Antioxidant, anti-acetylcholinesterase potentials, ADME estimations and molecular docking studies of green algae extracts

Year 2025, , 24 - 35, 30.04.2025

Olgun Çirak , Adem Necip , Mesut Isık , Şükrü Beydemir

https://doi.org/10.55971/EJLS.1648632

Abstract

Algae have become the center of attention due to their strong antioxidants and enzyme-inhibitory activities. In this study, green algae (Enteromorpha linza) extracts obtained using acetone, hexane and methanol were investigated. In the study, antioxidant properties, anti-acetylcholinesterase (AChE) potential, ADME estimations and molecular docking analyses of green algae extracts were investigated. The best binding position was obtained by docking sirsimaritin, daidzein, kaempferol, morin and myricetin to the active site of acetylcholinesterase receptor. Docking score values were calculated as -10.0, -10.3, -9.9, -9.8 and -9.8 kcal/mol, respectively. Experimental analysis revealed that the extracts showed inhibitory activity against acetylcholinesterase enzyme. Acetone and hexane extract showed good inhibition performance with IC50 values of 0.0379 mg/ml and 0.0414 mg/ml, respectively. The IC50 value for methanol extract was determined as 0.997 mg/ml. When the antioxidant activity results of the extracts were evaluated in terms of both DPPH and ABTS radical scavenging capacities, it was revealed that the acetone-based extract had a higher radical scavenging capacity (DPPH: 17.48%, ABTS: 83.58%) compared to the extracts obtained with other solvents. In general, the obtained results revealed that the green algae examined can be used as a source of natural agents beneficial for human health.

Keywords

AChE, Algae, Antioxidant, Inhibition, Molecular docking

References

• Wijesekara I, Pangestuti R, Kim S-K. Biological activities and potential health benefits of sulfated polysaccharides derived from marine algae. Carbohydr. Polym. (2011);84(1):14–21. https://doi.org/10.1016/j.carbpol.2010.10.062
• Ibrahim M, Salman M, Kamal S, Rehman S, Razzaq A, Akash SH. Algae-Based Biologically Active Compounds. Algae Based Polym. Blends Compos., Elsevier: (2017):155–271. https://doi.org/10.1016/B978-0-12-812360-7.00006-9
• Yu Y, Li Y, Du C, Mou H, Wang P. Compositional and structural characteristics of sulfated polysaccharide from Enteromorpha prolifera. Carbohydr. Polym. (2017);165:221–228. https://doi.org/10.1016/j.carbpol.2017.02.011
• Eismann AI, Perpetuo Reis R, Ferreira Da Silva A, Negrão Cavalcanti D. Ulva spp. carotenoids: Responses to environmental conditions. Algal Res. (2020);48:101916. https://doi.org/10.1016/j.algal.2020.101916
• Liang Y, Yu W, Wang H, Yao L, He Z, Sun M, Feng T, Yu C, Yue H. Flash extraction of ulvan polysaccharides from marine green macroalga Ulva linza and evaluation of its antioxidant and gut microbiota modulation activities. Int. J. Biol. Macromol. (2024);262:130174. https://doi.org/10.1016/j.ijbiomac.2024.130174
• Ning L, Yao Z, Zhu B. Ulva (Enteromorpha) Polysaccharides and Oligosaccharides: A Potential Functional Food Source from Green-Tide-Forming Macroalgae. Mar. Drugs (2022);20(3):202. https://doi.org/10.3390/md20030202
• Zhong R, Wan X, Wang D, Zhao C, Liu D, Gao L, Wang M, Wu C, Nabavid SM, Daglia M, Capanoglu E, Xiao J, Cao H. Polysaccharides from Marine Enteromorpha: Structure and function. Trends Food Sci. Technol. (2020);99:11–20. https://doi.org/10.1016/j.tifs.2020.02.030
• Pari RF, Uju U, Hardiningtyas SD, Ramadhan W, Wakabayashi R, Goto M, Kamiya N. Ulva Seaweed-Derived Ulvan: A Promising Marine Polysaccharide as a Sustainable Resource for Biomaterial Design. Mar. Drugs (2025);23(2):56. https://doi.org/10.3390/md23020056
• Günsel A, Günsel H, Taslimi P, Taskin-Tok T, Erden BA, Bilgiçli AT, Sadeghian N, Gülçin İ, Yarasir MN. Novel composite structures based on cobalt phthalocyanine/graphene oxide: Identification of potential drug candidates to treat Alzheimer’s disease and diabetes. Inorganica Chim. Acta (2024);570:122190. https://doi.org/10.1016/j.ica.2024.122190
• Topal F, Gulcin I, Dastan A, Guney M. Novel eugenol derivatives: Potent acetylcholinesterase and carbonic anhydrase inhibitors. Int. J. Biol. Macromol. (2017);94:845–851. https://doi.org/10.1016/j.ijbiomac.2016.10.096
• Zhai J, Hao C, Wang X, Cao Y, Pan Y, Zhou M, Sun J, Li C. Design, synthesis, and evaluation of dual‐target inhibitors for the treatment of Alzheimer’s disease. Arch. Pharm. (Weinheim) (2024);357(5):2300693. https://doi.org/10.1002/ardp.202300693
• Genc Bilgicli H, Ergon D, Taslimi P, Tüzün B, Akyazı Kuru İ, Zengin M, Gülçin İ. Novel propanolamine derivatives attached to 2-metoxifenol moiety: Synthesis, characterization, biological properties, and molecular docking studies. Bioorganic Chem. (2020);101:103969. https://doi.org/10.1016/j.bioorg.2020.103969
• Özbey F, Taslimi P, Gülçin İ, Maraş A, Göksu S, Supuran CT. Synthesis of diaryl ethers with acetylcholinesterase, butyrylcholinesterase and carbonic anhydrase inhibitory actions. J. Enzyme Inhib. Med. Chem. (2016);31(sup2):79–85. https://doi.org/10.1080/14756366.2016.1189422
• Karlsson D, Fallarero A, Brunhofer G, Mayer C, Prakash O, Mohan CG, Vuorela P, Erker T. The exploration of thienothiazines as selective butyrylcholinesterase inhibitors. Eur. J. Pharm. Sci. (2012);47(1):190–205. https://doi.org/10.1016/j.ejps.2012.05.014
• Cetin Cakmak K, Gülçin İ. Anticholinergic and antioxidant activities of usnic acid-an activity-structure insight. Toxicol. Rep. (2019);6:1273–1280. https://doi.org/10.1016/j.toxrep.2019.11.003
• Noreen S, Sumrra SH, Chohan ZH, Mustafa G, Imran M. Synthesis, characterization, molecular docking and network pharmacology of bioactive metallic sulfonamide-isatin ligands against promising drug targets. J. Mol. Struct. (2023);1277:134780. https://doi.org/10.1016/j.molstruc.2022.134780
• Noreen S, Sumrra SH. Correlating the charge transfer efficiency of metallic sulfa-isatins to design efficient NLO materials with better drug designs. BioMetals (2022);35(3):519–548. https://doi.org/10.1007/s10534-022-00385-6
• Elmastaş M, Gülçin İ, Işildak Ö, Küfrevioğlu Öİ, İbaoğlu K, Aboul-Enein HY. Radical scavenging activity and antioxidant capacity of bay leaf extracts. J. Iran. Chem. Soc. (2006);3(3):258–266. https://doi.org/10.1007/BF03247217
• Gülçin İ, Elias R, Gepdiremen A, Boyer L. Antioxidant activity of lignans from fringe tree (Chionanthus virginicus L.). Eur. Food Res. Technol. (2006);223(6):759–767. https://doi.org/10.1007/s00217-006-0265-5
• Taslimi P, Gulçin İ. Antioxidant and anticholinergic properties of olivetol. J. Food Biochem. (2018);42(3):e12516. https://doi.org/10.1111/jfbc.12516
• Gülçin İ. Antioxidant properties of resveratrol: A structure–activity insight. Innov. Food Sci. Emerg. Technol. (2010);11(1):210–218. https://doi.org/10.1016/j.ifset.2009.07.002
• Gülçin İ. Antioxidant activity of food constituents: an overview. Arch. Toxicol. (2012);86(3):345–391. https://doi.org/10.1007/s00204-011-0774-2
• Gülçin İ. Antioxidant activity of l-adrenaline: A structure–activity insight. Chem. Biol. Interact. (2009);179(2–3):71–80. https://doi.org/10.1016/j.cbi.2008.09.023
• Gülçin İ, Elias R, Gepdiremen A, Taoubi K, Köksal E. Antioxidant secoiridoids from fringe tree (Chionanthus virginicus L.). Wood Sci. Technol. (2009);43(3–4):195–212. https://doi.org/10.1007/s00226-008-0234-1
• Bingol Z, Kızıltaş H, Gören AC, Kose LP, Topal M, Durmaz L, Alwasel SH, Gulcin İ. Antidiabetic, anticholinergic and antioxidant activities of aerial parts of shaggy bindweed (Convulvulus betonicifolia Miller subsp.) – profiling of phenolic compounds by LC-HRMS. Heliyon (2021);7(5):e06986. https://doi.org/10.1016/j.heliyon.2021.e06986
• Leyton A, Pezoa-Conte R, Barriga A, Buschmann AH, Mäki-Arvela P, Mikkola J-P, Lienqueo ME. Identification and efficient extraction method of phlorotannins from the brown seaweed Macrocystis pyrifera using an orthogonal experimental design. Algal Res. (2016);16:201–208. https://doi.org/10.1016/j.algal.2016.03.019
• Sinha SN, Paul D, Halder N, Sengupta D, Patra SK. Green synthesis of silver nanoparticles using fresh water green alga Pithophora oedogonia (Mont.) Wittrock and evaluation of their antibacterial activity. Appl. Nanosci. (2015);5(6):703–709. https://doi.org/10.1007/s13204-014-0366-6
• Eberhardt J, Santos-Martins D, Tillack AF, Forli S. AutoDock Vina 1.2.0: New Docking Methods, Expanded Force Field, and Python Bindings. J. Chem. Inf. Model. (2021);61(8):3891–3898. https://doi.org/10.1021/acs.jcim.1c00203
• Trott O, Olson AJ. AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J. Comput. Chem. (2010);31(2):455–461. https://doi.org/10.1002/jcc.21334
• Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC, Ferrin TE. UCSF Chimera—A visualization system for exploratory research and analysis. J. Comput. Chem. (2004);25(13):1605–1612. https://doi.org/10.1002/jcc.20084
• Gül Dikme T, Necip A, Dikme R, Güneş S. Effect of Phytosterols in Apricot Kernel on Cholesterol-Molecular Docking. (2024). https://doi.org/10.5281/ZENODO.13859625
• Necip A. KARDIYOVASKÜLER HASTALIKLARDA DOĞAL ÜRÜNLER: KURKUMİN VE QUERCETİN MOLEKÜLER DOCKİNG. (2024). https://doi.org/10.5281/ZENODO.10905644
• Diedrich K, Krause B, Berg O, Rarey M. PoseEdit: enhanced ligand binding mode communication by interactive 2D diagrams. J. Comput. Aided Mol. Des. (2023);37(10):491–503. https://doi.org/10.1007/s10822-023-00522-4
• Daina A, Michielin O, Zoete V. SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci. Rep. (2017);7(1):42717. https://doi.org/10.1038/srep42717
• Ellman GL, Courtney KD, Andres V, Featherstone RM. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem. Pharmacol. (1961);7(2):88–95. https://doi.org/10.1016/0006-2952(61)90145-9
• Swathi N, Kumar AG, Parthasarathy V, Sankarganesh P. Isolation of Enteromorpha species and analyzing its crude extract for the determination of in vitro antioxidant and antibacterial activities. Biomass Convers. Biorefinery (2024);14(3):3753–3762. https://doi.org/10.1007/s13399-022-02591-1
• Yildirim M, Dogan K, Necip A, Cimentepe M. Naringenin-loaded pHEMA cryogel membrane: preparation, characterization, antibacterial activity and in silico studies. Chem. Pap. (2025);79(1):211–220. https://doi.org/10.1007/s11696-024-03774-y
• Kaya B, Tahtacı H, Çiftçi B, Duran HE, Necip A, Işık M, Beydemir Ş. Discovery of Hydrazine Clubbed Thiazoles as Potential Antidiabetic Agents: Synthesis, Biological Evaluation, and Molecular Docking Studies. Drug Dev. Res. (2025);86(1):e70060. https://doi.org/10.1002/ddr.70060
• Leão C, Simões M, Borges A. Marine phenolics: Classes, antibacterial properties, and applications. Mar. Phenolic Compd., Elsevier: (2023):371–392. https://doi.org/10.1016/B978-0-12-823589-8.00013-3
• Ferdous UT, Balia Yusof ZN. Insight into Potential Anticancer Activity of Algal Flavonoids: Current Status and Challenges. Molecules (2021);26(22):6844. https://doi.org/10.3390/molecules26226844
• Peng Z, Wu Y, Fu Q, Xiao J. Free and bound phenolic profiles and antioxidant ability of eleven marine macroalgae from the South China Sea. Front. Nutr. (2024);11:1459757. https://doi.org/10.3389/fnut.2024.1459757
• Yildirim M, Yasar E, Necip A, Cimentepe M, Demirbağ B, Kilic A. Facile synthesis and spectral analysis of the bioactive spiroborate compounds as a novel therapeutic agent for computational insights, biological evaluation, and applications. J. Organomet. Chem. (2025);1027:123510. https://doi.org/10.1016/j.jorganchem.2025.123510
• Elamine Y, Anjos O, Estevinho LM, Lyoussi B, Aazza S, Miguel MG. Effect of extreme heat processing on the Moroccan Zantaz’ honey antioxidant activities. J. Food Sci. Technol. (2020);57(9):3323–3333. https://doi.org/10.1007/s13197-020-04365-x
• Khan MH, Dar NA, Alie BA, Dar SA, Lone AA, Mir GH, Fayaz U, Ali S, Tyagi A, El-Sheikh MA, Alansi S. Unraveling the Variability of Essential Oil Composition in Different Accessions of Bunium persicum Collected from Different Temperate Micro-Climates. Molecules (2023);28(5):2404. https://doi.org/10.3390/molecules28052404
• Lim S, Choi A-H, Kwon M, Joung E-J, Shin T, Lee S-G, Kim N-G, Kim H-R. Evaluation of antioxidant activities of various solvent extract from Sargassum serratifolium and its major antioxidant components. Food Chem. (2019);278:178–184. https://doi.org/10.1016/j.foodchem.2018.11.058