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Anticancer Properties of Viburnum 47 Anticancer properties of Viburnum 47 © Wydawnictwo UR 2018 http://www.ejcem.ur.edu.pl/en/ ISSN 2544-1361 (online); ISSN 2544-2406 European Journal of Clinical and Experimental Medicine doi: 10.15584/ejcem.2018.1.8 Eur J Clin Exp Med 2018; 16 (1): 47–52 REVIEW PAPER Agnieszka Stępień 1(ABDGF), David Aebisher 2(BDGF), Dorota Bartusik-Aebisher 3(BDGF) Anticancer properties of Viburnum 1 Centre for Innovative Research in Medical and Natural Sciences, Medical Faculty, University of Rzeszow, Poland 2 Department of Human Immunology, Faculty of Medicine, University of Rzeszow, Poland 3 Department of Experimental and Clinical Pharmacology, Faculty of Medicine, University of Rzeszow, Poland ABSTRACT Aim. The aim of this paper is to provide an overview of the anticancer properties of different species of Viburnum. Materials and methods. Forty nine papers that discuss the medicinal history and current research of Viburnum species as phy- totherapeutic agent were used for this discussion. Literature analysis. The results of scientific research conducted in vitro indicate that the compounds present in the extracts of Viburnum significantly affect the development of cancer cells such as leukemia, cervical cancer, breast, colon, lung, skin and stomach. This indicates that they may be used as a therapeutic agent to support oncological therapies. Keywords. antitumor activity, Viburnum species, cytotoxic activity Introduction Viburnum (Viburnum L.) is a shrub currently belong- ing to the family Adoxaceae previously Viburnaceae or Caprifoliaceae and within the genus represents over 250 species around the world.1 It is a species widely dis- tributed in the temperate zone in central and south- ern Europe and North America and in the mountains of northern Africa and south-east Asia.2-4 In Poland, the wild species found are viburnum coral (Viburnum opulus) (Figure 1 and 2) and viburnum hordowina (V. 5 lantana). It is a shrub blooming white (Figure 3) – mar- ginal and middle pink-white flowers. Figure 1. Fruit of viburnum coral (Viburnum opulus) (photo by Małgorzata Szczygieł) Corresponding author: Agnieszka Stępień, e-mail: [email protected] Participation of co-authors: A – Author of the concept and objectives of paper; B – collection of data; C – implementation of re- search; D – elaborate, analysis and interpretation of data; E – statistical analysis; F – preparation of a manuscript; G – working out the literature; H – obtaining funds Received: 15.12.2018 | Accepted: 18.02.2018 Publication date: March 2018 Stępień A, Aebisher D, Bartusik-Aebisher D. Anticancer properties of Viburnum. Eur J Clin Exp Med. 2018;16(1):47–52. doi: 10.15584/ejcem.2018.1.8 48 European Journal of Clinical and Experimental Medicine 2018; 16 (1): 47–52 on the analysis of the obtained incubation results with these cell lines, they determined that the extract (organ- ic solvents) and selected fractions inhibited cell prolif- eration. Further researchers also undertook the analysis of Bibi et al. to assess Viburnum foetens cytotoxicity against breast cancer cell lines (MCF-7).38 The phyto- chemical analysis of the crude extract from the leaves of Viburnum foetens showed the presence of anthraqui- nones, saponins, tannins, flavonoids and coumarins. On the other hand, the methanol fraction of the extract, less expensive than anthraquinones and saponins, was char- acterized by the highest high anti-cancer activity. Figure 2. Shrub of viburnum coral with ripe fruits (photo The above results suggested to researchers the need by Małgorzata Szczygieł) to undertake further more precise phytochemical ana- lyzes of the obtained extracts and fractions from Vibur- num in order to isolate and define specific compounds responsible for cytotoxic and anticancer properties. This was accomplished by Fukuyma et al. by deter- mining that the extract obtained from the species Vi- burnum luzonicum is a source of iridoid glycosides and aglycones (Table 1, item 1). Analysis of the results of incubation of these compounds obtained from the V. luzonicum extract with the same human epithelial tu- mor cell line (HeLa S3) allowed for an assessment of their cytotoxicity. It was demonstrated that glycosides 1 and 2 and agglutinates 5-9 showed moderate cyto- toxicity against this line, while 3 and 4 showed no cy- totoxic activity. Researchers continued research on the isolation Figure 3. Shrub of viburnum coral with flowers (photo by of further compounds from the extract from the dried Amelia Prus) leaves of Viburnum luzonicum. Spectroscopic methods confirmed the chemical structure of four iridoid alde- Many species of Viburnum are widely known and hydes bearing (E) – or (Z) – p-coumaroyl group (1-4) have been used for many years in folk medicine due to (Table 1 item 2). The cytotoxicity test of these com- its valuable properties. They are also characterized by pounds also against the same HeLa S3 tumor cell line antibacterial, anti-inflammatory, sedative, hepatopro- indicated that compounds 1-3 exhibited moderate cy- tective, antinociceptive and anti-asthmatic properties.6-9 totoxicity.40 Numerous biologically active compounds are respon- In his research, Cheng et al. (2011)41 isolated from sible for these properties which originate from various an extract of Viburnum chingii leaves, oleanane triter- species of Viburnum.10-16 The scientific literature pres- penoids (1-2) and vibesan diterpenoid (3) together with ents the results of phytochemical studies confirming the 7 other compounds (4-10) (Table 1, item 3). They then presence of triterpenoid compounds 17-22, iodoids, 23-25 examined the cytotoxicity of these compounds to hu- diterpenoid/diterpenes 26,7, vibroids, lignans 31-34, flavo- man cell lines myeloid leukemia (HL-60), hepatocellular noids 35-36, polyphenols 18-27, and vitamins in fruit, leaves, carcinoma (SMMC-7721), alveolar basal epithelial cells twigs of various species of Viburnum (table 1). These (A-549), breast (SK-BR-3) and epithelioid carcinoma compounds are an important group among compounds (PANC- 1). The highest cytotoxicity for all cell lines was derived from natural products in the prevention and demonstrated by compound 3 and the lowest compounds treatment of tumors. Our review presents the character- 2, 4, 5, 9 and 10 with the exception of compound 4 show- istics of cytotoxic and antineoplastic extracts and com- ing no cytotoxicity to the SMMC-7721 cell line. pounds isolated from various species of Viburnum. Li et al. (2015)determined that the branches and Waheed et al. (2013) in their study analyzed the ob- leaves of Viburnum odoratissimum var. odoratissimum tained extract and fractions from the leaves of Vibur- contain diterpenoids and six known compounds with num foetens L. for interaction with human breast tumor confirmed structure (Table 1, item 4).42 Subsequently, cell lines (MDA-MB-468) and colon (Caco-2).37 Based they investigated the cytotoxicity assessment of newly Anticancer properties of Viburnum 49 Table 1. Compounds isolated from various species Viburnum Compounds Method analysis -techniques References 1. Viburnum I. iridoids glucosides: Nuclear Magnetic Resonance Fukuyama et al. 1. luzonoside A , (NMR 1H and 13C); (2004)39 2. luzonoside B, Infrared Spectroscopy (IR); 3. luzonoside C, High Resolution Electrospray 4. luzonoside D, Ionization Mass Spectrometry iridoid aglycons bearing (E)- or (Z)-p-coumaroyl groups: (HR-ESI MS). 5. luzonoid A, 6. luzonoid B, 7. luzonoid C, 8. luzonoid D, 9. luzonoid E, 10. luzonoid F, 11. luzonoid G 2. Viburnum luzonicum II. aldehydes: Nuclear Magnetic Resonance Fukuyama et al. 1. luzonials A, (NMR 1H and 13C); (2005)40 2. luzonials B, Infrared Spectroscopy (IR); 3. luzonidials A, High Resolution Electrospray 4. luzonidials B Ionization Mass Spectrometry (HR-ESI MS). 3. Viburnum chingii III. oleanane triterpenoids: Nuclear Magnetic Resonance Chen et 1.1α,3β- dihydroxy-11α-methoxy-olean-12-ene, (NMR 1H and 13C); al.(2011)41 2.1α,2β--dihydroxy-olean-9(11),12-diene, Infrared Spectroscopy (IR); 3. vibsane-type diterpenoid: High Resolution Electrospray IV. vibsaol B, Ionization Mass Spectrometry 5. 2α,3β-dihydroxy-20(29)-lupene, (HR-ESI MS). 6. 6α-hydroxy-3-on-20(29)-lupen-28-oic acid, 7.3,6-dion-20(29)- lupen-28-oic acid, 8. hederagenin acid, 9. castanopsone, 10. 3α,6β -dihydroxy-20(29)-lupene Viburnum odoratissimum var. odoratissimum IV. diterpenoids: Nuclear Magnetic Resonance Li et al. (2015)42 1. dehydrovibsanin G, (NMR 1H and 13C); 2. (+) - 9’-0-senecioyllariciresinol, Infrared Spectroscopy (IR); 3. vibsanin C, High Resolution Electrospray 4. vibsanin H, Ionization Mass Spectrometry 5. (8 Z) -10-epivibsanin C, (HR-ESI MS). 6. (+)-9’-0-isovaleryllariciresinol , 7. 9-aldehynevibsanol, 8. vibsanol Viburnum odoratissimum V. vibsane-type diterpenoids: Nuclear Magnetic Resonance Yu et al. (2016) 43 (NMR 1H and 13C); 1. vibsanin A, High Resolution Electrospray Ionization Mass Spectrometry (HR-ESI MS). Viburnum odoratissimum VI. diterpenoids: Nuclear Magnetic Resonance He et al. (2016) 44 1.vibsanol C, (NMR 1H and 13C); 2. vibsanol D, Infrared (IR); 3. vibsanol E, Electron Impact Mass Spectrom- 4. vibsanol F, etry (EIMS); 5.Vibsanol G, High Resolution Electrospray 6. vibsanol H, Ionization Mass Spectrometry 7. vibsanin X. (HR-ESI MS). 50 European Journal of Clinical and Experimental Medicine 2018; 16 (1): 47–52 Viburnum mongolicium VII. nor-dammarane triterpenoids: Wang et al. (2013) 1. 3β,12β-dihydroxy-25,26,27-trinordammara-22-en -24,20-olide , Nuclear Magnetic Resonance 45 2. 3β,12β-dihydroxy-24α-methoxy-25,26,27-trinordammara-20,24- (NMR 1H and 13C); epoxy, Infrared (IR); 3. 3β-0-acetyl-12β-hydroxy-23,24,25,26,27-hexanordammarane-20- Electron Impact Mass Spectrom- one etry (EIMS); 4.12β-0-acetyl-15α-hydroxy-17β-methoxy-3-oxo-20,21,22- High Resolution Electrospray 23,24,25,26,27-octanordammanrane, Ionization Mass Spectrometry 5. 12β-0-acetyl-15α,17β-dihydroxy-3-oxo-20,21,22-23,24,25,26,27 (HR-ESI MS). -octanordammanrane, 6.12β,15α-dihydroxy-3-oxo-17-en-20,21,22-23,24,25,26,27-octanor- dammanrane , 7.12β-hydroxy-3-oxo-24α-methoxy- 25,26,27- trinordam- mara-20,24-epoxy, 8.
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