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Geranium psilostemon Ledeb. bitkisinden elde edilen fenolik bileşikler ve hidrolize olabilen tanenlerin sitotoksik ve genotoksik özelliklerinin değerlendirilmesi

Year 2017, Issue: 2, 63 - 72, 01.06.2017

Abstract

Geranium türleri, geleneksel tıpta tonik, diüretik, antidiyabetik, antidiyareal ve antihemoroidal olarak kullanılan tıbbi gıda bitkileridir. Geranium psilostemon Ledeb. Geraniaceae , fenolik bileşiklerce zengin, Türkiye’de yaygın olarak yetişen bir türdür. Bu çalışmanın amacı, G. psilostemon’dan elde edilen bileşiklerin sitotoksisitesinin ve genotoksisitesinin değerlendirilmesidir. Bileşiklerin sitotoksisitesi neutral red uptake NRU yöntemi ile belirlenmiştir. Genotoksik etkilerinin değerlendirilmesinde COMET kullanılmıştır. Bileşiklerin IC50 değerleri farklı hücre kültürlerinde sitotoksisitenin değerlendirilmesi için kullanılmıştır. 1,3,6-tri-O-galloil- β-glukopiranoz L1210 ve V79 hücrelerinde en çok sitotoksik etkiyi göstermiştir ve IC50 değerleri sırasıyla 3.7 ve 13 μg/ml’dır. Bunun yanısıra, HeLa hücrelerinde, 1,3,6-tri-O-galloil- β-glukopiranoz ve gallik acit en düşük IC50, sırasıyla 18 and 15 μg/ml değerine sahiptir. Tüm bileşikler kullanıldıkları bütün konsantrasyonlarda sitotoksik etki göstermiştir. Ayrıca, 50 μg/ml konsantrasyonda genotoksik etkileri de gösterilmiştir. G. psilestemon’dan izole edilen test bileşikleri, tıbbi gıda bitkileri olup sitotoksik ve genotoksik potansiyelleri bulunmaktadır. Dolayısıyla, bu biyolojik aktivitelerinin de değerlendirilmesi gerekir. Antikanser ve diğer biyolojik aktivitelerinin değerlendirilebilmesinde optimum konsntrasyonların belirlenmesi için ileri çalışmalara ihtiyaç vardır.

References

  • Davis PH. Geranium L. In: Davis PH. Editor. Flora of Turkey and East Aegean Islands Vol 2., Edinburg: Edinburgh University Press; 1966. pp. 441-474.
  • Aedo C, Garmendia FM, Pando F. World checklist of Geranium L. (Geraniaceae). An Jard Bot Madr 2013; 2: 211-52.
  • Baytop T. Therapy with Medicinal Plants in Turkey (Past and Present). Istanbul: Nobel Tip Kitabevleri; 1999.
  • Calzada F, Cervantes-Martinez JA, Yepez-Mulia L. In vitro antiprotozoal activity from the roots of Geranium mexicanum and its constituents on Entamoeba histolytica and Giardia lamblia. J Ethnopharmacol 2005; (1-2):191-193.
  • Wu N, Zu Y, Fu Y, Kong Y, Zhao J, Li X, Li J, Wink M, Efferth T. Activities and Xanthine Oxidase Inhibitory Effects of Extracts and Main Polyphenolic Compounds Obtained from Geranium sibiricum L. J Agric Food Chem 2010; 8:4737-4743.
  • Ertuğ F. An Ethnobotanical Study in central Anatolia (Turkey). Econ Bot 2000; 2:155-182.
  • Kargıoğlu M, Cenkci S, Serteser A, Konuk M, Vural G. Traditional Uses of Wild Plants in The Middle Aegean Region of Turkey. Human Ecol 2010; 3:429-450.
  • Şöhretoğlu D, Sakar MK, Sterner O. New galloylated flavonoid glycosides from Geranium stepporum Davis. Helv Chim Acta 2009; 520-524.
  • Elçim A, Behçet L. Geranium kalenderianum (Geraniaceae), a new species from Turkey. Ann Bot Fenn 2006; 451-455.
  • Karato M, Yamaguchi K, Takei S, Kino T, Yazawa K. Inhibitory effects of Pasuchaca (Geranium dielsiaum) extract on β-glucosidase in Mouse. Biosci Biotechnol Biochem 2006; 6: 1482-1484.
  • Toshkova R, Nikolova N, Ivanova E, Ivancheva S, Serkedjieva J. In vitro investigations on the effect of a plant preparation with antiviral activity on the functions of mice phagocyte cells. Pharmazie 2004; 150-154.
  • Şöhretoğlu D, Sakar MK, Ekizoğlu M, Özalp M. Free Radical Scavenging and Antimicrobial Activities of Three Geranium Species Growing in Turkey. FABAD 2007; 2:59-63.
  • Middleton E.Jr, Kandaswami C, Theoharides TC. The effects of plant flavonoids on mammalian cells: implications for inflammation, heart disease, and cancer. Pharmacol Rev 2000; 4: 673–751.
  • Velázquez-González C, Cariño-Cortés R, Gayosso de Lucio J, Ortiz MI, Arciniega M, Altamirano- Báez D, Jiménez-Ángeles L, Bautista-Ávila M. Antinociceptive and anti-inflammatory activities of Geranium bellum and its isolated compounds. BMC Complement Altern Med 2014; 506.
  • Şöhretoğlu D, Sabuncuoğlu SA, Sakar MK, Ozgüneş H, Sterner O. Antioxidant effects of secondary metabolites from Geranium psilostemon. Nat Prod Commun 2010; 6: 899-902.
  • Evans CA, Miller NJ. Antioxidant activities of flavonoids as bioactive components of food. Biochem Soc Trans 1996; 3: 790–795.
  • Sergediene E, Jonsson K, Szymusiak H, Tyrakowska B, Rietjens IM. Prooxidant toxicity of polyphenolic antioxidants to HL-60cells: description of quantitative structure-activity relationships. FEBS Lett 1999; 3: 392–396.
  • Selassie CD. Kapur S, Verma RP, Rosario M. Cellular apoptosis and cytotoxicity of phenolic compounds: A quantitative structure-activity relationship study. J Med Chem 2005; 23: 7234- 7242.
  • Jiang ZH, Wen XY, Tanaka T, Wu SY, Liu Z, Iwata H, Hirose Y, Wu S, Kouno S. Cytotoxic Hydrolysable Tannins from Balanophora japonica. J Nat Prod 2008; 4:719–723.
  • Sakagami H, Jiang Y, Kusama K, Ueha T, Toguchi M, Iwakura I, Satoh K, Ito H, Hatano T, Yoshida T. Cytotoxic activity of hydrolysable tannins against human oral tumor cell lines - A possible mechanism. Phytomedicine 2000; 1: 39-47.
  • Middleton E, Kandaswami C. The impact of plant flavonoids on mammalian biology: implications for immunity, inflammation and cancer. In: Harborne, J.B. editor The flavonoids: advances in research since 1986, London: Chapman & Hall; 1994. p. 619–652.
  • Fraga CG, Galleano M, Verstraeten SV, Oteiza PI. Basic biochemical mechanisms behind the health benefits of polyphenols. Mol Aspects Med 2010; 6:435–445.
  • Huang WY, Cai YZ, Zhang Y. Natural phenolic compounds from medicinal herbs and dietary plants: potential use for cancer prevention. Nutr Cancer 2010; 1: 1-20.
  • Evans WS. Pharmacognosy, 15th ed. China: Elsevier Limited;2002.
  • Papis E, Davies SJ, Jha AN. Relative sensitivity of fish and mammalian cells to the antibiotic, trimethoprim: cytotoxic and genotoxic responses as determined by neutral red retention, Comet and micronucleus assays. Ecotoxicology 2011; 1:208-217.
  • Vande Voorde J, Sabuncuoğlu S, Noppen S, Hofer A, Ranjbarian F, Fieuws S, Balzarini J, Liekens S. Nucleoside-catabolizing enzymes in mycoplasma-infected tumor cell cultures compromise the cytostatic activity of the anticancer drug gemcitabine. J Biol Chem. 2014; 289(19):13054-65.
  • Collins AR, Duthie SJ, Dobson VL. Direct enzymic detection of endogenous oxidative base damage in human lymphocyte DNA. Carcinogenesis 1993;9:1733-1735.
  • Singh NP, Danner DB, Tice RR, McCoy MT, Collins GD, Schneider EL. Abundant alkali-sensitive sites in DNA of human and mouse sperm. Exp Cell Res 1989; 2: 461-470.
  • Tournaire C, Croux S, Maurette MT, Beck I, Hocquaux M, Braun AM, Oliveros E J. Antioxidant activity of flavonoids: efficiency of singlet oxygen (1 delta g) quenching. Photochem Photobiol B 1993; 3: 205-15.
  • Venskutonis PR, Dedonyte V, Lazutka J, Slapsyte G, Maroziene A, Nemeikaite-Ceniene A, Cenas N, Miliauskas G. A preliminary assessment of singlet oxygen scavenging, cytotoxic and genotoxic properties of Geranium macrorrhizum extracts. Acta Biochim Pol 2010; 2: 157-163.
  • Galati G, O'Brien PJ. Potential toxicity of flavonoids and other dietary phenolics: significance for their chemopreventive and anticancer properties. Free Radic Biol Med 2004; 3:287-303.
  • Caltagirone S, Rossi C, Poggi A, Ranelletti FO, Natali PG, Brunetti M, Aiello FB, Piantelli M. Flavonoids apigenin and quercetin inhibit melanoma growth and metastatic potential. Int J Cancer 2000; 4: 595-600.
  • Yoshioka K, Kataoka T, Hayashi T, Hasegawa M, Ishi Y, Hibasami H. Induction of apoptosis by gallic acid in human stomach cancer KATO III and colon adenocarcinoma COLO 205 cell lines. Oncol Rep 2007; 6: 1221–1223.
  • Salucci M, Stivala LA, Maiani G, Bugianesi R, Vannini V. Flavonoids uptake and their effect on cell cycle of human colon adenocarcinoma cells (Caco2). Br J Cancer 2002; 86: 1645–1651.
  • Agarwal C, Tyagi A, Agarwal R. Gallic acid causes inactivating phosphorylation of cdc25A/ cdc25C-cdc2 via ATM-Chk2 activation, leading to cell cycle arrest, and induces apoptosis in human prostate carcinoma DU145 cells. Mol Cancer Ther 2006; 12: 3294-3302.
  • Faried A, Kurnia D, Faried LS, Usman N, Miyazaki T, Kato H, Kuwano H. Anticancer effects of gallic acid isolated from Indonesian herbal medicine, Phaleria macrocarpa (Scheff.) Boerl, on human cancer cell line. Int J Oncol 2007; 3: 605-613.
  • You BR, Park WH. Gallic acid-induced lung cancer cell death is related to glutathione depletion as well as reactive oxygen species increase. Toxicol In Vitro 2010; 5: 1356–1362.
  • You BR, Moon HJ, Han YH, Park WH. Gallic acid inhibits the growth of HeLa cervical cancer cells via apoptosis and/or necrosis Food Chem. Toxicol 2010; 5: 1334–1340.
  • Chandramohan Reddy T, Bharat Reddy D, Aparna A, Arunasree KM, Gupta G, Achari C, Reddy GV, Lakshmipathi V, Subramanyam A, Reddanna P. Anti-leukemic effects of gallic acid on human leukemia K562 cells: downregulation of COX-2, inhibition of BCR/ABL kinase and NF-κB inactivation. Toxicol in vitro 2012; 3:396-405.
  • Kamatham S, Kumar N, Gudipalli P. Isolation and characterization of gallic acid and methylgallate from the seed coats of Givotia rottleriformis Griff. and their anti-proliferative effect on human epidermoidcarcinoma A431 cells. Toxicol Report 2015 520–529.

Assesment of Cytotoxic and Genotoxic Properties of Phenolic Compounds and Hydrolysable Tannins from Geranium psilostemon Ledeb.

Year 2017, Issue: 2, 63 - 72, 01.06.2017

Abstract

Geranium species are medicinal food plants used as tonic, diuretic, antidiabetic, antidiarrheal, and antihemorrhoidal in traditional medicine. Geranium psilostemon Ledeb. Geraniaceae , which has a rich phenolic content, grows widely in Turkey. The aim of this study is to evaluate cytotoxicity and genotoxicity of the compounds isolated from G. psilostemon. Cytotoxic effects of the compounds were determined by neutral red uptake NRU assay. COMET assay was used for assesing genotoxic effects of the compounds. IC50 values of the compounds were calculated in different cell lines to evaluate cytotoxicity. 1,3,6-tri-O-galloyl-β-glucopyranose showed the most cytotoxic effect on L1210 and V79 cell lines and IC50 values of the compound were 3.7 and 13 μg/ml, respectively. Besides, in HeLa cell line, 1,3,6-tri-O-galloyl-β-glucopyranose and gallic acid had the lowest IC50, 18 and 15 μg/ml, respectively. All the compounds exhibited significant cytotoxic effects at all concentrations. Besides, they also showed genotoxic activity at 50 μg/ml. The tested compounds isolated from G. psilestemon, a medicinal food plant, have cytotoxic and genotoxic potential. Therefore, it should be considered regarding these biological acitivities. Further studies are necessary to determine the optimal concentrations of the compounds for evaluating their anticancer and other biological activities.

References

  • Davis PH. Geranium L. In: Davis PH. Editor. Flora of Turkey and East Aegean Islands Vol 2., Edinburg: Edinburgh University Press; 1966. pp. 441-474.
  • Aedo C, Garmendia FM, Pando F. World checklist of Geranium L. (Geraniaceae). An Jard Bot Madr 2013; 2: 211-52.
  • Baytop T. Therapy with Medicinal Plants in Turkey (Past and Present). Istanbul: Nobel Tip Kitabevleri; 1999.
  • Calzada F, Cervantes-Martinez JA, Yepez-Mulia L. In vitro antiprotozoal activity from the roots of Geranium mexicanum and its constituents on Entamoeba histolytica and Giardia lamblia. J Ethnopharmacol 2005; (1-2):191-193.
  • Wu N, Zu Y, Fu Y, Kong Y, Zhao J, Li X, Li J, Wink M, Efferth T. Activities and Xanthine Oxidase Inhibitory Effects of Extracts and Main Polyphenolic Compounds Obtained from Geranium sibiricum L. J Agric Food Chem 2010; 8:4737-4743.
  • Ertuğ F. An Ethnobotanical Study in central Anatolia (Turkey). Econ Bot 2000; 2:155-182.
  • Kargıoğlu M, Cenkci S, Serteser A, Konuk M, Vural G. Traditional Uses of Wild Plants in The Middle Aegean Region of Turkey. Human Ecol 2010; 3:429-450.
  • Şöhretoğlu D, Sakar MK, Sterner O. New galloylated flavonoid glycosides from Geranium stepporum Davis. Helv Chim Acta 2009; 520-524.
  • Elçim A, Behçet L. Geranium kalenderianum (Geraniaceae), a new species from Turkey. Ann Bot Fenn 2006; 451-455.
  • Karato M, Yamaguchi K, Takei S, Kino T, Yazawa K. Inhibitory effects of Pasuchaca (Geranium dielsiaum) extract on β-glucosidase in Mouse. Biosci Biotechnol Biochem 2006; 6: 1482-1484.
  • Toshkova R, Nikolova N, Ivanova E, Ivancheva S, Serkedjieva J. In vitro investigations on the effect of a plant preparation with antiviral activity on the functions of mice phagocyte cells. Pharmazie 2004; 150-154.
  • Şöhretoğlu D, Sakar MK, Ekizoğlu M, Özalp M. Free Radical Scavenging and Antimicrobial Activities of Three Geranium Species Growing in Turkey. FABAD 2007; 2:59-63.
  • Middleton E.Jr, Kandaswami C, Theoharides TC. The effects of plant flavonoids on mammalian cells: implications for inflammation, heart disease, and cancer. Pharmacol Rev 2000; 4: 673–751.
  • Velázquez-González C, Cariño-Cortés R, Gayosso de Lucio J, Ortiz MI, Arciniega M, Altamirano- Báez D, Jiménez-Ángeles L, Bautista-Ávila M. Antinociceptive and anti-inflammatory activities of Geranium bellum and its isolated compounds. BMC Complement Altern Med 2014; 506.
  • Şöhretoğlu D, Sabuncuoğlu SA, Sakar MK, Ozgüneş H, Sterner O. Antioxidant effects of secondary metabolites from Geranium psilostemon. Nat Prod Commun 2010; 6: 899-902.
  • Evans CA, Miller NJ. Antioxidant activities of flavonoids as bioactive components of food. Biochem Soc Trans 1996; 3: 790–795.
  • Sergediene E, Jonsson K, Szymusiak H, Tyrakowska B, Rietjens IM. Prooxidant toxicity of polyphenolic antioxidants to HL-60cells: description of quantitative structure-activity relationships. FEBS Lett 1999; 3: 392–396.
  • Selassie CD. Kapur S, Verma RP, Rosario M. Cellular apoptosis and cytotoxicity of phenolic compounds: A quantitative structure-activity relationship study. J Med Chem 2005; 23: 7234- 7242.
  • Jiang ZH, Wen XY, Tanaka T, Wu SY, Liu Z, Iwata H, Hirose Y, Wu S, Kouno S. Cytotoxic Hydrolysable Tannins from Balanophora japonica. J Nat Prod 2008; 4:719–723.
  • Sakagami H, Jiang Y, Kusama K, Ueha T, Toguchi M, Iwakura I, Satoh K, Ito H, Hatano T, Yoshida T. Cytotoxic activity of hydrolysable tannins against human oral tumor cell lines - A possible mechanism. Phytomedicine 2000; 1: 39-47.
  • Middleton E, Kandaswami C. The impact of plant flavonoids on mammalian biology: implications for immunity, inflammation and cancer. In: Harborne, J.B. editor The flavonoids: advances in research since 1986, London: Chapman & Hall; 1994. p. 619–652.
  • Fraga CG, Galleano M, Verstraeten SV, Oteiza PI. Basic biochemical mechanisms behind the health benefits of polyphenols. Mol Aspects Med 2010; 6:435–445.
  • Huang WY, Cai YZ, Zhang Y. Natural phenolic compounds from medicinal herbs and dietary plants: potential use for cancer prevention. Nutr Cancer 2010; 1: 1-20.
  • Evans WS. Pharmacognosy, 15th ed. China: Elsevier Limited;2002.
  • Papis E, Davies SJ, Jha AN. Relative sensitivity of fish and mammalian cells to the antibiotic, trimethoprim: cytotoxic and genotoxic responses as determined by neutral red retention, Comet and micronucleus assays. Ecotoxicology 2011; 1:208-217.
  • Vande Voorde J, Sabuncuoğlu S, Noppen S, Hofer A, Ranjbarian F, Fieuws S, Balzarini J, Liekens S. Nucleoside-catabolizing enzymes in mycoplasma-infected tumor cell cultures compromise the cytostatic activity of the anticancer drug gemcitabine. J Biol Chem. 2014; 289(19):13054-65.
  • Collins AR, Duthie SJ, Dobson VL. Direct enzymic detection of endogenous oxidative base damage in human lymphocyte DNA. Carcinogenesis 1993;9:1733-1735.
  • Singh NP, Danner DB, Tice RR, McCoy MT, Collins GD, Schneider EL. Abundant alkali-sensitive sites in DNA of human and mouse sperm. Exp Cell Res 1989; 2: 461-470.
  • Tournaire C, Croux S, Maurette MT, Beck I, Hocquaux M, Braun AM, Oliveros E J. Antioxidant activity of flavonoids: efficiency of singlet oxygen (1 delta g) quenching. Photochem Photobiol B 1993; 3: 205-15.
  • Venskutonis PR, Dedonyte V, Lazutka J, Slapsyte G, Maroziene A, Nemeikaite-Ceniene A, Cenas N, Miliauskas G. A preliminary assessment of singlet oxygen scavenging, cytotoxic and genotoxic properties of Geranium macrorrhizum extracts. Acta Biochim Pol 2010; 2: 157-163.
  • Galati G, O'Brien PJ. Potential toxicity of flavonoids and other dietary phenolics: significance for their chemopreventive and anticancer properties. Free Radic Biol Med 2004; 3:287-303.
  • Caltagirone S, Rossi C, Poggi A, Ranelletti FO, Natali PG, Brunetti M, Aiello FB, Piantelli M. Flavonoids apigenin and quercetin inhibit melanoma growth and metastatic potential. Int J Cancer 2000; 4: 595-600.
  • Yoshioka K, Kataoka T, Hayashi T, Hasegawa M, Ishi Y, Hibasami H. Induction of apoptosis by gallic acid in human stomach cancer KATO III and colon adenocarcinoma COLO 205 cell lines. Oncol Rep 2007; 6: 1221–1223.
  • Salucci M, Stivala LA, Maiani G, Bugianesi R, Vannini V. Flavonoids uptake and their effect on cell cycle of human colon adenocarcinoma cells (Caco2). Br J Cancer 2002; 86: 1645–1651.
  • Agarwal C, Tyagi A, Agarwal R. Gallic acid causes inactivating phosphorylation of cdc25A/ cdc25C-cdc2 via ATM-Chk2 activation, leading to cell cycle arrest, and induces apoptosis in human prostate carcinoma DU145 cells. Mol Cancer Ther 2006; 12: 3294-3302.
  • Faried A, Kurnia D, Faried LS, Usman N, Miyazaki T, Kato H, Kuwano H. Anticancer effects of gallic acid isolated from Indonesian herbal medicine, Phaleria macrocarpa (Scheff.) Boerl, on human cancer cell line. Int J Oncol 2007; 3: 605-613.
  • You BR, Park WH. Gallic acid-induced lung cancer cell death is related to glutathione depletion as well as reactive oxygen species increase. Toxicol In Vitro 2010; 5: 1356–1362.
  • You BR, Moon HJ, Han YH, Park WH. Gallic acid inhibits the growth of HeLa cervical cancer cells via apoptosis and/or necrosis Food Chem. Toxicol 2010; 5: 1334–1340.
  • Chandramohan Reddy T, Bharat Reddy D, Aparna A, Arunasree KM, Gupta G, Achari C, Reddy GV, Lakshmipathi V, Subramanyam A, Reddanna P. Anti-leukemic effects of gallic acid on human leukemia K562 cells: downregulation of COX-2, inhibition of BCR/ABL kinase and NF-κB inactivation. Toxicol in vitro 2012; 3:396-405.
  • Kamatham S, Kumar N, Gudipalli P. Isolation and characterization of gallic acid and methylgallate from the seed coats of Givotia rottleriformis Griff. and their anti-proliferative effect on human epidermoidcarcinoma A431 cells. Toxicol Report 2015 520–529.
There are 40 citations in total.

Details

Primary Language English
Journal Section Research Article
Authors

Suna Sabuncuoğlu

Solmaz Mohammadi Nejad This is me

Didem Şöhretoğlu This is me

Publication Date June 1, 2017
Published in Issue Year 2017 Issue: 2

Cite

Vancouver Sabuncuoğlu S, Nejad SM, Şöhretoğlu D. Assesment of Cytotoxic and Genotoxic Properties of Phenolic Compounds and Hydrolysable Tannins from Geranium psilostemon Ledeb. HUJPHARM. 2017(2):63-72.