Generic placeholder image

The Natural Products Journal

Author(s): Hüseyin Akşit*, Erdem Ozan and Ramazan Erenler

DOI: 10.2174/2210315513666221125142944

DownloadDownload PDF Flyer Cite As
Isolation, Characterization, and Antiproliferative Activity of Polymethoxy Flavones from Mentha dumetorum

Article ID: e251122211271 Pages: 7

  • * (Excluding Mailing and Handling)

Explore Articles
About Journal
For Authors
For Editors
For Reviewers

Abstract

Background: Natural products have been used commonly in the pharmaceutical industry as well as traditional medicine due to their bioactive contents.

Objective: The objective of this study is to isolate the polymethoxy flavones (PMFs) and evaluate the antiproliferative activity.

Methods: The PMFs were extracted from Mentha dumetorum with boiling hot water and then partitioned with hexane and the extract was subjected to chromatographic techniques such as Sephadex LH-20, silica gel, and preparative TLC, and HPLC to isolate the compounds. The structures of isolated compounds were elucidated by spectroscopic techniques such as 1H-NMR, 13C-NMR, LC-TOF-MS, and UV-Vis. The antiproliferative effects of isolated compounds were evaluated using a real-time cell analyzer–single plate (RTCA-SP) instrument against HeLa and HT29 cell lines.

Results: The isolated PMFs were identified as xanthomicrol (1), 5-hydroxy-6,7,8,4'-tetrametoxy flavanone (2), 5-desmetil sinensetin (3), 5-demetil nobiletin (4), gardenin B (5), 5-hydroxy-6,7,8,3',4'- penta methoxy flavanone (6) and 5-hydroxy-6,7,4'-trimethoxy flavone (7). Compounds 2 and 5 were found to be the most active against both cell lines.

Conclusion: The isolated compounds as well as the plant extract of Mentha dumetorum could be promising agents for the drug development process, especially drugs for cancer treatment. Moreover, isolation methods were developed for the corresponding compounds.

Graphical Abstract

[1]
Topçu, G.; Erenler, R.; Çakmak, O.; Johansson, C.B.; Çelik, C.; Chai, H.B.; Pezzuto, J.M. Diterpenes from the berries of Juniperus excelsa. Phytochemistry, 1999, 50(7), 1195-1199.
[http://dx.doi.org/10.1016/S0031-9422(98)00675-X] [PMID: 10234860]
[2]
Elmastas, M.; Ozturk, L.; Gokce, I.; Erenler, R.; Aboul-Enein, H.Y. Determination of antioxidant activity of marshmallow flower (Althaea officinalis L.). Anal. Lett., 2004, 37(9), 1859-1869.
[http://dx.doi.org/10.1081/AL-120039431]
[3]
Demirtas, I.; Erenler, R.; Elmastas, M.; Goktasoglu, A. Studies on the antioxidant potential of flavones of Allium vineale isolated from its water-soluble fraction. Food Chem., 2013, 136(1), 34-40.
[http://dx.doi.org/10.1016/j.foodchem.2012.07.086] [PMID: 23017389]
[4]
Yaglıoglu, A.S.; Akdulum, B.; Erenler, R.; Demirtas, I.; Telci, I.; Tekin, S. Antiproliferative activity of pentadeca-(8E, 13Z) dien-11-yn-2-one and (E)-1,8-pentadecadiene from Echinacea pallida (Nutt.) Nutt. roots. Med. Chem. Res., 2013, 22(6), 2946-2953.
[http://dx.doi.org/10.1007/s00044-012-0297-2]
[5]
Erenler, R.; Yilmaz, S.; Aksit, H.; Sen, O.; Genc, N.; Elmastas, M.; Demirtas, I. Antioxidant activities of chemical constituents isolated from Echinops orientalis Trauv. Rec. Nat. Prod., 2014, 8(1), 32-36.
[6]
Kaya, G.; Karakaya, R.; Tilgel, E.; Sandikci, M.; Yucel, E.; Cicek, G.; Kayir, O.; Aksit, H.; Telci, I.; Guzel, A. Essential oil constituents of Thuja orientalis berries. J. New Res. Sci., 2014, 7(7), 1-6.
[7]
Elmastaş, M.; Telci, İ.; Akşit, H.; Erenler, R. Comparison of total phenolic contents and antioxidant capacities in mint genotypes used as spices/Baharat olarak kullanılan nane genotiplerinin toplam fenolik içerikleri ve antioksidan kapasitelerinin karşılaştırılması. Turk Biyokim. Derg., 2015, 40(6), 456-462.
[http://dx.doi.org/10.1515/tjb-2015-0034]
[8]
Erenler, R.; Sen, O.; Aksit, H.; Demirtas, I.; Yaglioglu, A.S.; Elmastas, M.; Telci, İ. Isolation and identification of chemical constituents from Origanum majorana and investigation of antiproliferative and antioxidant activities. J. Sci. Food Agric., 2016, 96(3), 822-836.
[http://dx.doi.org/10.1002/jsfa.7155] [PMID: 25721137]
[9]
Erenler, R.; Telci, I.; Ulutas, M.; Demirtas, I.; Gul, F.; Elmastas, M.; Kayir, O. Chemical constituents, quantitative analysis and antioxidant activities of E. chinacea purpurea (L.) Moench and E. chinacea pallida (Nutt.) Nutt. J. Food Biochem., 2015, 39(5), 622-630.
[http://dx.doi.org/10.1111/jfbc.12168]
[10]
Tarimcilar, G.; Yilmaz, Ö.; Daskin, R.; Kaynak, G. Nutlet morphology and its taxonomic significance in the genus Mentha L. (Lamiaceae) from Turkey. Bangladesh J. Plant Taxon., 2013, 20(1), 9-18.
[http://dx.doi.org/10.3329/bjpt.v20i1.15459]
[11]
Fagbemi, B.; Morton, J. Studies on Mentha×dumetorum Schult. (Labiatae) to confirm its presumed parentage-M. aquatica Linn.× M. longifolia (Linn.) Huds. Rhodora, 1982, 84(839), 439-445.
[12]
Sachan, A.; Kumar, S.; Kumari, K.; Singh, D. Medicinal uses of spices used in our traditional culture: Worldwide. J. Med. Plants Stud., 2018, 6(3), 116-122.
[13]
Walle, T. In Seminars in cancer biology; Elsevier, 2007, Vol. 17, pp. 354-362.
[14]
Manthey, J.; Guthrie, N.; Grohmann, K. Biological properties of citrus flavonoids pertaining to cancer and inflammation. Curr. Med. Chem., 2001, 8(2), 135-153.
[http://dx.doi.org/10.2174/0929867013373723] [PMID: 11172671]
[15]
Anagnostopoulou, M.A.; Kefalas, P.; Kokkalou, E.; Assimopoulou, A.N.; Papageorgiou, V.P. Analysis of antioxidant compounds in sweet orange peel by HPLC-diode array detection-electrospray ionization mass spectrometry. Biomed. Chromatogr., 2005, 19(2), 138-148.
[http://dx.doi.org/10.1002/bmc.430] [PMID: 15515108]
[16]
Kobayashi, S.; Tanabe, S. Evaluation of the anti-allergic activity of Citrus unshiu using rat basophilic leukemia RBL-2H3 cells as well as basophils of patients with seasonal allergic rhinitis to pollen. Int. J. Mol. Med., 2006, 17(3), 511-515.
[http://dx.doi.org/10.3892/ijmm.17.3.511] [PMID: 16465400]
[17]
Tang, M.; Ogawa, K.; Asamoto, M.; Hokaiwado, N.; Seeni, A.; Suzuki, S.; Takahashi, S.; Tanaka, T.; Ichikawa, K.; Shirai, T. Protective effects of citrus nobiletin and auraptene in transgenic rats developing adenocarcinoma of the prostate (TRAP) and human prostate carcinoma cells. Cancer Sci., 2007, 98(4), 471-477.
[http://dx.doi.org/10.1111/j.1349-7006.2007.00417.x] [PMID: 17284254]
[18]
Yoshimizu, N.; Otani, Y.; Saikawa, Y.; Kubota, T.; Yoshida, M.; Furukawa, T.; Kumai, K.; Kameyama, K.; Fujii, M.; Yano, M.; Sato, T.; Ito, A.; Kitajima, M. Anti-tumour effects of nobiletin, a citrus flavonoid, on gastric cancer include: antiproliferative effects, induction of apoptosis and cell cycle deregulation. Aliment. Pharmacol. Ther., 2004, 20(Suppl. 1), 95-101.
[http://dx.doi.org/10.1111/j.1365-2036.2004.02082.x] [PMID: 15298613]
[19]
Ohnishi, H.; Asamoto, M.; Tujimura, K.; Hokaiwado, N.; Takahashi, S.; Ogawa, K.; Kuribayashi, M.; Ogiso, T.; Okuyama, H.; Shirai, T. Inhibition of cell proliferation by nobiletin, a dietary phytochemical, associated with apoptosis and characteristic gene expression, but lack of effect on early rat hepatocarcinogenesis in vivo. Cancer Sci., 2004, 95(12), 936-942.
[http://dx.doi.org/10.1111/j.1349-7006.2004.tb03180.x] [PMID: 15596041]
[20]
Jin, Y.; Sui, D.; Li, X.; Yu, X.; Gui, M. Use of flavone and flavanone derivatives in preparation of sedative and hypnotic drugs. US2015/196529, 2015.
[21]
Tarawneh, A.; León, F.; Pettaway, S.; Elokely, K.M.; Klein, M.L.; Lambert, J.; Mansoor, A.; Cutler, S.J. Flavonoids from Perovskia atriplicifolia and their in vitro displacement of the respective radioligands for human opioid and cannabinoid receptors. J. Nat. Prod., 2015, 78(6), 1461-1465.
[http://dx.doi.org/10.1021/acs.jnatprod.5b00218] [PMID: 26035635]
[22]
Li, S.; Lo, C.Y.; Ho, C.T. Hydroxylated polymethoxyflavones and methylated flavonoids in sweet orange (Citrus sinensis) peel. J. Agric. Food Chem., 2006, 54(12), 4176-4185.
[http://dx.doi.org/10.1021/jf060234n] [PMID: 16756344]
[23]
Barberán, F.A.T.; Tomás, F.; Núñez, J.M. Seasonal variation of free flavone aglycones from Sideritis leucantha (Lamiaceae). Z. Naturforsch. C J. Biosci., 1985, 40(11-12), 914-916.
[http://dx.doi.org/10.1515/znc-1985-11-1228]
[24]
Urcan, E.; Haertel, U.; Styllou, M.; Hickel, R.; Scherthan, H.; Reichl, F.X. Real-time xCELLigence impedance analysis of the cytotoxicity of dental composite components on human gingival fibroblasts. Dent. Mater., 2010, 26(1), 51-58.
[http://dx.doi.org/10.1016/j.dental.2009.08.007] [PMID: 19767088]
[25]
Koldaş, S.; Demirtas, I.; Ozen, T.; Demirci, M.A.; Behçet, L. Phytochemical screening, anticancer and antioxidant activities of Origanum vulgare L. ssp. viride (Boiss.) Hayek, a plant of traditional usage. J. Sci. Food Agric., 2015, 95(4), 786-798.
[http://dx.doi.org/10.1002/jsfa.6903] [PMID: 25200133]
[26]
Aksit, H.; Çelik, S.M.; Sen, Ö.; Erenler, R.; Demirtas, I.; Telci, İ.; Elmastas, M. Complete isolation and characterization of polar portion of Mentha dumetorum water extract. Rec. Nat. Prod., 2014, 8(3), 277.
[27]
Tewari, N.; Mukharya, D. Isolation and study of new Gardenia glycoside Gardenin-5-O-β-D-glucopyranoside from the stem of Gardenia florida (Linn). Natl. Acad. Sci. Lett., 1988, 11, 281-282.
[28]
Nieto, M.; Gianello, J.; Tonn, C. Chemical components of 3 species of Parastrephia genus. An Asoc Quim Argent, 1994, 82(2), 105-109.
[29]
Parmar, V.S.; Bisht, K.S.; Sharma, S.K.; Jain, R.; Taneja, P.; Singh, S.; Simonsen, O.; Boll, P.M. Highly oxygenated bioactive flavones from Tamarix. Phytochemistry, 1994, 36(2), 507-511.
[http://dx.doi.org/10.1016/S0031-9422(00)97104-8]
[30]
Grayer, R.J.; Bryan, S.E.; Veitch, N.C.; Goldstone, F.J.; Paton, A.; Wollenweber, E. External flavones in sweet basil, Ocimum basilicum, and related taxa. Phytochemistry, 1996, 43(5), 1041-1047.
[http://dx.doi.org/10.1016/S0031-9422(96)00430-X] [PMID: 8987875]
[31]
Areias, F.M.; Valentão, P.; Andrade, P.B.; Ferreres, F.; Seabra, R.M. Phenolic fingerprint of peppermint leaves. Food Chem., 2001, 73(3), 307-311.
[http://dx.doi.org/10.1016/S0308-8146(00)00302-2]
[32]
Kawaii, S.; Ikuina, T.; Hikima, T.; Tokiwano, T.; Yoshizawa, Y. Relationship between structure and antiproliferative activity of polymethoxyflavones towards HL60 cells. Anticancer Res., 2012, 32(12), 5239-5244.
[PMID: 23225422]
[33]
Akao, Y.; itoh, T.; Ohguchi, K.; Iinuma, M.; Nozawa, Y. Interactive effects of polymethoxy flavones from Citrus on cell growth inhibition in human neuroblastoma SH-SY5Y cells. Bioorg. Med. Chem., 2008, 16(6), 2803-2810.
[http://dx.doi.org/10.1016/j.bmc.2008.01.058] [PMID: 18282757]