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Biochemical constituent, enzyme inhibitory activity, and molecular docking analysis of an endemic plant species, Thymus migricus

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Abstract

Medicinal plants have been used traditionally since ancient times as alternative medications to treat various human diseases. In this work, we examined the chemical constituent, antioxidant activity, and enzyme inhibition of an endemic plant Thymus migricus. The plant extracts showed remarkable inhibition effects against the acetylcholinesterase (AChE), butyrylcholinesterase (BChE), glutathione S-transferase (GST), and α-glycosidase (α-Gly) enzymes that are linked with some metabolic disorders. IC50 values (concentration of a sample to inhibit 50% of enzyme activity) for AChE, BChE, GST, and α-Gly were found as 18.23 mg/mL, 17.77 mg/mL, 31.5 mg/ml, and 16.5 mg/mL, respectively. Antioxidant activities of water extract of T. migricus (WET) and methanol extract of T. migricus (MET) were determined using four in vitro techniques. The extracts showed considerable antioxidant actions on all four techniques. In addition, quinic acid (18.30 mg/g), chlorogenic acid (0.94 mg/g), cynaroside (0.49 mg/g), luteolin (0.21 mg/g), and p-coumaric acid (0.19 mg/g) were characterized as major phenolic compounds using advanced LC–MS/MS technique. The interactions of some phenolic compounds with the enzymes have been investigated using molecular docking studies. The docking analysis results revealed that the interactions of the major compounds of the plant with AChE, BChE, GST, and α-Gly enzymes are responsible for the inhibitory activity.

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References

  • Alisi IO, Uzairu A, Abechi SE, Idris SO (2018) Evaluation of the antioxidant properties of curcumin derivatives by genetic function algorithm. J Adv Res 12:47–54

    CAS  PubMed  PubMed Central  Google Scholar 

  • Aouam I, Atki YE, Taleb M, Taroq A, Kamari FE, Lyoussi B, Abdellaoui A (2019) Antioxidant capacities and total phenolic contents of Thymus riatarum. Mater Today Proc 13:579–586

    CAS  Google Scholar 

  • Apak R, Güçlü K, Özyürek M, Esin Karademir S, Erçağ E (2006) The cupric ion reducing antioxidant capacity and polyphenolic content of some herbal teas. Int J Food Sci Nutr 57:292–304

    CAS  PubMed  Google Scholar 

  • Aras A, Silinsin M, Bingol MN, Bursal E (2017) Identification of bioactive polyphenolic compounds and assessment of antioxidant activity of Origanum acutidens. ILNS 66:1–8

    Google Scholar 

  • Aras A, Bursal E, Alan Y, Türkan F, Alkan H, Kılıç Ö (2018) polyphenolic content, antioxidant potential and antimicrobial activity of Satureja boissieri. Iran J Chem Chem Eng Res 37:209–219

    CAS  Google Scholar 

  • Aras A, Bursal E, Türkan F, Tohma H, Kılıç Ö, Gülçin İ, Köksal E (2019) Phytochemical content, antidiabetic, anticholinergic, and antioxidant activities of endemic Lecokia cretica extracts. Chem Biodiv 16:e1900341

    CAS  Google Scholar 

  • Aslan HE, Demir Y, Özaslan MS, Türkan F, Beydemir Ş, Küfrevioğlu ÖI (2018) The behavior of some chalcones on acetylcholinesterase and carbonic anhydrase activity. Drug Chem Toxicol 42:1–7

    Google Scholar 

  • Baharfar R, Azimi R, Mohseni M (2015) Antioxidant and antibacterial activity of flavonoid-, polyphenol-and anthocyanin-rich extracts from Thymus kotschyanus boiss & hohen aerial parts. J Food Sci Technol 52:6777–6783

    CAS  PubMed  PubMed Central  Google Scholar 

  • Başer KHC, Demirci B, Ne K, Satil F, Tümen G (2002) The essential oils of Thymus migricus and T. fedtschenkoi var. handelii from Turkey. Flavour Fragrance J 17:41–45

    Google Scholar 

  • Burley SK et al (2019) RCSB Protein Data Bank: biological macromolecular structures enabling research and education in fundamental biology, biomedicine, biotechnology and energy. Nucleic acids Res 47:D464–D474

    CAS  PubMed  Google Scholar 

  • Burmaoglu S, Yilmaz AO, Polat MF, Kaya R, Gulcin İ, Algul O (2019) Synthesis and biological evaluation of novel tris-chalcones as potent carbonic anhydrase, acetylcholinesterase, butyrylcholinesterase and α-glycosidase inhibitors. Bioorg Chem 85:191–197

    CAS  PubMed  Google Scholar 

  • Bursal E, Aras A, Kılıç Ö (2019a) Evaluation of antioxidant capacity of endemic plant Marrubium astracanicum subsp. macrodon: ıdentification of its phenolic contents by using HPLC-MS/MS. Nat Prod Res 33:1975–1979

    CAS  PubMed  Google Scholar 

  • Bursal E, Aras A, Kılıç Ö, Taslimi P, Gören AC, Gülçin İ (2019b) Phytochemical content, antioxidant activity, and enzyme inhibition effect of Salvia eriophora Boiss. & Kotschy against acetylcholinesterase, α-amylase, butyrylcholinesterase, and α-glycosidase enzymes. J Food Biochem 43:e12776

    PubMed  Google Scholar 

  • Bursal E, Taslimi P, Gören AC, Gülçin İ (2020) Assessments of anticholinergic, antidiabetic, antioxidant activities and phenolic content of Stachys annua. Biocatal Agric Biotechnol 28:101711

    Google Scholar 

  • Chen Y et al (2017) Discovery of new acetylcholinesterase and butyrylcholinesterase inhibitors through structure-based virtual screening. RSC Adv 7:3429–3438

    CAS  Google Scholar 

  • Cheng Z-Q et al (2019) Molecular-docking-guided design and synthesis of new IAA-tacrine hybrids as multifunctional AChE/BChE inhibitors. Bioorg Chem 83:277–288

    CAS  PubMed  Google Scholar 

  • Dob T, Dahmane D, Benabdelkader T, Chelghoum C (2006) Studies on the essential oil composition and antimicrobial activity of Thymus algeriensis Boiss. et Reut. Int J Aromather 16:95–100

    CAS  Google Scholar 

  • Gonçalves M, Cruz M, Cavaleiro C, Lopes M, Salgueiro L (2010) Chemical, antifungal and cytotoxic evaluation of the essential oil of Thymus zygis subsp. sylvestris. Ind Crops Prod 32:70–75

    Google Scholar 

  • Govindharaj D, Nachimuthu S, Gonsalves DF, Kothandan R, Dhurai B, Rajamani L, Ramakrishana S (2020) Molecular docking analysis of chlorogenic acid against matrix metalloproteinases (MMPs). Biointerface Ress Appl 10:6865–6873

    CAS  Google Scholar 

  • Gülçin İ, Scozzafava A, Supuran CT, Akıncıoğlu H, Koksal Z, Turkan F, Alwasel S (2016) The effect of caffeic acid phenethyl ester (CAPE) on metabolic enzymes including acetylcholinesterase, butyrylcholinesterase, glutathione S-transferase, lactoperoxidase, and carbonic anhydrase isoenzymes I II, IX, and XII. J Enzyme Inhib Med Chem 31:1095–1101

    PubMed  Google Scholar 

  • Gülçin İ et al (2016) Rosmarinic acid inhibits some metabolic enzymes including glutathione S-transferase, lactoperoxidase, acetylcholinesterase, butyrylcholinesterase and carbonic anhydrase isoenzymes. J Enzyme Inhib Med Chem 31:1698–1702

    PubMed  Google Scholar 

  • Gülçin İ, Gören AC, Taslimi P, Alwasel SH, Kılıc O, Bursal E (2020) Anticholinergic, antidiabetic and antioxidant activities of Anatolian pennyroyal (Mentha pulegium)-analysis of its polyphenol contents by LC-MS/MS. Biocatal Agric Biotechnol 23:101441

    Google Scholar 

  • Gulçin İ et al (2018) Antidiabetic and antiparasitic potentials: ınhibition effects of some natural antioxidant compounds on α-glycosidase, α-amylase and human glutathione S-transferase enzymes. Int J Biol Macromol 119:741–746

    PubMed  Google Scholar 

  • Gulcin İ (2020) Antioxidants and antioxidant methods: an updated overview. Arch Toxicol 94:651–715

    CAS  PubMed  Google Scholar 

  • Hassan W et al (2017) Oxidative stress and antioxidant potential of one hundred medicinal plants. Curr Top Med Chem 17:1336–1370

    CAS  PubMed  Google Scholar 

  • Hazzit M, Baaliouamer A, Veríssimo A, Faleiro M, Miguel MG (2009) Chemical composition and biological activities of Algerian Thymus oils. Food Chem 116:714–721

    CAS  Google Scholar 

  • Işık M, Beydemir Ş (2020) The impact of some phenolic compounds on serum acetylcholinesterase: kinetic analysis of an enzyme/inhibitor interaction and molecular docking study. J Biomol Struct Dyn. https://doi.org/10.1080/07391102.2020.1801509

    Article  PubMed  Google Scholar 

  • Işık M, Demir Y, Durgun M, Türkeş C, Necip A, Beydemir Ş (2019) Molecular docking and investigation of 4-(benzylideneamino)-and 4-(benzylamino)-benzenesulfonamide derivatives as potent AChE inhibitors. Chem Papers 1–11

  • Karimov A et al (2020) Novel functionally substituted esters based on sodium diethyldithiocarbamate derivatives: Synthesis, characterization, biological activity and molecular docking studies. Bioorg Chem 99:103762

    CAS  PubMed  Google Scholar 

  • Kocyigit UM et al (2018) 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

    CAS  PubMed  Google Scholar 

  • Koeduka T et al (2014) Bioactivity of natural O-prenylated phenylpropenes from I llicium anisatum leaves and their derivatives against spider mites and fungal pathogens. Plant Biol 16:451–456

    CAS  PubMed  Google Scholar 

  • Köksal E, Bursal E, Gülçin İ, Korkmaz M, Çağlayan C, Gören AC, Alwasel SH (2017) Antioxidant activity and polyphenol content of Turkish thyme (Thymus vulgaris) monitored by liquid chromatography and tandem mass spectrometry. Int J Food Prop 20:514–525

    Google Scholar 

  • Küçükbay FZ, Kuyumcu E, Azaz AD, Arabacı T, Yücetürk SÇ (2014) Chemical composition of the essential oils of three Thymus taxa from Turkey with antimicrobial and antioxidant activities. Rec Nat Prod 2:110–120

    Google Scholar 

  • Lipinski CA, Lombardo F, Dominy BW, Feeney PJ (1997) Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev 23:3–25

    CAS  Google Scholar 

  • Lu X et al (2019) Expansion of the scaffold diversity for the development of highly selective butyrylcholinesterase (BChE) inhibitors: discovery of new hits through the pharmacophore model generation, virtual screening and molecular dynamics simulation. Bioorg Chem 85:117–127

    CAS  PubMed  Google Scholar 

  • Nirmala C, Bisht MS, Bajwa HK, Santosh O (2018) Bamboo: a rich source of natural antioxidants and its applications in the food and pharmaceutical industry. Trends Food Sci Technol 77:91–99

    CAS  Google Scholar 

  • Release S (2019) 3: Maestro Schrödinger. LLC, New York, p 2019

    Google Scholar 

  • Rendra E, Riabov V, Mossel DM, Sevastyanova T, Harmsen MC, Kzhyshkowska J (2019) Reactive oxygen species (ROS) in macrophage activation and function in diabetes. Immunobiology 224:242–253

    CAS  PubMed  Google Scholar 

  • Rota MC, Herrera A, Martínez RM, Sotomayor JA, Jordán MJ (2008) Antimicrobial activity and chemical composition of Thymus vulgarisThymus zygis and Thymus hyemalis essential oils. Food Control 19:681–687

    CAS  Google Scholar 

  • Silinsin M, Bursal E (2018) UHPLC-MS/MS phenolic profiling and in vitro antioxidant activities of Inula graveolens (L.) Desf. Nat Prod Res 32:1467–1471

    CAS  PubMed  Google Scholar 

  • Tao Y, Zhang Y, Cheng Y, Wang Y (2013) Rapid screening and identification of α-glucosidase inhibitors from mulberry leaves using enzyme-immobilized magnetic beads coupled with HPLC/MS and NMR. Biomed Chromatogr 27:148–155

    CAS  PubMed  Google Scholar 

  • Taslimi P et al (2020) Anti-Alzheimer, antidiabetic and antioxidant potential of Satureja cuneifolia and analysis of its phenolic contents by LC-MS/MS. Arab J Chem 13:4528–4537

    CAS  Google Scholar 

  • Taslimi P, Turhan K, Türkan F, Karaman HS, Turgut Z, Gulcin I (2020) Cholinesterases, α-glycosidase, and carbonic anhydrase inhibition properties of 1H-pyrazolo [1, 2-b] phthalazine-5, 10-dione derivatives: synthetic analogues for the treatment of Alzheimer's disease and diabetes mellitus. Bioorg Chem 97:103647

    CAS  PubMed  Google Scholar 

  • Tohidi B, Rahimmalek M, Arzani A (2017) Essential oil composition, total phenolic, flavonoid contents, and antioxidant activity of Thymus species collected from different regions of Iran. Food Chem 220:153–161

    CAS  PubMed  Google Scholar 

  • Türkan F, Huyut Z, Taslimi P, Gülçin İ (2019) The effects of some antibiotics from cephalosporin groups on the acetylcholinesterase and butyrylcholinesterase enzymes activities in different tissues of rats. Arch Physiol Biochem 125:12–18

    PubMed  Google Scholar 

  • Turrens JF (2003) Mitochondrial formation of reactive oxygen species. J Physiol 552:335–344

    CAS  PubMed  PubMed Central  Google Scholar 

  • Uysal S et al (2018) Novel in vitro and in silico insights of the multi-biological activities and chemical composition of Bidens tripartita L. Food Chem Toxicol 111:525–536

    CAS  PubMed  Google Scholar 

  • Varela MT, Ferrarini M, Mercaldi VG, da Silva SB, Padovani G, Nazato LIS, Fernandes JPS (2020) Coumaric acid derivatives as tyrosinase inhibitors: efficacy studies through in silico, in vitro and ex vivo approaches. Bioorg Chem 103:104108–104108

    CAS  PubMed  Google Scholar 

  • Visualizer DS (2005) Accelrys software inc Discovery Studio Visualizer 2

  • Yates K, Pohl F, Busch M, Mozer A, Watters L, Shiryaev A, Lin PKT (2019) Determination of sinapine in rapeseed pomace extract: its antioxidant and acetylcholinesterase inhibition properties. Food Chem 276:768–775

    CAS  PubMed  Google Scholar 

  • Yener I et al (2020) Selective in vitro and in silico enzymes ınhibitory activities of phenolic acids and flavonoids of food plants: relations with oxidative stress. Food Chem 327:127045

    CAS  PubMed  Google Scholar 

  • Yilmaz MA (2020) Simultaneous quantitative screening of 53 phytochemicals in 33 species of medicinal and aromatic plants: a detailed, robust and comprehensive LC–MS/MS method validation. Ind Crops Prod 149:112347

    CAS  Google Scholar 

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Acknowledgements

This study was carried out in Iğdır University Research Laboratory Application and Research Center (ALUM).

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Authors and Affiliations

  1. Department of Biochemistry, Faculty of Science and Arts, Iğdır University, Iğdır, Turkey

    Abdülmelik Aras & Mehmet Nuri Atalar

  2. Health Services Vocational School, Iğdır University, Iğdır, Turkey

    Fikret Türkan

  3. Department of Bioengineering, Architecture and Engineering Faculty, Kafkas University, Kars, Turkey

    Umit Yildiko

  4. Department of Pharmaceutical Sciences, Pharmacy Faculty, Adıyaman University, Adıyaman, Turkey

    Ömer Kılıç

  5. Department of Environmental Engineering, Faculty of Engineering, Iğdır University, Iğdır, Turkey

    Mehmet Hakki Alma

  6. Department of Nursing, Faculty of Health, Muş Alparslan University, Muş, Turkey

    Ercan Bursal

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Aras, A., Türkan, F., Yildiko, U. et al. Biochemical constituent, enzyme inhibitory activity, and molecular docking analysis of an endemic plant species, Thymus migricus. Chem. Pap. 75, 1133–1146 (2021). https://doi.org/10.1007/s11696-020-01375-z

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