Measurement of anticancer, antidiabetic and anticholinergic properties of sumac (Rhus coriaria): analysis of its phenolic compounds by LC–MS/MS

  • Hatice Tohma
  • Ahmet Altay
  • Ekrem KöksalEmail author
  • Ahmet Ceyhan Gören
  • İlhami Gülçin
Original Paper


The present study aimed to investigate Sumac (Rhus coriaria) for anticancer, antidiabetic, anticholinergic activities and total phenolic and flavonoid contents. Two solvents, water and ethanol, were used for extraction. For anticancer activity, the extracts were tested against human cancer cell lines including HT-29 and MCF-7. The cell growth inhibition rate was measured via XTT assay. The antidiabetic activity of the sumac extracts was measured by the inhibition of α-glycosidase and α-amylase enzymes, whereas the anticholinergic activity was measured via the inhibition of acetylcholinesterase and butyrylcholinesterase enzymes. The total phenolic and flavonoid contents were determined using the Folin–Ciocalteau and the aluminum chloride colorimetric methods, respectively. Liquid chromatography–mass spectrometry/mass spectrometry (LC–MS/MS) method was used for the separation, identification and quantification of phenolic compounds in the samples. The ethanolic extract had higher phenolic and phenolic contents than aqueous extract. It exhibited substantial antiproliferative, antidiabetic and anticholinergic activities. The aqueous extract of sumac showed moderate therapeutic efficiency in all the preformed assays. LC–MS/MS study revealed fumaric acid as a main compound in both the ethanolic (452.78 mg/kg) and aqueous (180.72 mg/kg) extracts. These results suggest that sumac may have health-enhancing effects and act as inhibitors of certain enzymes or interfering with some cellular pathways.


Sumac Rhus coriaria Anticancer activity Anticholinergic activity α-Glycosidase α-Amylase 


Compliance with ethical standards

Conflict of interest

The authors declare that there are no conflicts of interest.


  1. 1.
    A.H. Mokdad, E.S. Ford, B.A. Bowman, W.H. Dietz, F. Vinicor, V.S. Bales, J.S. Marks. Prevalence of obesity, diabetes, and obesity-related health risk factors. JAMA 289, 76–79 (2003) (2001)Google Scholar
  2. 2.
    C.J. Murray, A.D. Lopez, Measuring the global burden of disease. New Engl. J. Med. 369, 448–457 (2013)Google Scholar
  3. 3.
    H. Adlercreutz, Western diet and western diseases: some hormonal and biochemical mechanisms and associations. Scand. J. Clin. Lab. Invest. Suppl. 50(s201), 3–23 (1990)Google Scholar
  4. 4.
    K.S. Petersen, M.R. Flock, C.K. Richter, R. Mukherjea, J.L. Slavin, P.M. Kris-Etherton, Healthy dietary patterns for preventing cardiometabolic disease: the role of plant-based foods and animal products. Curr. Dev. Nutr. 1(12), 117.001289 (2017)Google Scholar
  5. 5.
    A.N. Li, S. Li, Y.J. Zhang, X.R. Xu, Y.M. Chen, H.B. Li, Resources and biological activities of natural polyphenols. Nutrients 6, 6020–6047 (2014)Google Scholar
  6. 6.
    İ. Gülçin, Antioxidant activity of caffeic acid (3,4-dihydroxycinnamic acid). Toxicology, 217, 213–220 (2006)Google Scholar
  7. 7.
    İ. Gülçin, Antioxidant and antiradical activities of l-carnitine. Life Sci. 78, 803–811 (2006)Google Scholar
  8. 8.
    A. Zalacain, M. Prodanov, M. Carmona, G.L. Alonso, Optimisation of extraction and identification of gallotannins from sumac leaves. Biosyst. Eng. 84(2), 211–216 (2003)Google Scholar
  9. 9.
    F. Candan, Effect of Rhus coriaria L. (Anacardiaceae) on superoxide radical scavenging and xanthine oxidase activity. J. Enzyme Inhib. Med. Chem. 18, 59–62 (2003)Google Scholar
  10. 10.
    E. Bursal, E. Köksal, Evaluation of reducing power and radical scavenging activities of water and ethanol extracts from sumac (Rhus coriaria L.). Food Res. Int. 44, 2217–2221 (2011)Google Scholar
  11. 11.
    M. Ozcan, H. Haciseferoğullari, A condiment sumac (Rhus coriaria L.) fruits: some physicochemical properties. Bulg. J. Plant Physiol 30, 74–84 (2004)Google Scholar
  12. 12.
    I.M. Abu-Reidah, M.S. Ali-Shtayeh, R. Jamous, D. Arráez-Román, A. Segura-Carretero, HPLC-DAD-ESI-MS/MS screening of bioactive components from Rhus coriaria L. (Sumac) fruits. Food Chem 166, 179–191 (2015)Google Scholar
  13. 13.
    P.Y. Aw-Yong, P.H. Gan, A.O. Sasmita, S.T. Mak, A.P.K. Ling Nanoparticles as carriers of phytochemicals: recent applications against lung cancer. Int. J. Res. Biomed. Biotechnol. 7, 1–11 (2018)Google Scholar
  14. 14.
    Y.Z. Cai, Q. Luo, M. Sun, H. Corke, Antioxidant activity and phenolic compounds of 112 traditional Chinese medicinal plants associated with anticancer. Life Sci. 74, 2157–2184 (2004)Google Scholar
  15. 15.
    C.S. Charron, H.D. Dawson, J.A. Novotny, Garlic influences gene expression in vivo and in vitro. J. Nutr. 146, 444S–449S (2016)Google Scholar
  16. 16.
    U.M. Kocyigit, Y. Budak, M.B. Gürdere, Ş Tekin, T. Kul Köprülü, F. Ertürk, K. Özcan, İ Gülçin, M. Ceylan, Synthesis, characterization, anticancer, antimicrobial and carbonic anhydrase inhibition profiles of novel (3aR,4S,7R,7aS)-2-(4-((E)-3-(3-aryl)acryloyl) phenyl)-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione derivatives. Bioorg. Chem. 70, 118–125 (2017)Google Scholar
  17. 17.
    J. Tuomilehto, D. Rastenyte, Q. Qiao, N.C. Barengo, K. Matz, Epidemiology of macrovascular disease and hypertension in diabetes mellitus. International Textbook of Diabetes Mellitus, Fourth Edition. Wiley, New York, 1005–1030 (2015)Google Scholar
  18. 18.
    P. Taslimi, H.E. Aslan, Y. Demir, N. Öztaşkın, A. Maraş, İ Gulçin, Ş Beydemir, Ş Göksu, Diarilmethanon, bromophenols and diarilmetan compounds: discovery of potent aldose reductase, α-amylase and α-glycosidase inhibitors as new therapeutic approach in diabetes and functional hyperglycemia. Int. J. Biol. Macromol. 119, 857–863 (2018)Google Scholar
  19. 19.
    H. Ali, P.J. Houghton, A. Soumyanath, Alpha-amylase inhibitory activity of some Malaysian plants used to treat diabetes; with particular reference to Phyllanthus amarus. J. Ethnopharmacol. 107, 449–455 (2006)Google Scholar
  20. 20.
    M. Zengin, H. Genç, P. Taslimi, A. Kestane, E. Güçlü, A. Ögütlü, O. Karabay, I. Gulcin, Novel thymol bearing oxypropanolamine derivatives as potent some metabolic enzyme inhibitors-their antidiabetic, anticholinergic and antibacterial potentials. Bioorg. Chem. 81, 119–126 (2018)Google Scholar
  21. 21.
    I. Gulcin, P. Taslimi, A. Aygün, N. Sadeghian, E. Bastem, Öİ Küfrevioğlu, F. Turkan, F. Şen, Antidiabetic and antiparasitic potentials: inhibition effects of some natural antioxidant compounds on α-glycosidase, α-amylase and human glutathione S-transferase enzymes. Int. J. Biol. Macromol. 119, 741–746 (2018)Google Scholar
  22. 22.
    F. Türker, D. Barut Celepci, A. Aktaş, P. Taslimi, Y. Gök, M. Aygün, İ Gulçin, Meta-cyanobenzyl substituted benzimidazole: synthesis, characterization, crystal structure and carbonic anhydrase, α-glycosidase, butyrylcholinesterase, acetylcholinesterase inhibitory properties. Arch. Pharm. 351(7), e201800029 (2018)Google Scholar
  23. 23.
    M.A. Butala, S.K. Kukkupuni, C.N. Vishnuprasad, Ayurvedic anti-diabetic formulation Lodhrasavam inhibits alpha-amylase, alpha-glucosidase and suppresses adipogenic activity in vitro. J. Ayurveda Integr. Med. 8, 145–151 (2017)Google Scholar
  24. 24.
    S. Burmaoglu, A.O. Yilmaz, P. Taslimi, O. Algul, D. Kılıç, I. Gulcin, Synthesis and biological evaluation of phloroglucinol derivatives possessing α-glycosidase, acetylcholinesterase, butyrylcholinesterase, carbonic anhydrase inhibitory activity. Arch. Pharm. 351(2), e1700314 (2018)Google Scholar
  25. 25.
    J. Godyń, J. Jończyk, D. Panek, B. Malawska, Therapeutic strategies for Alzheimer’s disease in clinical trials. Pharmacol. Rep. 68, 127–138 (2016)Google Scholar
  26. 26.
    H. Hampel, M.M. Mesulam, A.C. Cuello, M.R. Farlow, E. Giacobini, G.T. Grossberg, A.S. Khachaturian, A. Vergallo, E. Cavedo, P.J. Snyder, Z.S. Khachaturian, The cholinergic system in the pathophysiology and treatment of Alzheimer’s disease. Brain 141, 1917–1933 (2018)Google Scholar
  27. 27.
    D. Galimberti, E. Scarpini, Old and new acetylcholinesterase inhibitors for Alzheimer’s disease. Exp. Opin. Invest. Drugs 25, 1181–1187 (2016)Google Scholar
  28. 28.
    U.M. Koçyiğit, Y. Budak, M.B. Gürdere, F. Ertürk, B. Yencilek, P. Taslimi, İ Gulçin, M. Ceylan, Synthesis of chalcone-imide derivatives and investigation of their anticancer and antimicrobial activities, carbonic anhydrase and acetylcholinesterase enzymes inhibition profiles. Arch. Physiol. Biochem. 124, 61–68 (2018)Google Scholar
  29. 29.
    C.C. Tan, J.T. Yu, H.F. Wang, M.S. Tan, X.F. Meng, C. Wang, T. Jiang, X.C. Zhu, L. Tan, Efficacy and safety of donepezil, galantamine, rivastigmine, and memantine for the treatment of Alzheimer’s disease: a systematic review and meta-analysis. J. Alzheimers Dis. 41, 615–631 (2014)Google Scholar
  30. 30.
    Y. Sarı, A. Aktaş, P. Taslimi, Y. Gök, C. Caglayan, I. Gulcin, Novel N-propylphthalimide and 4-vinylbenzyl substituted benzimidazole salts: synthesis, characterization and determination of their metal chelating effects and inhibition profiles against acetylcholinesterase, and carbonic anhydrase enzymes. J. Biochem. Mol. Toxicol. 32(1), e22009 (2018)Google Scholar
  31. 31.
    M. Mathew, S. Subramanian, In vitro screening for anti-cholinesterase and antioxidant activity of methanolic extracts of ayurvedic medicinal plants used for cognitive disorders. PLoS ONE 9(1) (2014)Google Scholar
  32. 32.
    I. Gulcin, Antioxidant activity of food constituents: an overview. Arch. Toxicol. 86, 345–391 (2012)Google Scholar
  33. 33.
    I. Gulcin, Comparison of in vitro antioxidant and antiradical activities of l-tyrosine and l-dopa. Amino Acids 32, 431–438 (2007)Google Scholar
  34. 34.
    E. Koksal, I. Gulcin, Antioxidant activity of cauliflower (Brassica oleracea L.). Turk. J. Agric. For. 32, 65–78 (2008)Google Scholar
  35. 35.
    H. Tohma, I. Gulcin, E. Bursal, A.C. Gören, S.H. Alwasel, E. Köksal, Antioxidant activity and phenolic compounds of ginger (Zingiber officinale Rosc.) determined by HPLC-MS/MS. J. Food Measure 11(2), 556–566 (2017)Google Scholar
  36. 36.
    A. Altay, S. Degirmenci, M. Korkmaz, M. Cankaya, E. Koksal, In vitro evaluation of antioxidant and anti-proliferative activities of Gypsophila sphaerocephala (Caryophyllaceae) extracts together with their phenolic profiles. J. Food Measure 12, 2936–2945 (2018)Google Scholar
  37. 37.
    V.L. Singleton, J.A. Rossi, Colorimetry of total phenolics with phosphomolybdic-phosphotungstic acid reagents. Am. J. Enol. Viticul. 16, 144–158 (1965)Google Scholar
  38. 38.
    E. Bursal, I. Gulcin, Polyphenol contents and in vitro antioxidant activities of lyophilized aqueous extract of kiwifruit (Actinidia deliciosa). Food Res. Int. 44(5), 1482–1489 (2011)Google Scholar
  39. 39.
    I. Gulcin, M. Elmastas, H.Y. Aboul-Enein, Determination of antioxidant and radical scavenging activity of basil (Ocimum basilicum) assayed by different methodologies. Phytother. Res. 21, 354–361 (2007)Google Scholar
  40. 40.
    C.C. Chang, M.H. Yang, H.M. Wen, J.C. Chern, Estimation of total flavonoid content in propolis by two complementary colorimetric methods. J. Food Drugs Anal. 10, 178–182 (2002)Google Scholar
  41. 41.
    E. Köksal, E. Bursal, I. Gulcin, M. Korkmaz, C. Çağlayan, A.C. Gören, S.H. Alwasel Antioxidant activity and polyphenol content of Turkish thyme (Thymus vulgaris) monitored by liquid chromatography and tandem mass spectrometry. Int. J. Food Propert. 20(3), 514–525 (2016)Google Scholar
  42. 42.
    I. Gulcin, E. Bursal, H.M. Şehitoğlu, M. Bilsel, A.C. Gören, Polyphenol contents and antioxidant activity of lyophilized aqueous extract of propolis from Erzurum, Turkey. Food Chem. Toxicol. 48, 2227–2238 (2010)Google Scholar
  43. 43.
    I. Gulcin, F. Topal, S.B. Oztürk Sarikaya, E. Bursal, A.C. Gören, M. Bilsel, Polyphenol contents and antioxidant properties of medlar (Mespilus germanica L.). Rec. Nat. Prod. 5(3), 158–175 (2011)Google Scholar
  44. 44.
    A.C. Gören, S. Çıkrıkçı, M. Çergel, G. Bilsel, Rapid quantitation of curcumin in turmeric via NMR and LC-tandem mass spectrometry. Food Chem. 113, 1239–1242 (2009)Google Scholar
  45. 45.
    H. Han, H. Yılmaz, I. Gulcin, Antioxidant activity of flaxseed (Linum usitatissimum L.) and analysis of ıts polyphenol contents by LC-MS/MS. Rec. Nat. Prod. 12(4), 397–402 (2018)Google Scholar
  46. 46.
    H.O. Hamad, M.H. Alma, I. Gulcin, M.A. Yılmaz, E. Karaoğul, Evaluation of phenolic contents and bioactivity of root and nutgall extracts from Iraqian Quercus infectoria Olivier. Rec. Nat. Prod. 11(2), 205–210 (2017)Google Scholar
  47. 47.
    Z. Banikazemi, H.A. Haji, M. Mohammadi, G. Taheripak, E. Iranifar, M. Poursadeghiyan, A. Moridikia, B. Rashidi, M. Taghizadeh, H. Mirzaei, Diet and cancer prevention: dietary compounds, dietary microRNAs, and dietary exosomes. J. Cell. Biochem. 119, 185–196 (2018)Google Scholar
  48. 48.
    I.R. Kubra, L.J. Rao, An impression on current developments in the technology, chemistry, and biological activities of ginger (Zingiber officinale Roscoe). Crit. Rev. Food. Sci. Nutr. 52, 651–688 (2012)Google Scholar
  49. 49.
    J.C. Lee, J. Kim, Y.S. Jang, Ethanol eluted extract of Rhus verniciflua Stokes showed both antioxidant and cytotoxic effects on mouse thymocytes depending on the dose and time of the treatment. J. Biochem. Mol. Biol. 36(3), 337–343 (2001)Google Scholar
  50. 50.
    J.C. Lee, K.Y. Lee, J. Kim, C.S. Na, N.C. Jung, G.H. Chung, Y.S. Jang. Extract from Rhus verniciflua stokes is capable of inhibiting the growth of human lymphoma cells. Food Chem. Toxicol. 42, 1383–1388 (2004)Google Scholar
  51. 51.
    H.S. Choi, M.K. Kim, Y.K. Choi, Y.C. Shin, S.G. Cho, S.G. Ko, Rhus verniciflua stokes (RVS) and butein induce apoptosis of paclitaxel-resistant SKOV-3/PAX ovarian cancer cells through inhibition of AKT phosphorylation. BMC Comp. Altern. Med. 16, 122 (2016)Google Scholar
  52. 52.
    T. Hiyoshi, M. Fujiwara, Z. Yao, Postprandial hyperglycemia and postprandial hypertriglyceridemia in type 2 diabetes. J. Biomed. Res. (2017)Google Scholar
  53. 53.
    F. Ismail-Beigi, Clinical practice. Glycemic management of type 2 diabetes mellitus. N. Engl. J. Med. 366, 1319–1327 (2012)Google Scholar
  54. 54.
    S.E. Inzucchi, R.M. Bergenstal, J.B. Buse, M. Diamant, E. Ferrannini, M. Nauck, A.L. Peters, A. Tsapas, R. Wender, D.R. Matthews, Management of hyperglycaemia in type 2 diabetes, 2015: a patient-centred approach. Update to a position statement of the American diabetes association and the european association for the study of diabetes. Diabetologia 58, 429–442 (2015)Google Scholar
  55. 55.
    N. Orhan, M. Aslan, M. Süküroğlu, O.D. Deliorman, In vivo and in vitro antidiabetic effect of Cistus laurifolius L. and detection of major phenolic compounds by UPLC-TOF-MS analysis. J. Ethnopharmacol. 146, 859–865 (2013)Google Scholar
  56. 56.
    Z. Zhang, J. Jiang, P. Yu, X. Zeng, J.W. Larrick, Y. Wang, Hypoglycemic and beta cell protective effects of andrographolide analogue for diabetes treatment. J. Transl. Med. 7, 62 (2009)Google Scholar
  57. 57.
    A. Ahangarpour, H. Heidari, M.S. Junghani, R. Absari, M. Khoogar, E. Ghaedi, Effects of hydroalcoholic extract of Rhus coriaria seed on glucose and insulin related biomarkers, lipid profile, and hepatic enzymes in nicotinamide-streptozotocin-induced type II diabetic male mice. Res. Pharm. Sci. 12, 416–424 (2017)Google Scholar
  58. 58.
    G. Gondolova, P. Taslimi, A. Medjidov, F. Farzaliyev, A. Sujayev, M. Huseuinova, O. Şahin, B. Yalçın, F. Turkan, I. Gulcin, Synthesis, crystal structure and biological evaluation of spectroscopic characterization of Ni(II) and Co(II) complexes with N-salicyloil-N′-maleoil-hydrazine as anticholinergic and antidiabetic agents. J. Biochem. Mol. Toxicol. 32(9), e22197 (2018)Google Scholar
  59. 59.
    M. Huseynova, P. Taslimi, A. Medjidov, V. Farzaliyev, M. Aliyeva, G. Gondolova, O. Şahin, B. Yalçın, A. Sujayev, E.B. Orman, A.R. Özkaya, I. Gulcin, Synthesis, characterization, crystal structure, electrochemical studies and biological evaluation of metal complexes with thiosemicarbazone of glyoxylic acid. Polyhedron 155, 25–33 (2018)Google Scholar
  60. 60.
    S. Giancarlo, L.M. Rosa, F. Nadjafi, M. Francesco, Hypoglycaemic activity of two spices extracts: Rhus coriaria L. and Bunium persicum Boiss. Nat. Prod. Res. 20, 882–886 (2006)Google Scholar
  61. 61.
    A. Prasansuklab, T. Tencomnao, Amyloidosis in Alzheimer’s disease: the toxicity of amyloid beta (A beta), mechanisms of its accumulation and implications of medicinal plants for therapy. Evid. Based Complement. Alternat. Med. 413808 (2013)Google Scholar
  62. 62.
    M.W. Jann, K.L. Shirley, G.W. Small, Clinical pharmacokinetics and pharmacodynamics of cholinesterase inhibitors. Clin. Pharm. 41, 719–739 (2002)Google Scholar
  63. 63.
    T.B. Ali, T.R. Schleret, B.M. Reilly, W.Y. Chen, R. Abagyan, Adverse effects of cholinesterase inhibitors in dementia, according to the pharmacovigilance databases of the United-States and Canada. PLoS ONE 10, e0144337 (2015)Google Scholar
  64. 64.
    A.K. Singhal, V. Naithani, O.P. Bangar, Medicinal plants with a potential to treat Alzheimer and associated symptoms. Int. J. Nutr. Pharmacol. Neurol. Dis. 2(2), 84 (2012)Google Scholar
  65. 65.
    E. Köksal, E. Bursal, E. Dikici, F. Tozoğlu, I. Gulcin, Antioxidant activity of Melissa officinalis leaves. J. Med. Plants Res. 5(2), 217–222 (2011)Google Scholar
  66. 66.
    M. Kosar, B. Bozan, F. Temelli, K.H.C. Baser, Antioxidant activity and phenolic composition of sumac (Rhus coriaria L.) extracts. Food Chem. 103, 952–959 (2007)Google Scholar
  67. 67.
    R. Kossah, C. Nsabimana, H. Zhang, W. Chen, Optimization of extraction of polyphenols from Syrian sumac (Rhus coriaria L.) and Chinese sumac (Rhus typhina L.) fruits. Res. J. Phytochem. 4, 146–153 (2010)Google Scholar
  68. 68.
    I. Gulcin, Antioxidant activity of L-adrenaline: an activity-structure insight. Chem. Biol. Interact. 179, 71–80 (2009)Google Scholar
  69. 69.
    T. Ak, I. Gulcin, Antioxidant and radical scavenging properties of curcumin. Chem. Biol. Interact. 174, 27–37 (2008)Google Scholar
  70. 70.
    I. Gulcin, R. Elias, A. Gepdiremen, L. Boyer, E. Köksal, A comparative study on the antioxidant activity of fringe tree (Chionanthus virginicus L.) extracts. Afr. J. Biotechnol. 6(4), 410–418 (2007)Google Scholar
  71. 71.
    M.S. Stanković, M. Petrović, D. Godjevac, Z.D. Stevanović, Screening inland halophytes from the central Balkan for their antioxidant activity in relation to total phenolic compounds and flavonoids: are there any prospective medicinal plants? J. Arid Environ. 120, 26–32 (2015)Google Scholar
  72. 72.
    N. Trabelsi, W. Megdiche, R. Ksouri, H. Falleh, S. Oueslati, B. Soumaya, H. Hajlaoui, C. Abdelly, Solvent effects on phenolic contents and biological activities of the halophyte Limoniastrum monopetalum leaves. Lebensm. Wissen. Technol. 43, 632–639 (2010)Google Scholar
  73. 73.
    E. Hayouni, M. Abedrabba, M. Bouix, M. Hamdi, The effects of solvents and extraction method on the phenolic contents and biological activities in vitro of Tunisian Quercus coccifera L. and Juniperus phoenicea L. fruit extracts. Food Chem. 105, 1126–1134 (2007)Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Hatice Tohma
    • 1
  • Ahmet Altay
    • 1
  • Ekrem Köksal
    • 1
    Email author
  • Ahmet Ceyhan Gören
    • 2
  • İlhami Gülçin
    • 3
  1. 1.Faculty of Science, Department of ChemistryErzincan Binali Yıldırım UniversityErzincanTurkey
  2. 2.Faculty of Pharmacy, Department of Basic Pharmaceutical SciencesBezmialem Vakif UniversityFatihTurkey
  3. 3.Faculty of Science, Department of ChemistryAtatürk UniversityErzurumTurkey

Personalised recommendations