Selective in-vitro Enzymes’ Inhibitory Activities of Fingerprints Compounds of Salvia Species and Molecular Docking Simulations

Document Type : Research article

Authors

1 Department of Organic Chemistry, Faculty of Science, Dicle University, 21280 Diyarbakir, Turkey.

2 Dept of Pharmacognosy, Faculty of Pharmacy, Dicle University, 21280 Diyarbakir, Turkey.

3 Department of Analytical Chemistry, Faculty of Pharmacy, Dicle University, 21280 Diyarbakir, Turkey.

4 Department of Biochemistry, Faculty of Medicine, Girne American University, 99320 Girne, TRNC.

5 Department of Analytical Chemistry, Faculty of Pharmacy, Dicle University, TR-21280 Diyarbakir, Turkey.

6 The Council of Forensic Medicine, Ministry of Justice, Diyarbakir, 21100, Turkey.

7 Department of Chemistry, Faculty Science, Mugla Sıtkı Koçman University, TR-48121 Mugla, Turkey.

8 Department of Pharmacognosy and Phytochemistry, Bezmialem Vakif University, 34093 Istanbul, Turkey.

9 Department of General and Analytical Chemistry, Faculty of Pharmacy, Istanbul University, 34116 Istanbul, Turkey.

Abstract

Recently Nutrition and Food Chemistry researches have been focused on plants and their products or their secondary metabolites having anti-alzheimer, anti-cancer, anti-aging, and antioxidant properties. Among these plants Salvia L. (Lamiaceae) species come into prominence with their booster effects due to high antioxidant contents, which have over 900 species in the world and 98 in Turkey. Some Salvia species are already in use as herbal treatment of vessel stiffness, Dementia like problems and cancer. Recently some species of Salvia are of extensive research topic. In this study, inhibitory potentials of secondary metabolites, rosmarinic acid, salvigenin, salvianolic acid A and B, tanshinone I and IIA, cyrtotanshinone, dihydrotanshinone I, carnosic acid, carnosol, and danshensu sodium salt were investigated against acetylcholinesterase, butyrylcholinesterase, urease and tyrosinase enzymes both in vitro and in slico in detail. Elevated inhibitory effects on acetyl- and butyryl-cholinesterase of dihydrotanshinone I (IC50: 1.50±0.02 and 0.50±0.01 µg/mL, respectively), carnosol (IC50: 11.15±0.05 ve 3.92±0.03 µg/mL) and carnosic acid (IC50: 31.83±0.65 ve 4.12±0.04 µg/mL) were observed. Furthermore, all other secondary metabolites were active against butyrylcholinesterase. Anti-urease (42.41±0.85%) and anti-tyrosinase (39.82±1.16%) activities of tanshinone I were also observed. Potential inhibitory effects of these molecules on target proteins were investigated using DOCK and molecular dynamics calculations. Dock score analysis and Lipinski parameters were demonstrated that these ligands are potential inhibitors against relevant enzymes. Our findings suggest that Salvia species can be utilized as a potential source of anti-alzheimer active compounds for designing novel products

Graphical Abstract

Selective in-vitro Enzymes’ Inhibitory Activities of Fingerprints Compounds of Salvia Species and Molecular Docking Simulations

Keywords


(1) Howes MJR, Perry NSL and Houghton PJ. Plants with traditional uses and activities relevant to the management of Alzheimer’s disease and other cognitive disorders. Phytother Res. (2003) 17: 1-18.
(2) Witkop GJ. Inherited disordes of pigmentation. Clin Dermatol (1985) 3(1): 70 -134.
(3) Kalka K, Mukhtar H, Turowski-Wanke A and Merk H. Biomelanin antioxidants in cosmetics: assessment based on inhibition of lipid peroxidation. Skin Pharmacol Appl. (2000) 13: 143-149.
(4) Kikuchi K, Miura H, Yamamoto T, TakeuchiT, Dei T and Watanabe M. Characteristic sequences in the upstream region of the human tyrosinase gene. Biochimica et Biophysica Acta: Gene (1989) 1009(3): 283-286.
(5) Mantle D, Gok MA and Lennard TW. Adverse and beneficial effects of plant extracts on skin and skin disorders. Adverse Drug React Toxicol Rev. (2001) 20: 89-103.
(6) Mobley HLT and Hausinger RP. Microbial ureses: Significance, regulation, and molecular characterization. Microbiol Rev. (1989)  53: 85-108.
(7) Deveci E, Tel-Cayan G, Usluer O and Duru ME. Antioxidant, Anticholinesterase and Anti-Tyrosinase Activities of Essential Oils of Two Sideritis Species from Turkey. Iran J. Pharm. Res. (2019) 18(2): 903-913.
(8) Yener I, Ertas A, Yilmaz MA, Tokul Olmez O, Koseoglu Yilmaz P, Yesil Y, Kaplaner E, Ozturk M, Temel H, Kolak U and Topçu G. Characterization of the Chemical Profile of Euphorbia Species from Turkey by Gas Chromatography–Mass Spectrometry (GC-MS), Liquid Chromatography–Tandem Mass Spectrometry (LC-MS/MS), and Liquid Chromatography–Ion Trap–Time-of-Flight–Mass Spectrometry (LC-IT-TOF-MS) and Chemometric. Analysis Anal. Lett. (2018) 52(7): 1031-1049.
(9) Yener I, Tokul Olmez O, Ertas A, Yilmaz MA, Firat M, Irtegun Kandemir S, Ozturk M, Kolak U and Temel H. A detailed study on chemical and biological profile of nine Euphorbia species from Turkey with chemometric approach: Remarkable cytotoxicity of Euphorbia fistulasa and promising tannic acid content of Euphorbia eriophora. Ind. Crop Prod. (2018) 123: 442–453.
(10) Kurt BZ, Gazioglu I, Sevgi E and Sonmez F. Anticholinesterase, Antioxidant, Antiaflatoxigenic Activities of Ten Edible Wild Plants from Ordu Area, Turkey. Iran J. Pharm. Res. (2018) 17(3): 1047-1056.
(11) Topcu G and Goren AC. Biological Activity of Diterpenoids Isolated from Anatolian Lamiaceae Plants. Rec Nat Prod. (2007) 1(1): 1-16.
(12) Senol FS, Slusarczyk S, Matkowski A, Perez-Garrido A, Giron-Rodriguez F, Ceron-Carrasco JP, Haan Hden, Pena-Garcia J, Perez-Sanchez H, Domaradzki K and Erdogan-Orhan I. Selective in vitro and in silico butyrylcholinesterase inhibitory activity of diterpenes and rosmarinic acid isolated from Perovskia atriplicifolia Benth. and Salvia glutinosa L. Phytochemistry, (2017) 133: 33-44.
(13) Yasmin T, Tuhin MA, Haque S and Hossain M. Interaction of Quercetin of Onion with Axon Guidance Protein Receptor, NRP-1 Plays Important Role in Cancer Treatment: An In Silico Approach. Interdisciplinary Sciences: Computational Life Sciences (2017) 9/2:184-191.
(14) Rauf A, Erdogan Orhan I, Ertas A, Temel H, Hadda TB, Saleem M, Raza M and Khan H. Elucidation of Phosphodiesterase-1 Inhibitory Effect of Some Selected Natural Polyphenolics Using In Vitro and In Silico Methods. Curr. Top. Med. Chem. (2017) 17: 412-417.
(15) Ozbek H, Guvenalp Z, Yilmaz G, Yerdelen KO, Kazaz C and Demirezer OL. In vitro anticholinesterase activity and molecular docking studies of coumarin derivatives isolated from roots of Heptaptera cilicica. Med. Chem. Res. (2018) 27(2): 538-545.
(16) Karakaya S, Koca M, Kilic CS and Coskun M. Antioxidant and anticholinesterase activities of Ferulago syriaca Boiss. and F-isaurica Pesmen growing in Turkey. Med. Chem. Res. (2018) 27(7): 1843-1850.
(17) Orhan Erdogan I and Senol FS. Designing Multi-Targeted Therapeutics for the Treatment of Alzheimer's Disease. Curr. Top. Med. Chem. (2016) 16: 1889-1896.
(18) Dogan M, Kahraman A, Celep F and Karabacak E. Türkiye Bitkileri Listesi (Damarlı Bitkiler).Salvia L. İstanbul: Nezahat Gökyiğit Botanik Bahçesi ve Flora Araştırmaları Derneği Yayını, Pp. (2012) 575-582.
(19) Farimani MM, Miran M and Ebrahimi SN. Diterpenoids from the Aerial Parts of Salvia reuterana. Iran J. Pharm. Res.(2019) 18(1): 406-411.
(20) Baytop T. Tükçe Bitki Adları Sözlüğü. Türk Tarih Kurumu Basımevi Ankara. (1994)
(21) Balur Adsız L. The antioxidant activity-controlled isolation of secondary metabolite of Salvia cerino-pruinosa elazigensis’ Dicle Üniversitesi Sağlik Bilimleri Enstitüsü, Diyarbakır. (2018)
(22) Ellman GL, Courtney KD, Andres V and Featherstone RM. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem. Pharmacol. (1961) 7: 88-95.
(23) Hina Z, Ghazala HR, Arfa K, Huma S, Sabiha T and Ajmal K. Anti-urease Activity of Mimusops elengi Linn (Sapotaceae). J. Med. Plants. (2015) 6: 223-230.
(24) Hearing VJ and Jimenez M. Mammalian tyrosinase-the critical regulatory control point in melanocyte pigmentation. Int. J. Biochem. (1987) 19: 1141-1147.
(25) Khan KM, Mughal UR, Khan MTH, Ullah Z, Perveen S, Choudharya MI. Oxazolones: New tyrosinase inhibitors; synthesis and their structure–activity relationships. Bioorg. Med. Chem. (2006) 14: 6027–6033.
(26) Duan Y, Wu C, Chowdhury S, Lee MC, Xiong GM, Zhang W, Yang R, Cieplak P, Luo R, Lee T, Caldwell J, Wang MJ and Kollman P. Point-charge force field for molecular mechanics simulations of proteins based on condensed-phase quantum mechanical calculations. J. Comput. Chem.(2003) 24: 1999-2012.
(27) Case DA, Cheatham TE, Darden T, Gohlke H, Luo R, Merz KM, Onufriev A, Simmerling C, Wang B and Woods RJ. The Amber biomolecular simulation programs. J. Comput. Chem. (2005) 26: 1668-1688.
(28) Bayly CI, Cieplak P, Cornell WD and Kollman PA. A Well- Behaved Electrostatic Potential Based Method Using harge Restraints for Deriving Atomic Charges-the Resp Model. J. Phys. Chem. (1993) 97: 10269-10280.
(29) Faghihi K, Safakish M, Zebardast T, Hajimandi Z and Zarghi A. Molecular Docking and QSAR Study of 2-Benzoxazolinone, Quinazoline and Diazocoumarin Derivatives as Anti-HIV-1 Agents. Iran J. Pharm. Res. (2019) 18(3): 1253-1263.
(30) Flynn BL. Pharmacologic Management of Alzheimer Disease Part I: Hormonal and Emerging Investigational Drug Therapies. Ann. Pharmacother (1999) 33(2): 178–187.
(31) Goedert M and Spillantini MG. A century of Alzheimer's disease. Science (2006) 80 (314): 777–781.
(32) Maurer K, Volk S and Gerbaldo H. Auguste D and Alzheimer’s disease. The Lancet (1997) 349: 1546-1549.
(33) Martinez-Cruz O and Paredes-Lopez O. Phytochemical profile and nutraceutical potential of chiaseeds (Salvia hispanica L.) by ultra high performance liquid chromatography. J. Chromatogr. A (2014)  1346: 43-48.
(34) Orhan I, Kartal M, Naz Q, Ejaz A, Yilmaz G, Kan Y, Konuklugil B, Sener B and Choudhary MI. Antioxidant and anticholinesterase evaluation of selected Turkish Salvia species. Food Chem. (2007) 103(4): 1247-1254.
(35) Demirezer LO, Gurbuz P, Kelicen Ugur EP, Bodur M, Ozenver N, Uz A and Güvenalp Z. Molecular docking and ex vivo and in vitro anticholinesterase activity studies of Salvia sp. And highlighted rosmarinic acid. Turk. J. Med. Sci. (2015) 45: 1141-1148
(36) Topcu G, Ozturk M, Kusman T, Barla Demirkoz AA, Kolak U and Ulubelen A. Terpenoids, essential oil composition and fatty acids profile and biological activities of Anatolian Salvia fruticosa Mill. Turk. J. Med. Sci. (2013) 37(4): 619-632.
(37) Duru ME, Tel G, Ozturk M and Harmandar M. Chemical Composition, Antioxidant and Anticholinesterase Activities of the Essential Oil of Salvia chrysophylla Staph. Rec. Nat. Prod. (2012)  6(2): 175-179.
(38) Tuncer H. Utilization of wild plants as medicine, Vol. II, Editor, Atak Printhouse, The Ministry of Food and Agriculture, Ankara. (1978).
(39) Ramirez J, Suarez AI, Bec N, Armijos C, Gilardoni G, Larroque C and Vidari G. Carnosol from Lepechinia mutica and tiliroside from Vallea stipularis: Two promising inhibitors of BuChE. Rev. Bras. Farmacogn. (2018) 28(5): 559-563.
(40) Szwajgier D. Anticholinesterase Activity of Phenolic Acids and their Derivatives. Zeitschrift für Naturforschung C-A Journal of Biosciences, (2013) 68(3-4): 125-132.
(41) Zhou Y, Li W, Xu L and Chen L. In Salvia miltiorrhiza, phenolic acids possess protective properties against amyloid b-induced cytotoxicity and tanshinones act as acetylcholinesterase inhibitors. Eur. J. Pharmacol. (2011) 31: 443-452.
(42) Kim YS, Kang SS, Ko KH and Ryu JH. Tanshinone congeners improve memory impairments induced by scopolamine on passive avoidance tasks in mice. Eur. J. Pharmacol. (2007) 574: 140-147.
(43) Zengin G, Senkardes I, Mollica A, Picot-Allain CMN, Bulut G, Dogan A and Mahomoodally MF. New insights into the in vitro biological effects, in silico docking and chemical profile of clary Sage-Salvia sclarea L. Comput. Biol. Chem. (2018) 75: 111-119.
(44) Orhan Erdogan I, Senol FS, Ozturk N, Akaydin G and Sener B. Profiling of in vitro neurobiological effects and phenolic acids of selected endemic Salvia species. Food Chem. (2012) 132(3). 1360-1367.
(45) Huang YL and Chau CF. Improvement in intestinal function of hamsters as influenced by consumption of polysaccharide-rich sage weed extracts. Food Chem. (2012) 133: 1618-1623.
(46) Lipinski CA, Lombardo F, Dominy BW and Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug. Deliv. Rev. (1997) 23: 3-25.