. J. Agric. Food Chem. 52, 4515-4521.
  • Karabagias, I.K., Koutsoumpou, M., Liakou, V., Kontakos, S., Kontominas, M.G., 2017. Characterization and geographical discrimination of saffron from Greece, Spain, Iran, and Morocco based on volatile and bioactivity markers, using chemometrics. Eur. Food Res. Technol. 243, 1577-1591.
  • Karimi, E., Oskoueian, E., Hendra, R., Jaafar, H.Z., 2010. Evaluation of Crocus sativus L. stigma phenolic and flavonoid compounds and its antioxidant activity. Molecules 15, 6244-6256.
  • Kermani, T., Kazemi, T., Molki, S., Ilkhani, K., Sharifzadeh, G., Rajabi, O., 2017. The efficacy of crocin of saffron (Crocus sativus L.) on the components of metabolic syndrome: a randomized controlled clinical trial. J. Res. Pharm. Pract. 6, 228-232.
  • Khare, C.P., 2007. Indian Medicinal Plants. Springer-Verlag, Berlin: Heidelberg.
  • Khazaei, K.M., Jafari, S.M., Ghorbani, M., Kakhki, A.H., Sarfarazi, M., 2016. Optimization of anthocyanin extraction from saffron petals with response surface methodology. Food Anal. Methods. 9, 1993-2001.
  • Khazdair, M.R., Boskabady, M.H., Hosseini, M., Rezaee, R., Tsatsakis, M.A., 2015. The effects of Crocus sativus (saffron) and its constituents on nervous system: a review. Avicenna J. Phytom. 5, 376-391.
  • Kianbakht, S., Mozaffari, K., 2009. Effects of saffron and its active constituents, crocin and safranal, on prevention of indomethacin induced gastric ulcers in diabetic and nondiabetic rats. J. Med. Plants. 8, 30-38.
  • Kim, S.H., Lee, J.M., Kim, S.C., Park, C.B., Lee, P.C., 2014. Proposed cytotoxic mechanisms of the saffron carotenoids crocin and crocetin on cancer cell lines. Biochem. Cell Biol. 92, 105-111.
  • Kubo, I., Kinst-Hori, I., 1999. Flavonols from saffron flower: tyrosinase inhibitory activity and inhibition mechanism. J. Agric. Food Chem. 47 (10), 4121-4125.
  • Kumar, R., Singh, V., Devi, K., Sharma, M., Singh, M.K., Ahuja, P.S., 2009. State of art of saffron (Crocus sativus L.) agronomy: a comprehensive review. Food Rev. Int. 25, 44-85.
  • Kyriakoudi, A., Chrysanthou, A., Mantzouridou, F., Tsimidou, M.Z., 2012. Revisiting extraction of bioactive apocarotenoids from Crocus sativus L. dry stigmas (saffron). Anal. Chim. Acta 755, 77-85.
  • Lage, M., Cantrell, C., 2009. Quantification of saffron (Crocus sativus L.) metabolites crocins, picrocrocin and safranal for quality determination of the spice grown under different environmental Moroccan conditions. Sci. Hortic. 121, 366-373.
  • Lage, M., Melai, B., Cioni, P.L., Flamini, G., Gaboun, F., Bakhy, K., Zouahri, A., Pistelli, L., 2015. Phytochemical composition of Moroccan saffron accessions by headspace solidphase-microextraction. Am. J. Essential Oils Nat. Prod. 2, 1-7.
  • Lahmass, I., Ouahhoud, S., Elmansuri, M., Sabouni, A., Elyoubi, M., Benabbas, R., Choukri, M., Saalaoui, E., 2018. Waste Biomass. Valor. 9, 1349-1357.
  • Lari, P., Abnous, K., Imenshahidi, M., Rashedinia, M., Razavi, M., Hosseinzadeh, H., 2015. Evaluation of diazinon-induced hepatotoxicity and protective effects of crocin. Toxicol. Ind. Health 31, 367-376.
  • Leffingwell, J.C., 2002. Saffron. Leffing Well Reports 2, 1-3.
  • Li, C.Y., Lee, E.J., Wu, T.S., 2004. Antityrosinase principles and constituents of the petals of Crocus sativus. J. Nat. Prod. 67, 437-440.
  • Li, C.Y., Wu, T.S., 2002a. Constituents of the stigmas of Crocus sativus and their tyrosinase inhibitory activity. J. Nat. Prod. 65, 1452-1456.
  • Li, C.Y., Wu, T.S., 2002b. Constituents of the pollen of Crocus sativus L. and their tyrosinase inhibitory activity. Chem. Pharm. Bull. 50, 1305-1309.
  • Liakopoulou-Kyriakides, M., Kyriakidis, D.A., 2002. Crocus sativus - biological active constituents. Stud. Nat. Prod. Chem. 26G, 293-312.
  • Lim, T.K., 2014. Edible Medicinal and Non Medicinal Plants. Flowers. Crocus Sativus, vol. 8. Springer Netherlands, New York, London, pp. 77-136.
  • Llorens, S., Mancini, A., Serrano-Diaz, J., D'Alessandro, A.M., Nava, E., Alonso, G.L., Carmona, M., 2015. Effects of crocetin esters and crocetin from Crocus sativus L. on aortic contractility in rat genetic hypertension. Molecules 20, 17570-17584.
  • Loizzo, M.R., Marrelli, M., Pugliese, A., Conforti, F., Nadjafi, F., Menichini, F., Tundis, R., 2016. Crocus cancellatus subsp. damascenus stigmas: chemical profile, and inhibition of α -amylase, α- glucosidase and lipase, key enzymes related to type 2 diabetes and obesity. J. Enzym. Inhib. Med. Chem. 31, 212-218.
  • Lotfi, L., Kalbasi-Ashtari, A., Hamedi, M., Ghorbani, F., 2015. Effects of enzymatic extraction on anthocyanins yield of saffron tepals (Crocos sativus) along with its color properties and structural stability. J. Food Drug Anal. 23, 210-218.
  • Lozano, P., Delgado, D., Gomez, D., Rubio, M., Iborra, J.L., 2000. A nondestructive method to determine the safranal content of saffron (Crocus sativus L.) by supercritical carbon dioxide extraction combined with high-performance liquid chromatography and gas chromatography. J. Biochem. Biophys. Methods 43, 367-378.
  • Maggi, L., Carmona, M., Zalacain, A., Kanakis, C.D., Anastasaki, B.E., Tarantilis, P., et al., 2010. Changes in saffron volatile profile according to its storage time. Food Res. Int. 43, 1329-1334.
  • Makhlouf, H., Diab-Assaf, M., Alghabsha, M., Tannoury, M., Chahine, R., Saab, A.M., 2016. In vitro antiproliferative activity of saffron extracts against human acute lymphoblastic T-cell human leukemia. Indian J. Trad. Knowl. 15, 16-21.
  • Mancini, A., Serrano-Diaz, J., Nava, E., D'Alessandro, A.M., Alonso, G.L., Carmona, M., Liorens, S., 2014. Crocetin, a carotenoid derived from saffron (Crocus sativus L.), improves acetylcholine-induced vascular relaxation in hypertension. J. Vasc. Res. 51, 393-404.
  • Manthey, J.A., Guthrie, N., 2002. Antiproliferative activities of citrus flavonoids against six human cancer cell lines. J. Agric. Food Chem. 50, 5837-5843.
  • Manzo, A., Panseri, S., Bertoni, D., Giorgi, A., 2015. Economic and qualitative traits of Italian Alps saffron. J. Mountain Sci. 12, 1542-1550.
  • Mashmoul, M., Azlan, A., Khaza' ai, H., Mohd, Y.B.N., Mohd, N.S., 2013. Saffron: a natural potent antioxidant as a promising anti-obesity drug. Antioxidants 2, 293-308.
  • Masuda, A., Mori, K., Miyazawa, M., 2012. Comparative analysis of volatile compounds from corms of Crocus sativus and C. vernus. Chem. Nat. Comp. 48, 319-321.
  • McGimpsey, J.A., Douglas, M.H., Wallace, A.R., 1997. Evaluation of saffron (Crocus sativus L.) production in New Zealand. N. Z. J. Crop Hortic. Sci. 25, 159-168.
  • Middleton, E.J., 1998. Effect of plant flavonoids on immune and inflammatory cell function. Adv. Exp. Med. Biol. 439, 175-182.
  • Milajerdi, A., Djafarian, K., Hosseini, B., 2016. The toxicity of saffron (Crocus sativus L.) and its constituents against normal and cancer cells. J. Nutr. Interm. Metab. 3, 23-32.
  • Mir, J.I., Ahmed, N., Wafai, A.H., Qadri, R.A., 2012. Relative expression of CsZCD gene and apocarotenoid biosynthesis during stigma development in Crocus sativus. L. Physiol. Mol. Biol. Plants. 18, 371-375.
  • Mokhtari-Zaer, A., Khazdair, M.R., Boskabady, M.H., 2015. Smooth muscle relaxant activity of Crocus sativus (saffron) and its constituents: possible mechanisms. Avicenna J. Phytomed. 5, 365-375.
  • Montoro, P., Maldini, M., Luciani, L., Tuberoso, C.I., Congiu, F., Pizza, C., 2012. Radical scavenging activity and LC-MS metabolic profiling of petals, stamens, and flowers of Crocus sativus L. J. Food Sci. 77, 893-900.
  • Montoro, P., Tuberoso, C.I.G., Maldini, M., Cabras, P., Pizza, C., 2008. Qualitative profile and quantitative determination of flavonoids from Crocus sativus L. petals by LC-MS/ M. Nat. Prod. Commun. 3 2013-2016.
  • Moraga, A.R., Mozos, A.T., Ahrazem, O., Gomez-Gomez, L., 2009a. Cloning and characterization of a glucosyltransferase from Crocus sativus stigmas involved in flavonoid glucosylation. BMC Plant Biol. 9, 109.
  • Moraga, A.R., Rambla, J.L., Ahrazem, O., Granell, A., Gomez-Gomez, L., 2009b. Metabolite and target transcript analyses during Crocus sativus stigma development. Phytochemistry 70, 1009-1016.
  • Moshiri, E., Akhondzadeh, B.A., Noorbala, A.A., Jamshidi, A.-H., Hesameddin, S.A., Akhondzadeh, S., 2006. Crocus sativus L. (petal) in the treatment of mild-to-moderate depression: a double-blind, randomized and placebo-controlled trial. Phytomedicine 13, 607-611.
  • Mousavi, B., Bathaie, S.Z., Fadai, F., Ashtari, Z., Ali, B.N., Farhang, S., Hashempour, S., Shahhamzei, N., Heidarzadeh, H., 2015. Safety evaluation of saffron stigma (Crocus sativus L.) aqueous extract and crocin in patients with schizophrenia. Avicenna J. Phytomed. 5, 413-419.
  • Mousavi, M., Baharara, J., 2014. Effect of Crocus sativus L. on expression of VEGF-A and VEGFR-2 genes (angiogenic biomarkers) in MCF-7 cell line. Zahedan J. Res. Med. Sci. 16, 8-14.
  • Nasiri, Z., Sameni, H.R., Vakili, A., Jarrahi, M., Khorasani, M.Z., 2015. Dietary saffron reduced the blood pressure and prevented remodeling of the aorta in L-NAME-induced hypertensive rats. Iran. J. Basic. Med. Sci. 18, 1143-1146.
  • Noorbala, A.A., Akhondzadeh, S., Tahmacebi-Pour, N., Jamshidi, A.H., 2005. Hydro-alcoholic extract of Crocus sativus L. versus fluoxetine in the treatment of mild to moderate depression: a double-blind, randomized pilot trial. J. Ethnopharmacol. 97, 281-284.
  • Norbaek, R., Brandt, K., Nielsen, J.K., Orgaard, M., Jacobsen, N., 2002. Flower pigment composition of Crocus species and cultivars used for a chemotaxonomic investigation. Biochem. Syst. Ecol. 30, 763-791.
  • Norbaek, R., Kondo, T., 1998. Anthocyanins from flowers of crocus (Iridaceae). Phytochemistry 47, 861-864.
  • Norbaek, R., Kondo, T., 1999a. Further anthocyanins from flowers of Crocus antalyensis (Iridaceae). Phytochemistry 50, 325-328.
  • Norbaek, R., Kondo, T., 1999b. Flavonol glycosides from flowers of Crocus speciosus and C. antalyensis. Phytochemistry 51, 1113-1119.
  • Norbak, R., Nielsen, J., Kondo, T., 1999. Flavonoids from flowers of two Crocus chrysanthus-bi fl orus cultivars: "Eye-catcher" and "spring pearl" (Iridaceae). Phytochemistry 51 (8), 1139-1146.
  • Ordoudi, S.A., Tsimidou, M.Z., 2004. Saffron quality: effect of agricultural practices, processing and storage. In: Dris, R., Jain, S.M. (Eds.), Production Practices and Quality Assessment of Food Crops, 1. Springer, Dordrecht.
  • Papandreou, M.A., Kanakis, C.D., Polissiou, M.G., Efthimiopoulos, S., Cordopatis, P., Margarity, M., Lamari, F.N., 2006. Inhibitory activity on amyloid- β aggregation and antioxidant properties of Crocus sativus stigmas extract and its crocin constituents. J. Agric. Food Chem. 54, 8762-8768.
  • Parray, J.A., Kamili, A.N., Hamid, R., Reshi, Z.A., Qadri, R.A., 2015. Antibacterial and antioxidant activity of methanol extracts of Crocus sativus L. c.v. Kashmirianus. Front. Life Sci. 8, 40-46.
  • Patel, S., Sarwat, M., Khan, T.H., 2017. Mechanism behind the anti-tumour potential of saffron (Crocus sativus L.): the molecular perspective. Crit. Rev. Oncol. Hematol. 115, 27-35.
  • Pestechian, N., Abedi-Madiseh, S., Ghanadian, M., Nateghpour, M., 2015. Effect of Crocus sativus Stigma (saffron) alone or in combination with chloroquine on chloroquine sensitive strain of Plasmodium berghei in mice. J. Herb. Med. Pharmacol. 4, 110-114.
  • Pfander, H., Schurtenberger, H., 1982. Biosynthesis of C20-carotenoids in Crocus sativus L. Phytochemistry 21, 1039-1042.
  • Pfander, H., Wittwer, F., 1975. Carotinoid-glykoside 2. Mitteilung untersuchungen zur carotinoidzusammensetzung im safran. (Carotenoid-glycosides. Investigation of carotenoid-composition of saffron). Helv. Chim. Acta 58, 1608-1620 (in German).
  • Pfister, S., Meyer, P., Steck, A., Pfander, H., 1996. Isolation and structure elucidation of carotenoid glycosyl esters in Gardenia fruits (Gardenia jasminoides) and saffron (Crocus sativus Linn.). J. Agric. Food Chem. 44, 2119-2122.
  • Pitsikas, N., 2016. Constituents of saffron (Crocus sativus L.) as potential candidates for the treatment of anxiety disorders and schizophrenia. Molecules 21, 303-314.
  • Razavi, B.M., Hosseinzadeh, H., 2017. Saffron: a promising natural medicine in the treatment of metabolic syndrome. J. Sci. Food Agric. 97, 1679-1685.
  • Rios, J.L., Recio, M.C., Giner, R.M., Manets, S., 1996. An update review of saffron and its active constituents. Phytother Res. 10, 189-193.
  • Rubio, A., Rambla, J.L., Santaella, M., Gomez, M.D., Orzaez, D., Granell, A., Gomez-Gomez, L., 2008. Cytosolic and plastoglobule-targeted carotenoid dioxygenases from Crocus sativus are both involved in beta-ionone release. J. Biol. Chem. 283, 24816-24825.
  • Rubio-Moraga, A., Gerwig, G.J., Castro-Diaz, N., Jimeno, M.L., Escribano, J., Fernandez, J.A., Kamerling, J.P., 2011. Triterpenoid saponins from corms of Crocus sativus: localization, extraction and characterization. Ind. Crops Prod. 34, 1401-1409.
  • Rubio-Moraga, A., Gomez-Gomez, L., Trapero, A., Castro-Diaz, N., Ahrazem, O., 2013. Saffron corm as a natural source of fungicides: the role of saponins in the underground. Ind.Crop. Prod. 49, 915-921.
  • Rychener, M., Bigler, P., Pfander, H., 1984. Isolierung und strukturaufklarung von neapolitanose (O- β -D-glucopyranosyl-(1→2)-O-[β -D-glucopyranosyl-(1→6)]-(D-glucose), einem neuen trisaccharid aus den stempeln von gartenkrokussen (Crocus neapolitanus var.). Helv. Chem. Acta. 67, 386-391.
  • Samarghandian, S., Azimi-Nezhad, M., Farkhondeh, T., 2017. Immunomodulatory and antioxidant effects of saffron aqueous extract (Crocus sativus L.) on streptozotocininduced diabetes in rats. Indian Heart J. 69, 151-159.
  • Samarghandian, S., Azimi-Nezhad, M., Samini, F., 2014b. Ameliorative effect of saffron aqueous extract on hyperglycemia, hyperlipidemia, and oxidative stress on diabetic encephalopathy in streptozotocin induced experimental diabetes mellitus. Hindawi Publishing Corporation. BioMed Res. Int. 2014, 1-12 920857.
  • Samarghandian, S., Borji, A., 2014. Anticarcinogenic effect of saffron (Crocus sativus L.) and its ingredients. Pharma Res. 6, 99-107.
  • Samarghandian, S., Shoshtari, M.E., Sargolzaei, J., Hossinimoghadam, H., Farahzad, J.A., 2014a. Anti-tumor activity of safranal against neuroblastoma cells. Phcog. Mag. 10, 419-424.
  • Sanchez-Vioque, R., Rodriguez-Conde, M.F., Reina-Urena, J.V., Escolano-Tercero, M.A., Herraiz-Penalver, D., Santana-Meridas, O., 2012. In vitro antioxidant and metal chelating properties of corm, tepal and leaf from saffron (Crocus sativus L.). Ind. Crops Prod. 39, 149-153.
  • Sanchez-Vioque, R., Santana-Meridas, O., Polissiou, M., Vioque, J., Astraka, K., Alaizd, M., Herraiz-Penalvera, D., Tarantilis, P.A., Giron-Calle, J., 2016. Polyphenol composition and in vitro antiproliferative effect of corm, tepal and leaf from Crocus sativus L. on human colon adenocarcinoma cells (Caco-2). J. Funct. Foods 24, 18-25.
  • Sani, A.M., Kakhki, A.H., Moradi, E., 2013. Chemical composition and nutritional value of saffron's pollen (Crocus sativus L.). Nut. Food Sci. (N. Y.) 43, 490-495.
  • Santana-Meridas, O., Gonzalez-Coloma, A., Sanchez-Vioque, R., 2012. Agricultural residues as a source of bioactive natural products. Phytochemistry Rev.: Proc. Phytochem. Soc. Eur. 11, 447-466.
  • Satybaldiyeva, D., Mursaliyeva, V., Mammadov, R., Zayadan, B., 2016. Phenolic profiles and brine shrimp cytotoxicity of the ethanolic extract from the aerial part of Crocus alatavicus L. Int. J. Biol. Chem. 9, 38-41.
  • Satybaldiyeva, D., Mursaliyeva, V., Rakhimbayev, I., Zayadan, B., Mammadov, R., 2015. Preliminary phytochemical analysis and antioxidant, antibacterial activities of Crocus alatavicus from Kazakhstan. Not. Bot. Horti Agrobot. Cluj-Napoca 43, 343-348.
  • Serrano-Diaz, J., Sanchez, A.M., Alvarruiz, A., Alonso, G.L., 2013a. Preservation of saffron floral bio-residues by hot air convection. Food Chem. 141, 1536-1543.
  • Serrano-Diaz, J., Sanchez, A.M., Maggi, L., Martinez-Tome, M., Garcia-Diz, L., Murcia, M.A., Alonso, G.L., 2012. Increasing the applications of Crocus sativus flowers as natural antioxidants. J. Food Sci. 77, C1162-C1168.
  • Serrano-Diaz, J., Sanchez, A.M., Martinez-Tome, M., Winterhalter, P., Alonso, G.L., 2013b. A contribution to nutritional studies on Crocus sativus flowers and their value as food. J. Food Compos. Anal. 31, 101-108.
  • Shariatifar, N., Shoeibi, S., Sani, M.J., Jamshidi, A.H., Zarei, A.A., Mehdizade, A., Dadgarnejad, M., 2014a. Study on diuretic activity of saffron (stigma of Crocus sativus L.) aqueous extract in rat. J. Adv. Pharm. Technol. Research 5, 17-20.
  • Shariatifar, N., Shoeibi, S., Sani, M.J., Jamshidi, A.H., Zarei, A., Mehdizade, A., Dadgarnejad, M., 2014b. Study on diuretic activity of saffron (stigma of Crocus sativus L.) aqueous extract in rat. J. Adv. Pharm. Technol. Research 5, 17-20.
  • Singab, A.N.B., Ayoub, I.M., El-Shazly, M., Korinek, M., Wu, T.Y., Cheng, Y.B., Chang, F.R., Wu, Y.C., 2016. Shedding the light on Iridaceae: ethnobotany, phytochemistry and biological activity. Ind. Crops Prod. 92, 308-335.
  • Singleton, V., Rossi, J.A., 1965. Colorimetry of total phenolics with phosphomolybdicphosphotungstic acid reagents. Am. J. Enol. Vitic. 16, 144-158.
  • Smolskaite, L., Talou, T., Fabre, N., Venskutonis, P.R., 2011. Valorization of saffron industry by-products: bioactive compounds from leaves. Proceedings of the 6th baltic conference on food science and technology FOODBALT-2011, (jelgava, Latvia, may 5-6). In: Straumite, E. (Ed.), Innovations for Food Science and Production. Riga, Latvia. Faculty of Food Technology, pp. 67-72.
  • Song, C.Q., 1990. Chemical constituents of saffron (Crocus sativus). II. The flavonol compounds of petals. Zhong Cao Yao 2, 439-441.
  • Song, C.Q., Xu, R.S., 1991. Studies on the constituents of Crocus sativus III. The structural elucidation of two new glycosides of pollen. Acta Chem. Sinica. 49, 917-992.
  • Speranza, G., Dada, G., Manitto, P., Monti, D., Grammatica, P., 1984. 13-Cis crocin: a new crocinoid of saffron. Gazz. Chim. Ital. 114, 189-192.
  • Straubinger, M., Bau, B., Eckstein, S., Fink, M., Winterhalter, P., 1998. Identification of novel glycosidic aroma precursors in saffron (Crocus sativus L.). J. Agric. Food Chem. 46, 3238-3243.
  • Straubinger, M., Jezussek, M., Waibel, R., Winterhalter, P., 1997a. Two kaempferol sophorosides from Crocus sativus. Nat. Prod. Lett. 10, 213-216.
  • Straubinger, M., Jezussek, M., Waibel, R., Winterhalter, P., 1997b. Novel glycosidic constituents from saffron. J. Agric. Food Chem. 45, 1678-1681.
  • Tarantilis, P.A., Polissiou, M., Manfait, M., 1994. Separation of picrocrocin, cis-trans - crocins and safranal of saffron using high-performance liquid chromatography with photodiode-array detection. J. Chromatogr. A 664, 55-61.
  • Tarantilis, P.A., Polissiou, M.G., 1997. Isolation and identification of the aroma components from saffron (Crocus sativus). J. Agric. Food Chem. 45, 459-462.
  • Tarantilis, P.A., Tsoupras, G., Polissiou, M., 1995. Determination of saffron (Crocus sativus L.) components in crude plant extract using high-performance liquid chromatography-UV-visible photodiode-array detection-mass spectrometry. J. Chromatogr. A 699, 107-118.
  • Termentzi, A., Kokkalou, E., 2008. LC-DAD-MS (ESI+) analysis and antioxidant capacity of Crocus sativus petal extracts. Planta Med. 74, 573-581.
  • Tong, Y., Yan, Y., Zhu, X., Liu, R., Gong, F., Zhang, L., Wang, P., 2015. Simultaneous quantification of crocetin esters and picrocrocin changes in Chinese saffron by high-performance liquid chromatography-diode array detector during 15 years of storage. Phcog. Mag. 11, 540-545.
  • Trapero, A., Ahrazem, O., Rubio-Moraga, A., Jimeno, M.L., Gomez, M.D., Gomez-Gomez, L., 2012. Characterization of a glucosyltransferase enzyme involved in the formation of kaempferol and quercetin sophorosides in Crocus sativus. Plant Physiol. 159, 1335-1354.
  • Tung, N.H., Shoyama, Y., 2013. New minor glycoside components from saffron. J. Nat. Med. 67, 672-676.
  • U.S. Department of agriculture, agricultural research service (USDA), 2013. USDA National Nutrient Database for Standard Reference, Release 26. Nutrient Data Laboratory Home Page. http://www.ars.usda.gov/ba/bhnrc/ndl.
  • Vahedi, M., Govil, S., Kumar, Sh, Shrivastava, D., Karimi, R., Bisen, P.S., 2016. Therapeutic applications of Crocus sativus L. (saffron): a review. Nat. Prod. J. 6, 1-10.
  • Vignolini, P., Heimler, D., Pinelli, P., Ieri, F., Sciullo, A., Romani, A., 2008. Characterization of by-products of saffron (Crocus sativus L.) production. NPC Nat. Prod. Commun. 3 1959 - 1962.
  • Wang, P., Tong, Y., Tao, L., Shao, Y., Liu, X., 2014. Research progress on chemical constituents of Crocus sativus and their pharmacological activities. Chin. Tradit. Herb. Drugs 45, 3015-3029.
  • Wang, Y., Han, T., Zhu, Y., Zheng, C.J., Ming, Q.L., Rahman, K., Qin, L.P., 2010. Antidepressant properties of bioactive fractions from the extract of Crocus sativus L. J. Nat. Med. 64, 24-30.
  • Wu, Z., Robinson, D.S., Hughes, R.K., Casey, R., Hardy, D., West, S.I., 1999. Co-oxidation of β -carotene catalyzed by soybean and recombinant pea lipoxygenase. J. Agric. Food Chem. 47, 4899-4906.
  • Yayli, N., Kiran, Z., Seymen, H., Genc, H., 2001. Characterization of lipids and fatty acid methyl ester contents in leaves and roots of Crocus vallicola. Turk. J. Chem. 25, 391-395.
  • Yu-Zhu, Ting-Han, Hou, T.T., Hu, Y., Zhang, Q.Y., Rahman, K., Qin, L.P., 2008. Comparative study of composition of essential oil from stigmas and of extract from corms of Crocus sativus. Chem. Nat. Comp. 44, 666-667.
  • Zeka, K., Ruparelia, K.C., Sansone, C., Macchiarelli, G., Continenza, M.A., Arroo, R.R.J., 2018. New hydrogels enriched with antioxidants from saffron Crocus can find applications in wound treatment and/or beautification. Skin Pharmacol. Physiol. 31, 95-98.
  • Zhang, Z., Wang, C.Z., Wen, X.D., Shoyama, Y., Yuan, C.S., 2013. Role of saffron and its constituents on cancer chemoprevention. Pharm. Biol. 51, 920-924.
  • Zheng, C.J., Li, L., Ma, W.H., Han, T., Qin, L.P., 2011. Chemical constituents and bioactivities of the liposoluble fraction from different medicinal parts of Crocus sativus. Pharm. Biol. 49, 756-763.
  • Zhou, J., Xie, G., Yan, X., 2011. Encyclopedia of Traditional Chinese Medicines-Molecular, Structures, Pharmacological Activities, Natural Sources and Applications. Isolated Compounds A-C, vol. 1. Springer-Verlag, Berlin, pp. 3934 Heidelberg.