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Home , Cyclamen, Cyclamen alpinum, Cyclamen mirabile, Cyclamen parviflorum, Cyclamen repandum

International Journal of Advances in Science Engineering and Technology, ISSN: 2321-9009 Volume-5, Issue-3, Jul.-2017 http://iraj.in MEDICINAL PROPERTIES AND BIOLOGICAL ACTIVITIES OF ALPINUM ()

1SEVKI ARSLAN, 2MEHMET CICEK

1,2Department of Biology, Faculty of Science and Arts, University of Pamukkale 20070 Denizli, Turkey E-mail: [email protected], [email protected]

Abstract- In this paper, the biological activity studies on and its medicinal properties (anti-inflammatory, antinociceptive, antioxidant, antimicrobial, antifungal, antiseptic, insecticidal, cytotoxic and enzyme activity) is reviewed. Due to the saponins they carry, the Cyclamen have important and diverse biological activities (diuretic, purgative, antirheumatic, antifungal, antimicrobial, insecticide, antioxidant, cytotoxic and antitumoral etc.).

Keywords: Biological Activity, Cyclamen alpinum, Medicinal , Turkey.

I. INTRODUCTION mentioned that C. alpinum (as C. trochopteranthum) is close to C. coum. Cyclamen alpinum is a perennial Humans have been using for various purposes with tuberous plant. Its are oval to round, since ancient times. These uses are mostly in the form upper surface green and red-purple below. of nutrition and treatment. In addition to these, spice, have 5 . Corolla lobes are patent, broadly ovate, perfumery, dentistry, industrial and medical uses are nearly to 13 x 10 mm, with acute or subacute apex, also very common. Herbal drugs are used as direct or pale rose-pink or bright pink or magenta color. Its herbal mixtures. According to World Health fruiting pedicels are coiled from apex. Organization (WHO) records, the majority of the world's population reported using "traditional III. ETHNOBOTANY medicine" for treatment. Treating diseases using medical plants is still keeping up to date. These There are many data on the use of Cyclamen taxa in practices, which are made under the name of traditional folk medicine. There is also information “alternative medicine”, traditional medicine or on the use of these species both internally and “complementary medicine”, also play an important externally. Cyclamen is a plant of medical value, role in world trade [1]. besides having an important place in ornamental Anatolia is one of the important values in terms of plants. Many Cyclamen species are known to be used plant diversity and ethnobotanical culture. Turkish in hemorrhoids, eczema, and wound healing. It has flora contains 1.251 genera and about 12,000 taxa also been reported to be used against infertility. There (with and varieties) belonging to 174 are also knowledge that its have been the usage families, and it is the gene center for many plants [2]. as sedative, anthelmintic and laxative [4].

The Cyclamen is one of the perennial bulbous IV. BIOLOGICAL ACTIVITY or tuberous plant species of the Primulaceae. It contains 30 taxa belonging to 20 species found in the Cyclamen species contain saponin, anthocyanin, Mediterranean Region, Southern , West Asia terpene and glycoside. There are a lot of studies and North Africa. The genus Cyclamen is represented carried out with extracts obtained from their tubers on by 11 species and 3 subspecies, in a total 12 taxa, in cytotoxic, antimicrobial, spermicidal, analgesic, and Turkey. 6 species of them are endemic. They bloom anti-inflammatory activities of [5, 6, 7, 8]. usually in February-April. The Cyclamen name is Cyclamen alpinum is one of the endemic species of derived from the word “cyclos” meaning circle in cyclamens in Turkey. It is a species that grows , because of be round its under-soil tubers. naturally in the south-western part of Turkey, Cyclamen species is a favorite plant as ornamental especially in Antalya, Muğla and Denizli. Many plant, because of enormous beauty of its leaves and cyclamen species are widely used as an ethno- flowers. medicine for treatment of hemorrhoids, eczema and Cyclamen alpinum is an endemic species to Turkey. expelling digestive tract worms. It grows in stony ground under bushes, forests and on serpentine and limestone in west Phytochemical studies about Cyclamen alpinum have Anatolia. been very limited. Two new triterpene saponins and three saponins namely, deglucocyclamin I, cyclamin II. MORPHOLOGY and mirabilin were isolated from the tubers of Cyclamen alpinum [9]. Moreover, gallic acid, 3,4- Cyclamen alpinum was described by Schwarz in 1975 dihydroxy benzoic acid, 4-dihydroxy benzoic acid, as C. trochopteranthum. In Flora of Turkey [3], it is chlorogenic acid, vanilic acid, cafeic acid, p-coumaric

Medicinal Properties and Biological Activities of Cyclamen Alpinum (Primulaceae)

67 International Journal of Advances in Science Engineering and Technology, ISSN: 2321-9009 Volume-5, Issue-3, Jul.-2017 http://iraj.in acid, cinnamic acid, ferulic acid was quantitatively activities of this plant due to limited studies about C. determined ethanol extract of Cyclamen alpinum’s alpinum. We believe that further biological studies on tubers [10]. the species will contribute to use of the plant in drug industry in the future. Similar to phytochemical studies about Cyclamen alpinum, biological activity studies are also limited. REFERENCES Our group demonstrated the drug interaction and cytotoxic properties of ethanol extract of Cyclamen [1] T. Ersöz, “Bitkisel ilaçlar ve gıda takviyeleri ile ilgili genel yaklaşım ve sorunlar”, MİSED, Number: 27-28, pp. 1-212, alpinum’s tubers [11, 12]. Cytochrome P450 2012. dependent drug metabolizing enzyme activities, and [2] G. Kendir and A. Güvenç, “Etnobotanik ve Türkiye’de their protein and mRNA levels were significantly yapılmış etnobotanik çalışmalara genel bir bakış”, changed as a result of cyclamen treatment. These Hacettepe Ü., Eczacılık Fak. Dergisi, vol.30(3), pp. 49-80, 2010. results may cause not only inhibition and/or induction [3] P.H. Davis (ed.) Flora of Turkey and the East Aegean of the metabolism of co-administered drugs but also Islands vols. 1-9. Edinburgh University Press, Edinburgh, development of toxicity and carcinogenesis due to 1965-1985. induction of these enzymes [11]. Moreover, cyclamen [4] E. Speroni, R. Cervellati, S. Costa, S. Dall’Acqua, M.C. Guerra, C. Panizzolo, A. Utan, and G. Innocenti, treatment revealed a concentration-dependent “Analgesic and antiinflammatory activity of Cyclamen cytotoxic effect on HEPG2 and Caco2cell lines in a repandum” S. et S. Phytother. Res., vol.21, pp. 684–689, dose-dependent manner. It was found that LC50 2007. value of the cyclamen extract was 50 µg/mL and 125 [5] İ. Çalış, M. Ersan, S. Şatana, A. Yürüker, P. Kelican, R. Demirdamar, R. Alacam N. Tanker, H. Ruegger and O. µg/mL in HepG2 and Caco-2 cell lines, respectively Sticherr, “Triterpene saponins from [12]. Another study showed that saponins isolated and their biological activities”, J. Nat. Prod., vol.60, pp. from tubers of Cyclamen alpinum showed weak 315-318, 1997. cytotoxic activity when tested against HT-29 and [6] S. Dall’Acqua, I. Castagliuolo, P. Brun, F. Ditadi, G. Palù and G. Innocenti, “Triterpene glycosides with in vitro anti- HCT 116 tumor colon cancer cells [10]. All of these inflammatory activity from tubers”, results showed that cytotoxic activity may be due to Carbohydrate Research, vol.345, pp. 709–714, 2010. the presence of phenolics and saponins present in the [7] A.M. Mahasneh and A.A. El-Oqlah, “Antimicrobial tubers of cyclamen. Cytotoxic activity of the ethanol activity of extracts of herbal plants used in the traditional medicine of Jordan”, J. Ethnopharmacol, vol.64, pp. 271- extracts of tubers and leaves of C. alpinum were 276, 1999. determined by using brine shrimp (Artemia salina L.) [8] M. Primorac, D. Sekulovic and S. Antonic, “In vitro lethality test and the LC50 value was determined. determination of the spermicidal activity of plant Although extract showed moderate cytotoxic saponins”, Pharmazie, vol.40(8), p. 585, 1985. [9] G. Mihci-Gaidi, S. Özbey, I. Orhan, B. Şener, T. activity against brine shrimp (LD50= 122.56 µg/mL), Miyamoto, J.F. Mirjolet, O. Duchamp, A.C. Mitaine-Offer extract had higher cytotoxicty (LD50= 9.89 and M.A. Lacaille-Dubois, “Triterpene saponins from µg/mL) [13]. Larvicidal activity of the tuber extracts Cyclamen trocopteranthum”, Planta Medica, vol.76(8), pp. of Cyclamen alpinum against Culex pipiens L. 818-821, 2010. [10] M. Turan, “Cyclamen alpinum ve (Diptera: Culicidae) was also determined. It was ekstraktlarinin fenolik bileşenleri ve bazi biyolojik determined that the young larval stages were more özelliklerinin belirlenmesi”, Ms. Thesis, 2016. susceptible to extract when compared to the older [11] Ş. Arslan, Ö. Özgün, G. Çelik, A. Semiz, O. Düşen, R. stages. The lowest concentration of C. alpinum Mammadov and A. Şen, "Effects of Cyclamen trochopteranthum on hepatic drug-metabolizing enzymes", extract (100 ppm) only achieved 16.6% mortality of Arch. Biol. Sci., Belgrade, 63 (3), 545-555, 2011. Culex pipiens L at 72 h post exposure but at 96 h [12] Ş. Arslan and Ö. Özgün, “Cyclamen trochopteranthum: mortality significantly increased to 40.0% [14]. Also, Cytotoxic activity and possible adverse interactions antioxidant activity of ethanol, methanol and acetone including drugs and carcinogens”, Chin J Integr Med. doi:10.1007/s11655-012-1253-1, 2012. extract of C. alpinum was determined by DPPH, [13] S. Düşen, Ç. Aydın, H. Yaka Gül, C. Özay, O. Düşen and FRAP, ABTS, β-carotene-linoleic acid. All of these R. Mammadov, “In vitro cytotoxic activities of Cyclamen extract showed moderately high antioxidant activity L. (Primulaceae) ethanol extracts from Turkey”, Fresenius [10]. Environmental Bulletin, vol.25(12a), pp. 6224-6228, 2016. [14] E. Öz, S. Koç, O. Düşen, R. Mammadov and H. Çetin, “Larvicidal activity of Cyclamen (Myrsinaceae) extracts CONCLUSIONS against the larvae of West Nile virus vector Culex pipiens L. (Diptera: Culicidae)”, Asian Pacific Journal of Tropical In conclusion, more phytochemical and biologic Medicine, vol.6(6), pp. 449-452, 2013. activity studies should be done to isolate and identify the active components responsible for biological

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Medicinal Properties and Biological Activities of Cyclamen Alpinum (Primulaceae)

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