Abstract
Helichrysum plicatum species are used in Turkish folk medicine as lithagogue, diuretic, and nephritic. Research on the methanol (MeOH) extract of flowers of H. plicatum DC. subsp. plicatum resulted in the isolation of eight known compounds (1–8). The chemical structures of the compounds were determined as β-sitosterol (1), apigenin (2), nonacosanoic acid (3), astragalin (4), β-sitosterol-3-O-β-D-glucopyranoside (5), helichrysin A (6), helichrysin B (7), and isosalipurposide (8) by spectroscopic and chromatographic/spectrometric methods, including 1D and 2D nuclear magnetic resonance and liquid chromatography-tandem mass spectrometry. Nonacosanoic acid (3) was isolated for the first time from H. plicatum DC. subsp. plicatum. The MeOH extract and isolated compounds were evaluated for their in vitro human carbonic anhydrase I (hCAI) and II (hCAII), acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and α-glycosidase inhibitory activities. The IC50 values of H. plicatum DC. subsp. plicatum MeOH extract for hCAI, hCAII, AChE, BChE, and α-glycosidase were found to be 77.87, 52.90, 115.50, 117.46, and 81.53 mg/mL, respectively. The compounds showed IC50 values of 1.43–4.47, 1.40–4.32, 1.69–2.90, 1.09–3.89, and 1.61–3.80 μM against hCAI, hCAII, AChE, BChE, and α-glycosidase, respectively. In summary, H. plicatum DC. subsp. plicatum secondary metabolites demonstrated strong inhibitory effects especially against hCAI and hCAII, whereas the MeOH extract showed a weak inhibitory effect on all enzymes.
Acknowledgments
The author is grateful for the support of Dr. Ahmet Cakir in structure characterization, Dr. Cavit Kazaz in NMR spectral measurements, and Ruya Kaya in biochemistry assays.
References
1. Bayir Y, Halici Z, Keles MS, Colak S, Cakir A, Kaya Y, et al. Helichrysum plicatum DC. subsp plicatum extract as a preventive agent in experimentally induced urolithiasis model. J Ethnopharmacol 2011;138:408–14.10.1016/j.jep.2011.09.026Search in Google Scholar PubMed
2. Ozturk B, Ozek G, Ozek T, Baser KH. Chemical diversity in volatiles of Helichrysum plicatum DC. subspecies in Turkey. Rec Nat Prod 2014;8:373–84.Search in Google Scholar
3. Aslan M, Orhan DD, Orhan N, Sezik E, Yesilada E. In vivo antidiabetic and antioxidant potential of Helichrysum plicatum ssp plicatum capitulums in streptozotocin-induced-diabetic rats. J Ethnopharmacol 2007;109:54–9.10.1016/j.jep.2006.07.001Search in Google Scholar PubMed
4. Ozbek T, Gulluce M, Adiguzel A, Ozkan H, Sahin F, Orhan F. Antimutagenic activity of the methanol extract of Helichrysum plicatum ssp plicatum. Asian J Chem 2009;21:2705–10.Search in Google Scholar
5. Karaca M, Ozbek H, Akkan HA, Tutuncu M, Ozgokce F, Him A, et al. Anti-inflammatory activities of diethyl-ether extracts of Helichrysum plicatum DC. and Tanacetum balsamita L. in rats. Asian J Anim Vet Adv 2009;4:320–5.10.3923/ajava.2009.320.325Search in Google Scholar
6. Demir A, Taban BM, Aslan M, Yesilada E, Aytac SA. Antimicrobial effect of Helichrysum plicatum subsp plicatum. Pharm Biol 2009;47:289–97.10.1080/13880200802590434Search in Google Scholar
7. Tatli II, Sahpaz S, Akkol EK, Martin-Nizard F, Gressier B, Ezer N, et al. Antioxidant, anti-inflammatory, and antinociceptive activities of Turkish medicinal plants. Pharm Biol 2009;47:916–21.10.1080/13880200902962731Search in Google Scholar
8. Turker H, Yildirim AB, Karakas FP. Sensitivity of bacteria isolated from fish to some medicinal plants. Turk J Fish Aquat Sci 2009;9:181–6.10.4194/trjfas.2009.0209Search in Google Scholar
9. Apaydin Yildirim B, Kordali S, Terim Kapakin KA, Yildirim F, Aktas Senocak E, Altun S. Effect of Helichrysum plicatum DC. subsp plicatum ethanol extract on gentamicin-induced nephrotoxicity in rats. J Zhejiang Univ Sci B 2017;18:501–11.10.1631/jzus.B1500291Search in Google Scholar PubMed PubMed Central
10. Kulevanova S, Stefova M, Stafilov T. HPLC identification and determination of flavone aglycones in Helichrysum plicatum DC. (Asteraceae). Pharmazie 2000;55:391–2.Search in Google Scholar
11. Bigovic DJ, Stevic TR, Jankovic TR, Noveski NB, Radanovic DS, Pljevljakusic DS, et al. Antimicrobial activity of Helichrysum plicatum DC. Hem Ind 2017;71:337–42.10.2298/HEMIND160118044BSearch in Google Scholar
12. Boztas M, Cetinkaya Y, Topal M, Gulcin I, Menzek A, Sahin E, et al. Synthesis and carbonic anhydrase isoenzymes I, II, IX, and XII inhibitory effects of dimethoxybromophenol derivatives incorporating cyclopropane moieties. J Med Chem 2015;58:640–50.10.1021/jm501573bSearch in Google Scholar PubMed
13. Topal M, Gulcin I. Rosmarinic acid: a potent carbonic anhydrase isoenzymes inhibitor. Turk J Chem 2014;38:894–902.10.3906/kim-1403-5Search in Google Scholar
14. Arabaci B, Gulcin I, Alwasel S. Capsaicin: a potent inhibitor of carbonic anhydrase isoenzymes. Molecules 2014;19:10103–14.10.3390/molecules190710103Search in Google Scholar PubMed PubMed Central
15. Bal S, Kaya R, Gok Y, Taslimi P, Aktas A, Karaman M, et al. Novel 2-methylimidazolium salts: synthesis, characterization, molecular docking, and carbonic anhydrase and acetylcholinesterase inhibitory properties. Bioorg Chem 2020;94:1–10.10.1016/j.bioorg.2019.103468Search in Google Scholar PubMed
16. Taslimi P, Turkan F, Cetin A, Burhan H, Karaman M, Bildirici I, et al. Pyrazole[3,4-d]pyridazine derivatives: molecular docking and explore of acetylcholinesterase and carbonic anhydrase enzymes inhibitors as anticholinergics potentials. Bioorg Chem 2019;92:1–8.10.1016/j.bioorg.2019.103213Search in Google Scholar PubMed
17. Maren TH. The development of topical carbonic anhydrase inhibitors. J Glaucoma 1995;4:49–62.10.1097/00061198-199502000-00012Search in Google Scholar
18. El-Azab AS, Abdel-Aziz AA, Bua S, Nocentini A, Alanazi MM, AlSaif NA, et al. Synthesis and comparative carbonic anhydrase inhibition of new Schiff’s bases incorporating benzenesulfonamide, methanesulfonamide, and methylsulfonylbenzene scaffolds. Bioorg Chem 2019;92:1–8.10.1016/j.bioorg.2019.103225Search in Google Scholar PubMed
19. Cakmak KC, Gulcin I. Anticholinergic and antioxidant activities of usnic acid – an activity-structure insight. Toxicol Rep 2019;6:1273–80.10.1016/j.toxrep.2019.11.003Search in Google Scholar PubMed PubMed Central
20. Gulcin I, Goren AC, Taslimi P, Alwasel SH, Kilic O, Bursal E. Anticholinergic, antidiabetic and antioxidant activities of Anatolian pennyroyal (Mentha pulegium) – analysis of its polyphenol contents by LC-MS/MS. Biocatal Agric Biotechnol 2020;23:1–10.10.1016/j.bcab.2019.101441Search in Google Scholar
21. Yamali C, Gul HI, Kazaz C, Levent S, Gulcin I. Synthesis, structure elucidation, and in vitro pharmacological evaluation of novel polyfluoro substituted pyrazoline type sulfonamides as multi-target agents for inhibition of acetylcholinesterase and carbonic anhydrase I and II enzymes. Bioorg Chem 2020;96:1–8.10.1016/j.bioorg.2020.103627Search in Google Scholar PubMed
22. Taslimi P, Osmanova S, Caglayan C, Turkan F, Sardarova S, Farzaliyev V, et al. Novel amides of 1,1-bis-(carboxymethylthio)-1-arylethanes: synthesis, characterization, acetylcholinesterase, butyrylcholinesterase, and carbonic anhydrase inhibitory properties. J Biochem Mol Toxicol 2018;32:1–9.10.1002/jbt.22191Search in Google Scholar PubMed
23. Oztaskin N, Cetinkaya Y, Taslimi P, Goksu S, Gulcin I. Antioxidant and acetylcholinesterase inhibition properties of novel bromophenol derivatives. Bioorg Chem 2015;60:49–57.10.1016/j.bioorg.2015.04.006Search in Google Scholar PubMed
24. Turkan F. Investigation of the toxicological and inhibitory effects of some benzimidazole agents on acetylcholinesterase and butyrylcholinesterase enzymes. Arch Physiol Biochem 2019:1–5.10.1080/13813455.2019.1618341Search in Google Scholar
25. Mahmood W, Saleem H, Ahmad I, Ashraf M, Gill MS, Ahsan HM, et al. In-vitro studies on acetylcholinesterase and butyrylcholinesterase inhibitory potentials of aerial parts of Vernonia oligocephala (Asteraceae). Trop J Pharm Res 2018;17:2445–8.10.4314/tjpr.v17i12.20Search in Google Scholar
26. Burmaoglu S, Yilmaz AO, Polat MF, Kaya R, Gulcin I, Algul O. Synthesis and biological evaluation of novel tris-chalcones as potent carbonic anhydrase, acetylcholinesterase, butyrylcholinesterase and alpha-glucosidase inhibitors. Bioorg Chem 2019;85:191–7.10.1016/j.bioorg.2018.12.035Search in Google Scholar
27. Gulcin I, Taslimi P, Aygun A, Sadeghian N, Bastem E, Kufrevioglu OH, et al. Antidiabetic and antiparasitic potentials: inhibition effects of some natural antioxidant compounds on alpha-glucosidase, alpha-amylase and human glutathione S-transferase enzymes. Int J Biol Macromol 2018;119:741–6.10.1016/j.ijbiomac.2018.08.001Search in Google Scholar
28. Gondolova G, Taslimi P, Medjidov A, Farzaliyev V, Sujayev A, Huseynova M, et al. 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 2018;32:1–8.10.1002/jbt.22197Search in Google Scholar
29. Wang H, Wang J, Liu YJ, Ji YL, Guo YT, Zhao J. Interaction mechanism of carnosic acid against glycosidase (alpha-amylase and alpha-glucosidase). Int J Biol Macromol 2019;138:846–53.10.1016/j.ijbiomac.2019.07.179Search in Google Scholar
30. Aksu K, Akincioglu H, Akincioglu A, Goksu S, Tumer F, Gulcin I. Synthesis of novel sulfamides incorporating phenethylamines and determination of their inhibition profiles against some metabolic enzymes. Arch Pharm 2018;351:1–9.10.1002/ardp.201800150Search in Google Scholar
31. Verpoorte JA, Mehta S, Edsall JT. Esterase activities of human carbonic anhydrases B and C. J Biol Chem 1967;242:4221–9.10.1016/S0021-9258(18)95800-XSearch in Google Scholar
32. Taslimi P, Gulcin I. Antioxidant and anticholinergic properties of olivetol. J Food Biochem 2018;42:1–12.10.1111/jfbc.12516Search in Google Scholar
33. Ellman GL, Courtney KD, Andres V Jr, Feather-Stone RM. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 1961;7:88–95.10.1016/0006-2952(61)90145-9Search in Google Scholar
34. Taslimi P, Akincioglu H, Gulcin I. Synephrine and phenylephrine act as -amylase, -glycosidase, acetylcholinesterase, butyrylcholinesterase, and carbonic anhydrase enzymes inhibitors. J Biochem Mol Toxicol 2017;31:1–6.10.1002/jbt.21973Search in Google Scholar PubMed
35. Tao Y, Zhang YF, Cheng YY, Wang Y. Rapid screening and identification of alpha-glucosidase inhibitors from mulberry leaves using enzyme-immobilized magnetic beads coupled with HPLC/MS and NMR. Biomed Chromatogr 2013;27:148–55.10.1002/bmc.2761Search in Google Scholar PubMed
36. Aydin T, Cakir A, Kazaz C, Bayrak N, Bayir Y, Taskesenligil Y. Insecticidal metabolites from the rhizomes of Veratrum album against adults of Colorado potato beetle, Leptinotarsa decemlineata. Chem Biodivers 2014;11:1192–204.10.1002/cbdv.201300407Search in Google Scholar PubMed
37. Dehmoradkhani KR, Jafari A, Shokoohinia Y, Emami SA, Mojarrab M. Flavonoids from the aerial parts of Artemisia biennis Willd. Pharm Sci 2019;25:364–8.10.15171/PS.2019.33Search in Google Scholar
38. Yang NY, Liu L, Tao WW, Duan JA, Liu XH, Huang SP. Antithrombotic lipids from semen persicae. Nat Prod Res 2011;25:1650–6.10.1080/14786419.2011.568942Search in Google Scholar PubMed
39. Yi J, Wu JG, Wu YB, Peng W. Antioxidant and anti-proliferative activities of flavonoids from Bidens pilosa L. var radiata Sch Bip. Trop J Pharm Res 2016;15:341–8.10.4314/tjpr.v15i2.17Search in Google Scholar
40. Wright WG. South-African plant extractives. Part III. Helichrysin, a new chalcone glucoside from a Helichrysum species. JCS Perkin 1976;17:1819–20.10.1039/p19760001819Search in Google Scholar
41. Ghouila H, Meksi N, Haddar W, Mhenni MF, Jannet HB. Extraction, identification and dyeing studies of isosalipurposide, a natural chalcone dye from Acacia cyanophylla flowers on wool. Ind Crops Prod 2012;35:31–6.10.1016/j.indcrop.2011.05.026Search in Google Scholar
42. Teng H, Chen L, Fang T, Yuan BY, Lin QY. Rb2 inhibits alpha-glucosidase and regulates glucose metabolism by activating AMPK pathways in HepG2 cells. J Funct Foods 2017;28:306–13.10.1016/j.jff.2016.10.033Search in Google Scholar
43. Ekinci D, Karagoz L, Ekinci D, Senturk M, Supuran CT. Carbonic anhydrase inhibitors: in vitro inhibition of alpha isoforms (hCA I, hCA II, hCA III, hCA IV) by flavonoids. J Enzyme Inhib Med Chem 2013;28:283–8.10.3109/14756366.2011.643303Search in Google Scholar PubMed
44. Panche AN, Chandra S, Diwan AD. Multi-target beta-protease inhibitors from Andrographis paniculata: in silico and in vitro studies. Plants Basel 2019;8:1–28.Search in Google Scholar
45. Cheng N, Yi WB, Wang QQ, Peng SM, Zou XQ. Synthesis and alpha-glucosidase inhibitory activity of chrysin, diosmetin, apigenin, and luteolin derivatives. Chin Chem Lett 2014;25:1094–8.10.1016/j.cclet.2014.05.021Search in Google Scholar
46. Acet T, Ozcan K, Zengin G. An assessment of phenolic profiles, fatty acid compositions, and biological activities of two Helichrysum species: H. plicatum and H. chionophilum. J Food Biochem 2019:1–11.10.1111/jfbc.13128Search in Google Scholar PubMed
47. Gunes A, Kordali S, Turan M, Bozhuyuk AU. Determination of antioxidant enzyme activity and phenolic contents of some species of the Asteraceae family from medicanal plants. Ind Crop Prod 2019;137:208–13.10.1016/j.indcrop.2019.05.042Search in Google Scholar
©2020 Walter de Gruyter GmbH, Berlin/Boston
