Gökay ALBAYRAK, Serdar DEMİR, Halil KOYU, Sura BAYKAN

Anticholinesterase and antityrosinase activities of endemic Prangos heyniae H. Duman & M. F. Watson and its metabolites

Background and Aims: Prangos Lindl. (Apiaceae) are abundant in coumarins. Previously, along with n-hexane(HEX), chloroform(CHCl3), and methanol(MeOH) extracts, 8 molecules named osthol(1), isoimperatorin(2), oxypeucedanin(3), 7-methoxy-isoarnottinin-4'-O-β-ᴅ-glucopyranoside(4), 7-methoxy-isoarnottinin-4'-O-rutinoside(5), oxypeucedanin hydrate-3'-O-β-ᴅ-glucopyranoside(6), 1-methylethyl-6-O-D-apio-β-ᴅ-furanosyl-β-ᴅ-glucopyranoside(7), and cnidioside A(8) were obtained from the roots of endemic Prangos heyniae H. Duman & M. F. Watson. 4 and 5 were reported as novel compounds. Coumarins are known for their neuroprotective properties. Tyrosinase and cholinesterase enzymes play a key role in the course of neurodegenerative diseases such as Parkinson’s and Alzheimer’s disease(AD), respectively. Therefore, we aimed to evaluate the antityrosinase and anticholinesterase effects of the extracts and compounds 1-8 from Prangos heyniae roots. Methods: Tyrosinase and acetylcholinesterase-butyrylcholinesterase(AChE-BChE) inhibitory activities of the samples were evaluated spectrophotometrically. The screening of the samples was carried on at 1000 μg/mL. Results of triplicate analyses of the samples were given as IC50 values obtained through linear regression analysis. Kojic acid and galantamine were used as positive controls for antityrosinase and anticholinesterase experiments, respectively. Results: Only MeOH extract showed antityrosinase activity with an IC50 value of 543.37±7.45 μg/mL. CHCl3 extract exhibited both AChE and BChE inhibitory activities with IC50 values of 273.92 ± 32.07 and 38.68±2.56 μg/mL, respectively. Among tested compounds, 6 showed a weak BChE-specific inhibitory activity (IC50= 91.93±3.86μg/mL) and managed to possess 40 times inferior activity than galantamine(IC50= 2.25 ± 0.05μg/mL). Conclusion: The CHCl3 extract displayed a good BChE inhibitory activity. These findings suggested that Prangos heyniae could be a valuable natural source to develop novel BChE inhibitors with further studies against AD.

Keywords:

Prangos heyniae coumarin, anticholinesterase activity, antityrosinase activity, oxypeucedanin hydrate-3,

PDF

___

Abbas-Mohammadi, M., Farimani, M. M., Salehi, P., Ebrahimi, S. N., Sonboli, A., Kelso, C., & Skropeta, D. (2018). Acetylcholines- terase-inhibitory activity of Iranian plants: Combined HPLC/bio- assay-guided fractionation, molecular networking and docking strategies for the dereplication of active compounds. Journal of Pharmaceutical and Biomedical Analysis, 158, 471–479.
Ahmed, J., Güvenç, A., Küçükboyacı, N., Baldemir, A., & Coşkun, M. (2011). Total phenolic contents and antioxidant activities of Prangos Lindl.(Umbelliferae) species growing in Konya province (Turkey). Turkish Journal of Biology, 35(3), 353–360. https://doi. org/10.3906/biy-0809-23
Albayrak, G., Demir, S., Kose, F. A., & Baykan, S. (2021). New coumarin glycosides from endemic Prangos heyniae H. Duman & M.F. Watson. Natural Product Research, 1–13. https://doi.org/10.1080/14786419. 2021.1961138/SUPPL_FILE/GNPL_A_1961138_SM0346.DOCX
Albayrak, G., Demir, S., Koyu, H., & Baykan, S. (2022). Anticholinester- ase compounds from endemic Prangos uechtritzii. Chemistry & Bio- diversity, 19, e202200557. https://doi.org/10.1002/cbdv.202200557
Aytaç, Z., & Duman, H. (2016). Prangos abieticola (Apiaceae), a new species from south Anatolia, Turkey. Edinburgh Journal of Botany, 73(1), 125–131. https://doi.org/10.1017/S0960428615000293
Bahadori, M. B., Zengin, G., Bahadori, S., Maggi, F., & Dinparast, L. (2017). Chemical composition of essential oil, antioxidant, anti- diabetic, anti-obesity, and neuroprotective properties of Prangos gaubae. Natural Product Communications, 12(12), 1945–1948. https://doi.org/10.1177/1934578x1701201233
Başer, B., & Pehlivan, S. (2015). Türkiye’nin farklı bölgelerindeki Prangos Lindl . (Apiaceae) cinsine ait taksonların polenlerinin morfolojik farklılıkları. Bitlis Eren Üniversitesi Fen Bilimleri Dergisi, 4(2), 183–188. https://doi.org/10.17798/beufen.11965
Başer, K. H. C., Özek, T., Demirci, B., & Duman, H. (2000). Compo- sition of the essential oil of Prangos heyniae H. Duman et M. F. Watson, a new endemic from Turkey. Flavour and Fragrance Journal, 15(1), 47–49. https://doi.org/10.1002/(SICI)1099- 1026(200001/02)15:1<47::AID-FFJ869>3.0.CO;2-9
Behçet, L., Yapar, Y., & Olgun, Ş. (2019). Prangos aricakensis (Apiace- ae), a new species from eastern Turkey. Phytotaxa, 401(1), 55–63. https://doi.org/10.11646/phytotaxa.401.1.5
Bruno, M., Ilardi, V., Lupidi, G., Quassinti, L., Bramucci, M., Fiorini, D., … Maggi, F. (2021). Composition and biological activities of the essential oil from a Sicilian accession of Prangos ferulacea (L.) Lindl. Natural Product Research, 35(5), 733–743. https://doi.org/10.1080/14786419.2019.1598996
Bulut, G., Tuzlacı, E., Doğan, A., & Şenkardes, I. (2014). An ethno- pharmacological review on the Turkish Apiaceae species. Journal of Faculty Pharmacy of Istanbul University, 44(2), 163–179.
Chang, T. S. (2009). An updated review of tyrosinase inhibitors. International Journal of Molecular Sciences, 10(6), 2440–2475. https://doi.org/10.3390/ijms10062440
Dall’Acqua, S., Sut, S., Zengin, G., Peron, G., Elbasan, F., Yildiztugay, E., … Mahomoodally, M. F. (2022). Phytochemical screening, anti- oxidant, and enzyme inhibitory properties of three Prangos species (P. heyniae, P. meliocarpoides var. meliocarpoides, and P. uechtritzii) depicted by comprehensive LC-MS and multivariate data analysis. Antioxidants, 11(9), 1712. https://doi.org/10.3390/antiox11091712
De Souza, L. G., Renn O B, M. N., & Figueroa-Villar, J. D. (2016). Cou- marins as cholinesterase inhibitors: A review. Chemico-Biological Interactions, 254, 11–23. https://doi.org/10.1016/j.cbi.2016.05.001
Doković, D. D., Bulatović, V. M., Božić, B. D., Kataranovski, M. V., Zrakić, 56 T. M., & Kovačević, N. N. (2004). 3,5-nonadiyne isolated from the rhi- zome of Cachrys ferulacea inhibits endogenous nitric oxide release by rat peritoneal macrophages. Chemical and Pharmaceutical Bul- letin, 52(7), 853–854. https://doi.org/10.1248/cpb.52.853
Duman, H., & Watson, M. F. (1999). Ekimia, a new genus of Umbel- liferae, and two new taxa of Prangos Lindl. (Umbelliferae) from southern Turkey. Edinburgh Journal of Botany, 56(2), 199–209. https://doi.org/10.1017/s0960428600001086
Ellman, G. L., Courtney, K. D., Andres, V., & Featherstone, R. M. (1961). A new and rapid colorimetric determination of acetyl- cholinesterase activity. Biochemical Pharmacology, 7(2), 88–95. https://doi.org/10.1016/0006-2952(61)90145-9
Erdogan Orhan, I., Orhan, G., & Gurkas, E. (2011). An overview on natural cholinesterase inhibitors - a multi-targeted drug class - and their mass production. Mini-Reviews in Medicinal Chemistry, 11(10), 836–842. https://doi.org/10.2174/138955711796575434
Fais, A., Corda, M., Era, B., Fadda, M. B., Matos, M. J., Santana, L., … Delogu, G. (2009). Tyrosinase inhibitor activity of coumarin- resveratrol hybrids. Molecules, 14(7), 2514–2520.
Farkhad, N. K., Farokhi, F., & Tukmacki, A. (2012). Hydro-alcoholic extract of the root of Prangos ferulacea (L.) Lindl can improve se- rum glucose and lipids in alloxan-induced diabetic rats. Avicenna Journal of Phytomedicine, 2(4), 179.
Farokhi, F., Farkhad, N. K., & Togmechi, A. (2012). Preventive effects of Prangos ferulacea (L.) Lindle on liver damage of diabetic rats in- duced by alloxan. Avicenna Journal of Phytomedicine, 2(2), 63–71.
Farooq, S., Dangroo, N. A., Priya, D., Banday, J. A., Sangwan, P. L., Qurishi, M. A., … Saxena, A. K. (2014). Isolation, cytotoxicity evalu- ation and HPLC-quantification of the chemical constituents from Prangos pabularia. PloS One, 9(10), e108713. https://doi. org/10.1371/journal.pone.0108713
Granica, S., Kiss, A. K., Jarończyk, M., Maurin, J. K., Mazurek, A. P., & Czarnocki, Z. (2013). Synthesis of imperatorin analogs and their evaluation as acetylcholinesterase and butyrylcholinesterase inhibitors. Archiv Der Pharmazie, 346(11), 775–782. https://doi. org/10.1002/ardp.201300259
Greig, N. H., Lahiri, D. K., & Sambamurti, K. (2002). Butyrylcholines- terase: An important new target in Alzheimer’s disease therapy. International Psychogeriatrics, 14(SUPPL. 1), 77–91. https://doi. org/10.1017/S1041610203008676
Greig, N. H., Utsuki, T., Yu, Q., Zhu, X., Holloway, H. W., Perry, T.,… Lahiri, D. K. (2001). A new therapeutic target in Alzheimer’s disease treatment: Attention to butyrylcholinesterase. Cur- rent Medical Research and Opinion, 17(3), 159–165. https://doi. org/10.1185/0300799039117057
Karahisar, E., Köse, Y. B., İşcan, G., Kürkçüoğlu, M., & Tugay, O. (2022). Chemical composition and anticandidal activity of essential oils obtained from different parts of Prangos heyniae H. Duman & M.
F. Watson. Records of Natural Products, 16(1), 84–91. https://doi. org/10.25135/rnp.256.21.03.2017
Karakaya, S., Bingol, Z., Koca, M., Dagoglu, S., Pınar, N. M., Demirci, B., … Sytar, O. (2020). Identification of non-alkaloid natural com- pounds of Angelica purpurascens (Avé-Lall.) Gilli. (Apiaceae) with cholinesterase and carbonic anhydrase inhibition potential. Saudi Pharmaceutical Journal, 28(1), 1–14. https://doi.org/10.1016/j. jsps.2019.11.001
Kogure, K., Yamauchi, I., Tokumura, A., Kondou, K., Tanaka, N., Takaishi, Y., & Fukuzawa, K. (2004). Novel antioxidants isolated from plants of the genera Ferula, Inula, Prangos and Rheum col- lected in Uzbekistan. Phytomedicine, 11(7–8), 645–651. https:// doi.org/10.1016/j.phymed.2003.09.004
Koyu, H., Kazan, A., Demir, S., Haznedaroglu, M. Z., & Yesil-Celiktas, O. (2018). Optimization of microwave assisted extraction of Morus nigra L. fruits maximizing tyrosinase inhibitory activity with iso- lation of bioactive constituents. Food Chemistry, 248, 183–191. https://doi.org/10.1016/J.FOODCHEM.2017.12.049
Lyskov, D. F., Degtjareva, G. V., Samigullin, T. H., & Pimenov, M. G. (2017). The revision of Prangos subsections Koelzella and Fedtschenkoana (Apiaceae) with some notes to phylogeny and biogeography of the genus: Molecular and morphological evi- dences. Plant Systematics and Evolution, 303(7), 815–826. https:// doi.org/10.1007/s00606-017-1412-0
Massumi, M. A., Fazeli, M. R., Alavi, S. H. R., & Ajani, Y. (2007). Chemi- cal constituents and antibacterial activity of essential oil of Pran- gos ferulacea (L.) Lindl. fruits. Iranian Journal of Pharmaceutical Sciences, 3(3), 171–176.
Menemen, Y. (2012). Türkiye bitkileri listesi:(damarlı bitkiler) (1st ed.; A. Guner, ed.). İstanbul: Nezahat Gökyiğit Botanik Bahçesi Yayınları.
Mottaghipisheh, J., Kiss, T., Tóth, B., & Csupor, D. (2020). The Prangos genus: A comprehensive review on traditional use, phytochem- istry, and pharmacological activities. Phytochemistry Reviews, 19, 1449–1470. https://doi.org/10.1007/s11101-020-09688-3
Öke-Altuntaş, F., Aslım, B., Duman, H., Gülpınar, A. R., & Kartal, M. (2015). The relative contributions of chlorogenic acid and rutin to antioxidant activities of two endemic Prangos (Umbelliferae) species (P.heynia and P.denticulata). Journal of Food Biochemistry, 39(4), 409–416. https://doi.org/10.1111/jfbc.12137
Orhan, I. E., Tosun, F., Senol Deniz, F. S., Eren, G., Mıhoğlugil, F., Akal- gan, D., & Miski, M. (2021). Butyrylcholinesterase-inhibiting natu- ral coumarin molecules as potential leads. Phytochemistry Letters, 44, 48–54. https://doi.org/10.1016/J.PHYTOL.2021.05.001
Özbek, H., Güvenalp, Z., Yılmaz, G., Yerdelen, K., Kazaz, C., & Demirezer, Ö. L. (2018). In vitro anticholinesterase activity and molecular docking studies of coumarin derivatives isolated from roots of Heptaptera cilicica. Medicinal Chemistry Research, 27(2), 538–545. https://doi.org/10.1007/s00044-017-2080-x
Özek, G., Bedir, E., Tabanca, N., Ali, A., Khan, I. A., Duran, A., … Özek, T. (2018). Isolation of eudesmane type sesquiterpene ketone from Prangos heyniae H.Duman & M.F.Watson essential oil and mosquitocidal activity of the essential oils. Open Chemistry, 1(2), 122–135. https://doi.org/10.1515/chem-2018-0051
Özek, G., Özek, T., Işcan, G., Başer, K. H. C., Hamzaoglu, E., & Duran, A. (2007). Comparison of hydrodistillation and microdistillation methods for the analysis of fruit volatiles of Prangos pabularia Lindl., and evaluation of its antimicrobial activity. South African Journal of Botany, 73(4), 563–569. https://doi.org/10.1016/j.sajb.2007.05.002
Palmioli, A., Bertuzzi, S., De Luigi, A., Colombo, L., La Ferla, B., Salmona, M., … Airoldi, C. (2019). bioNMR-based identifica- tion of natural anti-Aβ compounds in Peucedanum ostruthium. Bioorganic Chemistry, 83, 76–86. https://doi.org/10.1016/J. BIOORG.2018.10.016
Sevin, G., Alan, E., Demir, S., Albayrak, G., Demiroz, T., Yetik-Ana- cak, G., & Baykan, S. (2022). Comparative evaluation of relaxant effects of three prangos species on mouse corpus cavernosum: Chemical characterization and the relaxant mechanisms of ac- tion of P. pabularia and (+)-oxypeucedanin. Journal of Ethnophar- macology, 284(March 2021), 114823. https://doi.org/10.1016/j. jep.2021.114823
Shokoohinia, Y., Sajjadi, S. E., Gholamzadeh, S., Fattahi, A., & Beh- bahani, M. (2014). Antiviral and cytotoxic evaluation of coumarins from Prangos ferulacea. Pharmaceutical Biology, 52(12), 1543– 1549. https://doi.org/10.3109/13880209.2014.907322
Shu, P., Li, J., Fei, Y., Zhu, H., Yu, M., Liu, A., … Xu, Z. (2020). Isolation, structure elucidation, tyrosinase inhibitory, and antioxidant evaluation of the constituents from Angelica dahurica roots. Jour- nal of Natural Medicines, 74(2), 456–462. https://doi.org/10.1007/ s11418-019-01375-8
So, Y. K., & Young, C. K. (2007). Neuroprotective coumarins from the root of Angelica gigas: Structure-activity relationships. Ar- chives of Pharmacal Research, 30(11), 1368–1373. https://doi. org/10.1007/bf02977358
Tada, Y., Shikishima, Y., Takaishi, Y., Shibata, H., Higuti, T., Honda, G., … Ashurmetov, O. (2002). Coumarins and γ-pyrone deriva- tives from Prangos pabularia: Antibacterial activity and inhibition of cytokine release. Phytochemistry, 59(6), 649–654. https://doi. org/10.1016/S0031-9422(02)00023-7
Ulubelen, A., Topcu, G., Tan, N., Ölçal, S., Johansson, C., Üçer, M., … Tamer, Ş. (1995). Biological activities of a Turkish medicinal plant, Prangos platychlaena. Journal of Ethnopharmacology, 45(3), 193–197. https://doi.org/10.1016/0378-8741(94)01215-L
Walsh, R., Rockwood, K., Martin, E., & Darvesh, S. (2011). Syner- gistic inhibition of butyrylcholinesterase by galantamine and citalopram. Biochimica et Biophysica Acta - General Subjects, 1810, 1230–1235. https://doi.org/10.1016/j.bbagen.2011.08.010
Wszelaki, N., Paradowska, K., Jamróz, M. K., Granica, S., & Kiss, A. K. (2011). Bioactivity-guided fractionation for the butyrylcholin- esterase inhibitory activity of furanocoumarins from Angelica archangelica L. roots and fruits. Journal of Agricultural and Food Chemistry, 59(17), 9186–9193. https://doi.org/10.1021/jf201971s
Youkwan, J., Sutthivaiyakit, S., & Sutthivaiyakit, P. (2010). Citruso- sides A-D and furanocoumarins with cholinesterase inhibitory activity from the fruit peels of Citrus hystrix. Journal of Natural Products, 73(11), 1879–1883. https://doi.org/10.1021/np100531x
Zahri, S., Razavi, S. M., Niri, F. H., & Mohammadi, S. (2009). Induc- tion of programmed cell death by Prangos uloptera, a medicinal plant. Biological Research, 42(4), 517–522. https://doi.org/10.4067/ S0716-97602009000400013
Zengin, G., Mahomoodally, M. F., Yıldıztugay, E., Jugreet, S., Khan, S. U., Dall’Acqua, S., … Montesano, D. (2022). Chemical compo- sition, biological activities and in silico analysis of essential oils of three endemic Prangos species from Turkey. Molecules 2022, Vol. 27, Page 1676, 27(5), 1676. https://doi.org/10.3390/MOL- ECULES27051676
Zengin, G., Sinan, K. I., Ak, G., Mahomoodally, M. F., Paksoy, M. Y., Picot-Allain, C., … Custodio, L. (2020). Chemical profile, antioxi- dant, antimicrobial, enzyme inhibitory, and cytotoxicity of seven Apiaceae species from Turkey: A comparative study. Industrial Crops and Products, 153, 112572. https://doi.org/10.1016/j.ind- crop.2020.112572
Zolghadri, S., Bahrami, A., Hassan Khan, M. T., Munoz-Munoz, J., Garcia-Molina, F., Garcia-Canovas, F., & Saboury, A. A. (2019). A comprehensive review on tyrosinase inhibitors. Journal of Enzyme Inhibition and Medicinal Chemistry, 34(1), 279–309. https://doi.org/10.1080/14756366.2018.1545767