Thymol Chemistry: A Medicinal Toolbox

Author(s): Jyoti, Divya Dheer, Davinder Singh, Gulshan Kumar, Manvika Karnatak, Suresh Chandra, Ved Prakash Verma, Ravi Shankar*.

Journal Name: Current Bioactive Compounds

Volume 15 , Issue 5 , 2019

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Graphical Abstract:


Abstract:

Background: Thymol is a natural phenolic monoterpenoid widely used in pharmaceutical and food preservative applications. Thymol isomeric with carvacrol, extracted primarily from Thymus species (Trachyspermum ammi) and other plants sources such as Baccharisgrise bachii and Centipeda minima, has ethnopharmacological characteristics.

Methods: This review was prepared by analyzing articles published on thymol moiety in last decade and selected from Science Direct, Scopus, Pub Med, Web of Science and SciFinder. The selected articles are classified and gives brief introduction about thymol and its isolation, illustrates its natural as well as synthetic sources, and also therapeutic benefits of thymol worldwide

Results: Thymol has been covering different endeavors such as antimicrobial, antioxidant, antiinflammatory, antibacterial, antifungal, antidiarrhoeal, anthelmintic, analgesic, digestive, abortifacient, antihypertensive, spermicidal, depigmenting, antileishmanial, anticholinesterase, insecticidal and many others. This phenolic compound is among the essential scaffolds for medicinal chemists to synthesize more bio-active molecules by further derivatization of the thymol moiety.

Conclusion: Thymol is an interesting scaffold due to its different activities and derivatization of thymol is proved to enhance its biological activities. However, more robust, randomised, controlled clinical trials would be desirable with well-characterised thymol preparations to corroborate its beneficial effects in diseased patients. Moreover, in view of the potential use of thymol and thymol-rich essential oils in the treatment of human infections, comprehensive studies on chronic and acute toxicity and also teratogenicity are to be recommended.

Keywords: GC-MS analysis, carvacrol, thymol, Thymus species, monoterpene, carvacrol.

[1]
Butler, M.S.; Robertson, A.A.; Cooper, M.A. Natural product and natural product derived drugs in clinical trials. Nat. Prod. Rep., 2014, 31(11), 1612-1661.
[http://dx.doi.org/10.1039/C4NP00064A] [PMID: 25204227]
[2]
Agarwal, P.; Fatima, A.; Singh, P.P. Herbal medicine scenario in India and European countries. J. Pharmacogn. Phytochem., 2012, 1(4), 88-93.
[3]
Wagner, K.H.; Elmadfa, I. Effects of tocopherols and their mixtures on the oxidative stability of olive oil and linseed oil under heating. Eur. J. Lipid Sci. Technol., 2000, 102(10), 624-629.
[http://dx.doi.org/10.1002/1438-9312(200010)102:10<624:AID-EJLT624>3.0.CO;2-I]
[4]
Sharkey, T.D.; Yeh, S. Isoprene emission from plants. Annu. Rev. Plant Physiol. Plant Mol. Biol., 2001, 52(1), 407-436.
[http://dx.doi.org/10.1146/annurev.arplant.52.1.407] [PMID: 11337404]
[5]
Chappell, J. Biochemistry and molecular biology of the isoprenoid biosynthetic pathway in plants. Annu. Rev. Plant Physiol. Plant Mol. Biol., 1995, 46(1), 521-547.https://www.annualreviews.org/doi/abs/10.1146/annurev.pp.46.060195.002513
[6]
Sfaei-Ghomi, J.; Meshkatalsadat, M.H.; Shamai, S.; Hasheminejad, M.; Hassani, A. Chemical characterization of bioactive volatile molecules of four Thymus species using nanoscale injection method. Dig. J. Nanomater. Biostruct., 2009, 4(4), 835-841.
[7]
Pathak, A.; Nainwal, N.; Goyal, B.; Singh, R.; Mishra, V.; Nayak, S.; Bansal, P.; Gupta, V. Pharmacological activity of Trachyspermum ammi: a review. J. Pharm. Res., 2010, 3(4), 895-899.
[8]
Hadad, M.; Zygadlo, J.A.; Lima, B. Derita, Feresin, M.E.G.; Zacchino, S. A.; Tapia, A. Chemical composition and antimicrobial activity of essential oil from Baccharis grisebachii Hieron (Asteraceae). J. Chil. Chem. Soc., 2007, 52(2), 1186-1189.
[http://dx.doi.org/10.4067/S0717-97072007000200015]
[9]
Huang, S.; Chiu, C.; Lin, T.; Lee, M.; Lee, C.; Chang, S.; Hou, W.; Huang, G.; Deng, J. Antioxidant and anti-inflammatory activities of aqueous extract of Centipedaminima. J. Ethnopharmacol., 2013, 147(2), 395-405.
[10]
Mathela, C.; Tiwari, A.; Padalia, R.; Chanotiya, C. Chemical composition of Inula cuspidata CB Clarke. 2008, 47B, 1249-1253.
[11]
Weremczuk-Jeżyna, I.; Kisiel, W.; Wysokińska, H. Thymol derivatives from hairy roots of Arnica montana. Plant Cell Rep., 2006, 25(9), 993-996.
[http://dx.doi.org/10.1007/s00299-006-0157-y] [PMID: 16586074]
[12]
Sapkale, G.; Patil, S.; Surwase, U.; Bhatbhage, P. Supercritical fluid extraction: A review. Int. J. Chem. Sci., 2010, 8(2), 110-112.
[13]
Villanueva Bermejo, D.; Angelov, I.; Vicente, G.; Stateva, R.P.; Rodriguez García-Risco, M.; Reglero, G.; Ibañez, E.; Fornari, T. Extraction of thymol from different varieties of thyme plants using green solvents. J. Sci. Food Agric., 2015, 95(14), 2901-2907.
[http://dx.doi.org/10.1002/jsfa.7031] [PMID: 25445203]
[14]
Ashnagar, A.; Gharib Naseri, N.; Ramazani, M. Characterization of the major chemical compounds found in Thymus vulgaris plant grown wildly in Chahar Mahal and Bakhtiari province of Iran. Int. J. Pharm. Tech. Res., 2011, 3, 1-4.
[15]
Trivedi, M. Mass spectrometric analysis of isotopic abundance ratio in biofield energy treated thymol. Front. Appl. Chem., 2016, 1(1), 1-8.
[16]
Li, K.; Yuan, J.; Su, W. Determination of liquiritin, naringin, hesperidin, thymol, imperatorin, honokiol, isoimperatorin, and magnolol in the traditional Chinese medicinal preparation Huoxiang-zhengqi liquid using high-performance liquid chromatography. Yakugaku Zasshi, 2006, 126(11), 1185-1190.
[http://dx.doi.org/10.1248/yakushi.126.1185] [PMID: 17077620]
[17]
Al–Maqtari, M.; Alghalibi, S.M.; Alhamzy, E.H. Chemical composition y antimicrobial activity of essential oil of Thymus vulgaris from Yemen. Turkish J. Biochem., 2011, 36, 342-349.
[18]
Salama, A.; Sabry, R.M.; Eldin, M.S. Response of the newly introduced plant species Monarda citriodora in Egypt to nitrogen fertilization and plant density. Int. J. Pharm. Tech. Res., 2016, 9, 67-77.
[19]
Novy, P.; Davidova, H.; Serrano-Rojero, C.S.; Rondevaldova, J.; Pulkrabek, J.; Kokoska, L. Composition and antimicrobial activity of Euphrasia rostkoviana Hayne essential oil. Evid. Based Complement. Alternat. Med., 2015. 2015734101
[http://dx.doi.org/10.1155/2015/734101] [PMID: 26000025]
[20]
Chahal, K.; Dhaiwal, K.; Kumar, A.; Kataria, D.; Singla, N. Chemical composition of Trachyspermum ammi L. and its biological properties: A review. J. Pharmacogn. Phytochem., 2017, 6(3), 131-140.
[21]
Elezi, F.; Plaku, F.; Ibraliu, A.; Stefkov, G.; Karapandzova, M.; Kulevanova, S.; Aliu, S. Genetic variation of oregano (Origanum vulgare L.) for etheric oil in Albania. Agric. Sci., 2013, 4(09), 449.
[22]
Yamanaka, T. Catalytic Properties of Metal Sulfates Supported on γ-Al2O3 in the Liquid-Phase Isopropylation of m-Cresol with Propylene. Bull. Chem. Soc. Jpn., 1976, 49(10), 2669-2673.
[http://dx.doi.org/10.1246/bcsj.49.2669]
[23]
Grabowska, H.; Miśta, W.; Trawczyński, J.; Wrzyszcz, J.; Zawadzki, M. A method for obtaining thymol by gas phase catalytic alkylation of m-cresol over zinc aluminate spinel. Appl. Catal. A Gen., 2001, 220(1), 207-213.
[http://dx.doi.org/10.1016/S0926-860X(01)00722-0]
[24]
Amandi, R.; Hyde, J.R.; Ross, S.K.; Lotz, T.J.; Poliakoff, M. Continuous reactions in supercritical fluids; a cleaner, more selective synthesis of thymol in supercritical CO2. Green Chem., 2005, 7(5), 288-293.
[http://dx.doi.org/10.1039/b418983c]
[25]
Wimmer, P.; Buysch, H-J.; Puppe, L. Process for the preparation of thymol U.S. Patent 4086283A, July 30. 1991.
[26]
Bottoms, R.R. Production of thymol; Google Patents, U.S. Patent 2840616A, June 24. 1958.
[27]
Phillips, M.; Gibbs, H. A Synthesis of Thymol from p-Cymene. Ind. Eng. Chem., 1920, 12(8), 733-734.
[http://dx.doi.org/10.1021/ie50128a007]
[28]
Ali, A.A.; Gaikar, V.G. Microwave-assisted process intensification of synthesis of thymol using Carbonized Sulfonic Acidic resin (CSA) catalyst. Ind. Eng. Chem. Res., 2011, 50(11), 6543-6555.
[http://dx.doi.org/10.1021/ie102053f]
[29]
Velu, S.; Sivasanker, S. Alkylation of m-cresol with methanol and 2-propanol over calcined magnesium-aluminium hydrotalcites. Res. Chem. Intermed., 1998, 24(6), 657-666.
[http://dx.doi.org/10.1163/156856798X00555]
[30]
Crane, E.A.; Gademann, K. Capturing biological activity in natural product fragments by chemical synthesis. Angew. Chem. Int. Ed. Engl., 2016, 55(12), 3882-3902.
[http://dx.doi.org/10.1002/anie.201505863] [PMID: 26833854]
[31]
Kaur, R.; Ruhil, S.; Balhara, M.; Dhankhar, S.; Chhillar, A. A review on Justicia adhatoda: A potential source of natural medicine. Afri. J. Plant Sci., 2013, 5(11), 620-627.
[32]
Miladi, H.; Zmantar, T.; Kouidhi, B.; Chaabouni, Y.; Mahdouani, K.; Bakhrouf, A.; Chaieb, K. Use of carvacrol, thymol, and eugenol for biofilm eradication and resistance modifying susceptibility of Salmonella enterica serovar Typhimurium strains to nalidixic acid. Microb. Pathog., 2017, 104, 56-63.
[http://dx.doi.org/10.1016/j.micpath.2017.01.012] [PMID: 28062292]
[33]
Aly, A.H.; Saad, R.E-Z.; Ahmed, K.A-K. Synthesis of thymol derivatives as potential non-irritant antimicrobial and insecticidal agents. Curr. Bioact. Compd., 2017, 13, 1-13.
[34]
Marchese, A.; Orhan, I.E.; Daglia, M.; Barbieri, R.; Di Lorenzo, A.; Nabavi, S.F.; Gortzi, O.; Izadi, M.; Nabavi, S.M. Antibacterial and antifungal activities of thymol: A brief review of the literature. Food Chem., 2016, 210, 402-414.
[http://dx.doi.org/10.1016/j.foodchem.2016.04.111] [PMID: 27211664]
[35]
Botelho, M.A.; Nogueira, N.A.; Bastos, G.M.; Fonseca, S.G.; Lemos, T.L.; Matos, F.J.; Montenegro, D.; Heukelbach, J.; Rao, V.S.; Brito, G.A. Antimicrobial activity of the essential oil from Lippia sidoides, carvacrol and thymol against oral pathogens. Braz. J. Med. Biol. Res., 2007, 40(3), 349-356.
[http://dx.doi.org/10.1590/S0100-879X2007000300010] [PMID: 17334532]
[36]
Desai, J.; Shah, V. Synthesis and biological activity of cyanopyridine, isoxazole and pyrazoline derivatives having thymol moiety. Indian J. Chem., 2003, 42, 382-385.
[http://dx.doi.org/10.1002/chin.200322137]
[37]
Roda, K.; Vansdadia, R.; Parekh, H. Studies on 1, 3, 4-oxadiazoles. 2. preparation and antimicrobial activity of 2-benzoyl-amino-5-(2′-isopropyl-5′-methylphenoxy-methyl)-1, 3, 4-oxadiazoles. Ind. Chem. Soc., 1988, 65, 807-809.
[38]
Zhao, J.; Li, Y.; Liu, Q.; Gao, K. Antimicrobial activities of some thymol derivatives from the roots of Inula hupehensis. Food Chem., 2010, 120(2), 512-516.
[http://dx.doi.org/10.1016/j.foodchem.2009.10.045]
[39]
Inci Gul, H.; Yamali, C.; Tugce Yasa, A.; Unluer, E.; Sakagami, H.; Tanc, M.; Supuran, C.T. Carbonic anhydrase inhibition and cytotoxicity studies of Mannich base derivatives of thymol. J. Enzyme Inhib. Med. Chem., 2016, 31(6), 1375-1380.
[http://dx.doi.org/10.3109/14756366.2016.1140755] [PMID: 26850788]
[40]
Nagle, P.; Pawar, Y.; Sonawane, A.; Bhosale, S.; More, D. Synthesis and evaluation of antioxidant and antimicrobial properties of thymol containing pyridone moieties. Med. Chem. Res., 2012, 21(7), 1395-1402.
[http://dx.doi.org/10.1007/s00044-011-9656-7]
[41]
Shankar, R.; Chakravarti, B.; Singh, U.S.; Ansari, M.I.; Deshpande, S.; Dwivedi, S.K.D.; Bid, H.K.; Konwar, R.; Kharkwal, G.; Chandra, V.; Dwivedi, A.; Hajela, K. Synthesis and biological evaluation of 3,4,6-triaryl-2-pyranones as a potential new class of anti-breast cancer agents. Bioorg. Med. Chem., 2009, 17(11), 3847-3856.
[http://dx.doi.org/10.1016/j.bmc.2009.04.032] [PMID: 19423356]
[42]
Nostro, A.; Blanco, A.R.; Cannatelli, M.A.; Enea, V.; Flamini, G.; Morelli, I.; Sudano Roccaro, A.; Alonzo, V. Susceptibility of methicillin-resistant staphylococci to oregano essential oil, carvacrol and thymol. FEMS Microbiol. Lett., 2004, 230(2), 191-195.
[http://dx.doi.org/10.1016/S0378-1097(03)00890-5] [PMID: 14757239]
[43]
Dong, L-M.; Zhang, M.; Xu, Q-L.; Zhang, Q.; Luo, B.; Luo, Q-W.; Liu, W-B.; Tan, J-W. Two new thymol derivatives from the roots of Ageratina adenophora. Molecules, 2017, 22(4), 592.
[http://dx.doi.org/10.3390/molecules22040592] [PMID: 28397757]
[44]
Liang, H.; Bao, F.; Dong, X.; Tan, R.; Zhang, C.; Lu, Q.; Cheng, Y. Antibacterial thymol derivatives isolated from Centipeda minima. Molecules, 2007, 12(8), 1606-1613.
[http://dx.doi.org/10.3390/12081606] [PMID: 17960076]
[45]
Epps, S.V.; Harvey, R.B.; Byrd, J.A.; Petrujkić, B.T.; Sedej, I.; Beier, R.C.; Phillips, T.D.; Hume, M.E.; Anderson, R.C.; Nisbet, D.J. Comparative effect of thymol or its glucose conjugate, thymol-β-D-glucopyranoside, on Campylobacter in avian gut contents. J. Environ. Sci. Health B, 2015, 50(1), 55-61.
[http://dx.doi.org/10.1080/03601234.2015.965634] [PMID: 25421628]
[46]
Yanishlieva, N.V.; Marinova, E.M.; Gordon, M.H.; Raneva, V.G. Antioxidant activity and mechanism of action of thymol and carvacrol in two lipid systems. Food Chem., 1999, 64(1), 59-66.
[http://dx.doi.org/10.1016/S0308-8146(98)00086-7]
[47]
Beena; Kumar, D.; Rawat, D.S. Synthesis and antioxidant activity of thymol and carvacrol based Schiff bases. Bioorg. Med. Chem. Lett., 2013, 23(3), 641-645.
[http://dx.doi.org/10.1016/j.bmcl.2012.12.001] [PMID: 23273412]
[48]
Javan, A.J.; Javan, M.J. Electronic structure of some thymol derivatives correlated with the radical scavenging activity: Theoretical study. Food Chem., 2014, 165, 451-459.
[http://dx.doi.org/10.1016/j.foodchem.2014.05.073] [PMID: 25038698]
[49]
Ashraf, Z.; Rafiq, M.; Seo, S-Y.; Kwon, K.S.; Babar, M.M.; Zaidi, N.U. Kinetic and in silico studies of novel hydroxy-based thymol analogues as inhibitors of mushroom tyrosinase. Eur. J. Med. Chem., 2015, 98, 203-211.
[http://dx.doi.org/10.1016/j.ejmech.2015.05.031] [PMID: 26025140]
[50]
Dheer, D. Jyoti; Gupta, P.N.; Shankar, R. Tacrolimus: An updated review on delivering strategies for multifarious diseases. Eur. J. Pharm. Sci., 2018, 114, 217-227.
[http://dx.doi.org/10.1016/j.ejps.2017.12.017] [PMID: 29277665]
[51]
Celebioglu, A.; Yildiz, Z.I.; Uyar, T. Thymol/cyclodextrin inclusion complex nanofibrous webs: Enhanced water solubility, high thermal stability and antioxidant property of thymol; Food Res. Inter, 2017, pp. 280-290.
[52]
Kfoury, M.; Landy, D.; Ruellan, S.; Auezova, L.; Greige-Gerges, H.; Fourmentin, S. Determination of formation constants and structural characterization of cyclodextrin inclusion complexes with two phenolic isomers: Carvacrol and thymol. Beilstein J. Org. Chem., 2016, 12, 29-42.
[http://dx.doi.org/10.3762/bjoc.12.5] [PMID: 26877806]
[53]
Dheer, D.; Rawal, R.K.; Singh, V.; Sangwan, P.; Das, P.; Shankar, R. β-CD/CuI catalyzed regioselective synthesis of iodo substituted 1, 2, 3-triazoles, imidazo [1, 2-a]-pyridines and benzoimidazo [2, 1-b] thiazoles in water and their functionalization. Tetrahedron, 2017, 73(30), 4295-4306.
[http://dx.doi.org/10.1016/j.tet.2017.05.081]
[54]
Deng, L-L.; Taxipalati, M.; Que, F.; Zhang, H. Physical characterization and antioxidant activity of thymol solubilized Tween 80 micelles. Sci. Rep., 2016, 6, 38160.
[http://dx.doi.org/10.1038/srep38160] [PMID: 27905567]
[55]
Dixon, D.M.; Walsh, T.J. Antifungal agents. In: Medical Microbiology, 4th ed; University of Texas Medical Branch at Galveston: Texas, USA, 1996.
[56]
Webster, D.; Taschereau, P.; Belland, R.J.; Sand, C.; Rennie, R.P. Antifungal activity of medicinal plant extracts; preliminary screening studies. J. Ethnopharmacol., 2008, 115(1), 140-146.
[http://dx.doi.org/10.1016/j.jep.2007.09.014] [PMID: 17996411]
[57]
de Castro, R.D.; de Souza, T.M.P.A.; Bezerra, L.M.D.; Ferreira, G.L.S.; Costa, E.M.; Cavalcanti, A.L. Antifungal activity and mode of action of thymol and its synergism with nystatin against Candida species involved with infections in the oral cavity: An in vitro study. BMC Complement. Altern. Med., 2015, 15(1), 417.
[http://dx.doi.org/10.1186/s12906-015-0947-2] [PMID: 26601661]
[58]
Guo, N.; Liu, J.; Wu, X.; Bi, X.; Meng, R.; Wang, X.; Xiang, H.; Deng, X.; Yu, L. Antifungal activity of thymol against clinical isolates of fluconazole-sensitive and -resistant Candida albicans. J. Med. Microbiol., 2009, 58(Pt 8), 1074-1079.
[http://dx.doi.org/10.1099/jmm.0.008052-0] [PMID: 19528168]
[59]
de Lira Mota, K.S.; de Oliveira Pereira, F.; de Oliveira, W.A.; Lima, I.O.; de Oliveira Lima, E. Antifungal activity of Thymus vulgaris L. essential oil and its constituent phytochemicals against Rhizopus oryzae: Interaction with ergosterol. Molecules, 2012, 17(12), 14418-14433.
[http://dx.doi.org/10.3390/molecules171214418] [PMID: 23519243]
[60]
Cui, Z.; Li, X.; Nishida, Y. Synthesis and bioactivity of novel carvacrol and thymol derivatives containing 5-phenyl-2-furan. Lett. Drug Des. Discov., 2014, 11(7), 877-885.
[http://dx.doi.org/10.2174/1570180811666140220005252]
[61]
Chauhan, K.R.; Le, T.C.; Chintakunta, P.K.; Lakshman, D.K. Phyto-fungicides: Structure activity relationships of the thymol derivatives against Rhizoctonia solani. J. Agri. Chem. Envir., 2017, 6(04), 175.
[62]
Kaur, H.; Lim, S.M.; Ramasamy, K.; Vasudevan, M.; Shah, S.A.A.; Narasimhan, B. Diazenyl schiff bases: Synthesis, spectral analysis, antimicrobial studies and cytotoxic activity on human colorectal carcinoma cell line (HCT-116). Arab. J. Chem., 2017.
[http://dx.doi.org/10.1016/j.arabjc.2017.05.004]
[63]
Ferreira, L.E.; Benincasa, B.I.; Fachin, A.L.; França, S.C.; Contini, S.S.H.T.; Chagas, A.C.S.; Beleboni, R.O. Thymus vulgaris L. essential oil and its main component thymol: Anthelmintic effects against Haemonchus contortus from sheep. Vet. Parasitol., 2016, 228, 70-76.
[http://dx.doi.org/10.1016/j.vetpar.2016.08.011] [PMID: 27692335]
[64]
Boubaker Elandalousi, R.; Akkari, H.; B’chir, F.; Gharbi, M.; Mhadhbi, M.; Awadi, S.; Darghouth, M.A. Thymus capitatus from Tunisian arid zone: Chemical composition and in vitro anthelmintic effects on Haemonchus contortus. Vet. Parasitol., 2013, 197(1-2), 374-378.
[http://dx.doi.org/10.1016/j.vetpar.2013.05.016] [PMID: 23768565]
[65]
Albani, C.M.; Pensel, P.E.; Elissondo, N.; Gambino, G.; Elissondo, M.C. In vivo activity of albendazole in combination with thymol against Echinococcus multilocularis. Vet. Parasitol., 2015, 212(3-4), 193-199.
[http://dx.doi.org/10.1016/j.vetpar.2015.06.030] [PMID: 26190130]
[66]
Carvalho, C.O.; Chagas, A.C.S.; Cotinguiba, F.; Furlan, M.; Brito, L.G.; Chaves, F.C.; Stephan, M.P.; Bizzo, H.R.; Amarante, A.F. The anthelmintic effect of plant extracts on Haemonchus contortus and Strongyloides venezuelensis. Vet. Parasitol., 2012, 183(3-4), 260-268.
[http://dx.doi.org/10.1016/j.vetpar.2011.07.051] [PMID: 21872995]
[67]
Moazeni, M.; Saharkhiz, M.J.; Hosseini, A.A. In vitro lethal effect of ajowan (Trachyspermum ammi L.) essential oil on hydatid cyst protoscoleces. Vet. Parasitol., 2012, 187(1-2), 203-208.
[http://dx.doi.org/10.1016/j.vetpar.2011.12.025] [PMID: 22245070]
[68]
Yones, D.A.; Taher, G.A.; Ibraheim, Z.Z. In vitro effects of some herbs used in Egyptian traditional medicine on viability of protoscolices of hydatid cysts. Korean J. Parasitol., 2011, 49(3), 255-263.
[http://dx.doi.org/10.3347/kjp.2011.49.3.255] [PMID: 22072825]
[69]
Abdel-Rahman, F.H.; Alaniz, N.M.; Saleh, M.A. Nematicidal activity of terpenoids. J. Environ. Sci. Health B, 2013, 48(1), 16-22.
[http://dx.doi.org/10.1080/03601234.2012.716686] [PMID: 23030436]
[70]
Lei, J.; Leser, M.; Enan, E. Nematicidal activity of two monoterpenoids and SER-2 tyramine receptor of Caenorhabditis elegans. Biochem. Pharmacol., 2010, 79(7), 1062-1071.
[http://dx.doi.org/10.1016/j.bcp.2009.11.002] [PMID: 19896925]
[71]
Pensel, P.E.; Maggiore, M.A.; Gende, L.B.; Eguaras, M.J.; Denegri, M.G.; Elissondo, M.C. Efficacy of essential oils of Thymus vulgaris and Origanum vulgare on Echinococcus granulosus. Interdiscip. Perspect. Infect. Dis., 2014, 2014693289
[http://dx.doi.org/10.1155/2014/693289] [PMID: 25180033]
[72]
Botelho, M.A.; Barros, G.; Queiroz, D.B.; Carvalho, C.F.; Gouvea, J.; Patrus, L.; Bannet, M.; Patrus, D.; Rego, A.; Silva, I.; Campus, G.; Araújo-Filho, I. Nanotechnology in phytotherapy: Antiinflammatory effect of a nanostructured thymol gel from Lippia sidoides in acute periodontitis in rats. Phytother. Res., 2016, 30(1), 152-159.
[http://dx.doi.org/10.1002/ptr.5516] [PMID: 26553130]
[73]
Veras, H.N.; Araruna, M.K.; Costa, J.G.; Coutinho, H.D.; Kerntopf, M.R.; Botelho, M.A.; Menezes, I.R. Topical antiinflammatory activity of essential oil of Lippia sidoides cham: Possible mechanism of action. Phytother. Res., 2013, 27(2), 179-185.
[http://dx.doi.org/10.1002/ptr.4695] [PMID: 22511564]
[74]
Palabiyik, S.S.; Karakus, E.; Halici, Z.; Cadirci, E.; Bayir, Y.; Ayaz, G.; Cinar, I. The protective effects of carvacrol and thymol against paracetamol-induced toxicity on human hepatocellular carcinoma cell lines (HepG2). Hum. Exp. Toxicol., 2016, 35(12), 1252-1263.
[http://dx.doi.org/10.1177/0960327115627688] [PMID: 26801986]
[75]
Braga, P.C.; Dal Sasso, M.; Culici, M.; Bianchi, T.; Bordoni, L.; Marabini, L. Anti-inflammatory activity of thymol: Inhibitory effect on the release of human neutrophil elastase. Pharmacology, 2006, 77(3), 130-136.
[http://dx.doi.org/10.1159/000093790] [PMID: 16763380]
[76]
Tsai, M-L.; Lin, C-C.; Lin, W-C.; Yang, C-H. Antimicrobial, antioxidant, and anti-inflammatory activities of essential oils from five selected herbs. Biosci. Biotechnol. Biochem., 2011, 75(10), 1977-1983.
[http://dx.doi.org/10.1271/bbb.110377] [PMID: 21979069]
[77]
Ashraf, Z.; Alamgeer, M.K.; Kanwal, M.; Hassan, M.; Abdullah, S.; Waheed, M.; Ahsan, H.; Kim, S.J. Flurbiprofen-antioxidant mutual prodrugs as safer nonsteroidal anti-inflammatory drugs: Synthesis, pharmacological investigation, and computational molecular modeling. Drug Des. Devel. Ther., 2016, 10, 2401-2419.
[http://dx.doi.org/10.2147/DDDT.S109318] [PMID: 27555750]
[78]
Chandiran, S.; Vyas, S.; Sharma, N.; Sharma, M. Synthesis and evaluation of antioxidant-s-(+)-Ibuprofen hybrids as gastro sparing NSAIDs. Med. Chem., 2013, 9(7), 1006-1016.
[http://dx.doi.org/10.2174/1573406411309070015] [PMID: 23061566]
[79]
Redasani, V.K.; Bari, S.B. Synthesis and evaluation of mutual prodrugs of ibuprofen with menthol, thymol and eugenol. Eur. J. Med. Chem., 2012, 56, 134-138.
[http://dx.doi.org/10.1016/j.ejmech.2012.08.030] [PMID: 22982120]
[80]
Riella, K.R.; Marinho, R.R.; Santos, J.S.; Pereira-Filho, R.N.; Cardoso, J.C.; Albuquerque-Junior, R.L.; Thomazzi, S.M. Anti-inflammatory and cicatrizing activities of thymol, a monoterpene of the essential oil from Lippia gracilis, in rodents. J. Ethnopharmacol., 2012, 143(2), 656-663.
[http://dx.doi.org/10.1016/j.jep.2012.07.028] [PMID: 22885071]
[81]
Marsik, P.; Kokoska, L.; Landa, P.; Nepovim, A.; Soudek, P.; Vanek, T. In vitro inhibitory effects of thymol and quinones of Nigella sativa seeds on cyclooxygenase-1- and -2-catalyzed prostaglandin E2 biosyntheses. Planta Med., 2005, 71(8), 739-742.
[http://dx.doi.org/10.1055/s-2005-871288] [PMID: 16142638]
[82]
Chen, J-J.; Tsai, Y-C.; Hwang, T-L.; Wang, T-C. Thymol, benzofuranoid, and phenylpropanoid derivatives: anti-inflammatory constituents from Eupatorium cannabinum. J. Nat. Prod., 2011, 74(5), 1021-1027.
[http://dx.doi.org/10.1021/np100923z] [PMID: 21391659]
[83]
Nesterkina, M.; Kravchenko, I. Synthesis and pharmacological properties of novel esters based on monoterpenoids and glycine. Pharmaceuticals (Basel), 2017, 10(2), 47.
[http://dx.doi.org/10.3390/ph10020047] [PMID: 28524111]
[84]
Jan, S.A.; Shinwari, Z.K.; Zeb, A.; Khalil, A.T.; Shah, S.H. Ethnobotany and research trends in Trachyspermum ammi L.(Ajowan); A popular folklore remedy. Amer-Eurasian J Agri. Environ. Sci. (Ruse), 2015, 15, 68-73.
[85]
Sargazi Zadeh, G.; Panahi, N. Endothelium-independent vasorelaxant activity of Trachyspermum ammi essential oil on rat aorta. Clin. Exp. Hypertens., 2017, 39(2), 133-138.
[http://dx.doi.org/10.1080/10641963.2016.1235178] [PMID: 28287882]
[86]
Mihailovic-Stanojevic, N.; Belščak-Cvitanović, A.; Grujić-Milanović, J.; Ivanov, M.; Jovović, Dj.; Bugarski, D.; Miloradović, Z. Antioxidant and antihypertensive activity of extract from Thymus serpyllum L. in experimental hypertension. Plant Foods Hum. Nutr., 2013, 68(3), 235-240.
[http://dx.doi.org/10.1007/s11130-013-0368-7] [PMID: 23828496]
[87]
Gilani, A.H.; Jabeen, Q.; Ghayur, M.N.; Janbaz, K.H.; Akhtar, M.S. Studies on the antihypertensive, antispasmodic, bronchodilator and hepatoprotective activities of the Carum copticum seed extract. J. Ethnopharmacol., 2005, 98(1-2), 127-135.
[http://dx.doi.org/10.1016/j.jep.2005.01.017] [PMID: 15763373]
[88]
Briganti, S.; Camera, E.; Picardo, M. Chemical and instrumental approaches to treat hyperpigmentation. Pigment Cell Res., 2003, 16(2), 101-110.
[http://dx.doi.org/10.1034/j.1600-0749.2003.00029.x] [PMID: 12622786]
[89]
Burlando, B.; Clericuzio, M.; Cornara, L. Moraceae plants with tyrosinase inhibitory activity: A review. Mini Rev. Med. Chem., 2017, 17(2), 108-121.
[http://dx.doi.org/10.2174/1389557516666160609071854] [PMID: 27292779]
[90]
Kang, H.H.; Rho, H.S.; Hwang, J.S.; Oh, S-G. Depigmenting activity and low cytotoxicity of alkoxy benzoates or alkoxy cinnamte in cultured melanocytes. Chem. Pharm. Bull. (Tokyo), 2003, 51(9), 1085-1088.
[http://dx.doi.org/10.1248/cpb.51.1085] [PMID: 12951453]
[91]
Pillaiyar, T.; Manickam, M.; Namasivayam, V. Skin whitening agents: Medicinal chemistry perspective of tyrosinase inhibitors. J. Enzyme Inhib. Med. Chem., 2017, 32(1), 403-425.
[http://dx.doi.org/10.1080/14756366.2016.1256882] [PMID: 28097901]
[92]
de Morais, S.M.; Vila-Nova, N.S.; Bevilaqua, C.M.L.; Rondon, F.C.; Lobo, C.H.; de Alencar Araripe Noronha Moura, A.; Sales, A.D.; Rodrigues, A.P.R.; de Figuereido, J.R.; Campello, C.C.; Wilson, M.E.; de Andrade, H.F., Jr Thymol and eugenol derivatives as potential antileishmanial agents. Bioorg. Med. Chem., 2014, 22(21), 6250-6255.
[http://dx.doi.org/10.1016/j.bmc.2014.08.020] [PMID: 25281268]
[93]
Xavier, F.J.S.; Rodrigues, K.A.F.; de Oliveira, R.G.; Lima Junior, C.G., ; Rocha, J.D.; Keesen, T.S.L.; de Oliveira, M.R.; Silva, F.P.L.; Vasconcellos, M.L.A.A. Synthesis and In vitro Anti-Leishmania amazonensis biological screening of morita-baylis-hillman adducts prepared from eugenol, thymol and carvacrol. Molecules, 2016, 21(11), 1483.
[http://dx.doi.org/10.3390/molecules21111483] [PMID: 27834831]
[94]
de Medeiros, Md.; da Silva, A.C.; Citó, A.M.G.L.; Borges, A.R.; de Lima, S.G.; Lopes, J.A.D.; Figueiredo, R.C.B.Q. In vitro antileishmanial activity and cytotoxicity of essential oil from Lippia sidoides Cham. Parasitol. Int., 2011, 60(3), 237-241.
[http://dx.doi.org/10.1016/j.parint.2011.03.004] [PMID: 21421075]
[95]
de Melo, J.O.; Bitencourt, T.A.; Fachin, A.L.; Cruz, E.M.O.; de Jesus, H.C.R.; Alves, P.B.; de Fátima Arrigoni-Blank, M.; de Castro Franca, S.; Beleboni, R.O.; Fernandes, R.P.M.; Blank, A.F.; Scher, R. Antidermatophytic and antileishmanial activities of essential oils from Lippia gracilis Schauer genotypes. Acta Trop., 2013, 128(1), 110-115.
[http://dx.doi.org/10.1016/j.actatropica.2013.06.024] [PMID: 23850505]
[96]
Aponte, J.C.; Jin, Z.; Vaisberg, A.J.; Castillo, D.; Málaga, E.; Lewis, W.H.; Sauvain, M.; Gilman, R.H.; Hammond, G.B. Cytotoxic and anti-infective phenolic compounds isolated from Mikania decora and Cremastosperma microcarpum. Planta Med., 2011, 77(14), 1597-1599.
[http://dx.doi.org/10.1055/s-0030-1270960] [PMID: 21472652]
[97]
Robledo, S.; Osorio, E.; Muñoz, D.; Jaramillo, L.M.; Restrepo, A.; Arango, G.; Vélez, I. In vitro and in vivo cytotoxicities and antileishmanial activities of thymol and hemisynthetic derivatives. Antimicrob. Agents Chemother., 2005, 49(4), 1652-1655.
[http://dx.doi.org/10.1128/AAC.49.4.1652-1655.2005] [PMID: 15793164]
[98]
Osorio, E.; Arango, G.; Robledo, S.; Munoz, D.; Jaramillo, L.; Velez, I. Antileishmanial and cytotoxic activity of synthetic aromatic monoterpens. Lat. Am. J. Pharm., 2007, 25(3), 405.
[99]
Pohanka, M. Inhibitors of acetylcholinesterase and butyrylcholinesterase meet immunity. Int. J. Mol. Sci., 2014, 15(6), 9809-9825.
[http://dx.doi.org/10.3390/ijms15069809] [PMID: 24893223]
[100]
Seo, S-M.; Jung, C-S.; Kang, J.; Lee, H-R.; Kim, S-W.; Hyun, J.; Park, I-K. Larvicidal and acetylcholinesterase inhibitory activities of apiaceae plant essential oils and their constituents against Aedes albopictus and formulation development. J. Agric. Food Chem., 2015, 63(45), 9977-9986.
[http://dx.doi.org/10.1021/acs.jafc.5b03586] [PMID: 26500081]
[101]
Yeom, H-J.; Kang, J.S.; Kim, G-H.; Park, I-K. Insecticidal and acetylcholine esterase inhibition activity of Apiaceae plant essential oils and their constituents against adults of German cockroach (Blattella germanica). J. Agric. Food Chem., 2012, 60(29), 7194-7203.
[http://dx.doi.org/10.1021/jf302009w] [PMID: 22746406]
[102]
Sammi, S.R.; Trivedi, S.; Rath, S.K.; Nagar, A.; Tandon, S.; Kalra, A.; Pandey, R. 1-Methyl-4-propan-2-ylbenzene from Thymus vulgaris Attenuates Cholinergic Dysfunction. Mol. Neurobiol., 2016, 54(7), 5468-5481.
[PMID: 27599497]
[103]
Orhan, I.; Kartal, M.; Kan, Y.; Şener, B. Activity of essential oils and individual components against acetyland butyrylcholinesterase. Z. Naturforsch. C Bio. Sci., 2008, 63(7-8), 547-553.
[PMID: 18810999]
[104]
Kurt, B.Z.; Gazioglu, I.; Dag, A.; Salmas, R.E.; Kayık, G.; Durdagi, S.; Sonmez, F. Synthesis, anticholinesterase activity and molecular modeling study of novel carbamate-substituted thymol/carvacrol derivatives. Bioorg. Med. Chem., 2017, 25(4), 1352-1363.
[http://dx.doi.org/10.1016/j.bmc.2016.12.037] [PMID: 28089589]
[105]
Azizi, Z.; Ebrahimi, S.; Saadatfar, E.; Kamalinejad, M.; Majlessi, N. Cognitive-enhancing activity of thymol and carvacrol in two rat models of dementia. Behav. Pharmacol., 2012, 23(3), 241-249.
[http://dx.doi.org/10.1097/FBP.0b013e3283534301] [PMID: 22470103]
[106]
Hieu, T.T.; Kim, S-I.; Ahn, Y-J. Toxicity of Zanthoxylum piperitum and Zanthoxylum armatum oil constituents and related compounds to Stomoxys calcitrans (Diptera: Muscidae). J. Med. Entomol., 2012, 49(5), 1084-1091.
[http://dx.doi.org/10.1603/ME12047] [PMID: 23025190]
[107]
Park, J-H.; Jeon, Y-J.; Lee, C-H.; Chung, N.; Lee, H-S. Insecticidal toxicities of carvacrol and thymol derived from Thymus vulgaris Lin. against Pochazia shantungensis Chou & Lu., newly recorded pest. Sci. Rep., 2017, 7, 40902.
[http://dx.doi.org/10.1038/srep40902] [PMID: 28106093]
[108]
Grodnitzky, J.A.; Coats, J.R. QSAR evaluation of monoterpenoids’ insecticidal activity. J. Agric. Food Chem., 2002, 50(16), 4576-4580.
[http://dx.doi.org/10.1021/jf0201475] [PMID: 12137478]
[109]
Bustos-Brito, C.; Vázquez-Heredia, V.J.; Calzada, F.; Yépez-Mulia, L.; Calderón, J.S.; Hernández-Ortega, S.; Esquivel, B.; García-Hernández, N.; Quijano, L. Antidiarrheal Thymol Derivatives from Ageratina glabrata. Structure and Absolute Configuration of 10-Benzoyloxy-8,9-epoxy-6-hydroxythymol Isobutyrate. Molecules, 2016, 21(9), 1132.
[http://dx.doi.org/10.3390/molecules21091132] [PMID: 27626392]
[110]
Bustos-Brito, C.; Sánchez-Castellanos, M.; Esquivel, B.; Calderón, J.S.; Calzada, F.; Yepez-Mulia, L.; Hernández-Barragán, A.; Joseph-Nathan, P.; Cuevas, G.; Quijano, L. Structure, absolute configuration, and antidiarrheal activity of a thymol derivative from Ageratina cylindrica. J. Nat. Prod., 2014, 77(2), 358-363.
[http://dx.doi.org/10.1021/np400964w] [PMID: 24502360]
[111]
Siegel, R.L.; Miller, K.D.; Fedewa, S.A.; Ahnen, D.J.; Meester, R.G.S.; Barzi, A.; Jemal, A. Colorectal cancer statistics, 2017. CA Cancer J. Clin., 2017, 67(3), 177-193.
[http://dx.doi.org/10.3322/caac.21395] [PMID: 28248415]
[112]
Kang, S-H.; Kim, Y-S.; Kim, E-K.; Hwang, J-W.; Jeong, J-H.; Dong, X.; Lee, J-W.; Moon, S-H.; Jeon, B-T.; Park, P-J. Anticancer effect of thymol on AGS human gastric carcinoma cells. J. Microbiol. Biotechnol., 2016, 26(1), 28-37.
[http://dx.doi.org/10.4014/jmb.1506.06073] [PMID: 26437948]
[113]
Alobaedi, O.H.; Talib, W.H.; Basheti, I.A. Antitumor effect of thymoquinone combined with resveratrol on mice transplanted with breast cancer. Asian Pac. J. Trop. Med., 2017, 10(4), 400-408.
[http://dx.doi.org/10.1016/j.apjtm.2017.03.026] [PMID: 28552110]
[114]
Chen, L.C.; Lee, T.H.; Sung, P.J.; Shu, C.W.; Lim, Y.P.; Cheng, M.J.; Kuo, W.L.; Chen, J.J. New thymol derivatives and cytotoxic constituents from the root of Eupatorium cannabinum ssp. asiaticum. Chem. Biodivers., 2014, 11(9), 1374-1380.
[http://dx.doi.org/10.1002/cbdv.201300392] [PMID: 25238078]
[115]
Dheer, D.; Singh, V.; Shankar, R. Medicinal attributes of 1,2,3-triazoles: Current developments. Bioorg. Chem., 2017, 71, 30-54.
[http://dx.doi.org/10.1016/j.bioorg.2017.01.010] [PMID: 28126288]
[116]
Mona Diab, A.; Josiane, S.; Marwan, E-S.; Soad, K.A-J.; Rania, A.; Mohammad Amjad, K.; Steve, H. Inhibition of Proliferation and Induction of Apoptosis by Thymoquinone via Modulation of TGF Family, p53, p21 and Bcl-2α in Leukemic Cells. Anticancer. Agents Med. Chem., 2017, 17, 1-6.
[117]
Kulabaş, N.; Tatar, E.; Bingöl Özakpınar, Ö.; Özsavcı, D.; Pannecouque, C.; De Clercq, E.; Küçükgüzel, İ. Synthesis and antiproliferative evaluation of novel 2-(4H-1,2,4-triazole-3-ylthio)acetamide derivatives as inducers of apoptosis in cancer cells. Eur. J. Med. Chem., 2016, 121, 58-70.
[http://dx.doi.org/10.1016/j.ejmech.2016.05.017] [PMID: 27214512]
[118]
Vasudevan, K.; Vembar, S.; Veeraraghavan, K.; Haranath, P.S. Influence of intragastric perfusion of aqueous spice extracts on acid secretion in anesthetized albino rats. Indian J. Gastroenterol., 2000, 19(2), 53-56.
[PMID: 10812814]
[119]
Platel, K.; Srinivasan, K. Studies on the influence of dietary spices on food transit time in experimental rats. Nutr. Res., 2001, 21(9), 1309-1314.
[http://dx.doi.org/10.1016/S0271-5317(01)00331-1]
[120]
Ramakrishna Rao, R.; Platel, K.; Srinivasan, K. In vitro influence of spices and spice-active principles on digestive enzymes of rat pancreas and small intestine. Nahrung, 2003, 47(6), 408-412.
[http://dx.doi.org/10.1002/food.200390091] [PMID: 14727769]
[121]
Hashemipour, H.; Kermanshahi, H.; Golian, A.; Khaksar, V. Effects of carboxy methyl cellulose and thymol + carvacrol on performance, digesta viscosity and some blood metabolites of broilers. J. Anim. Physiol. Anim. Nutr. (Berl.), 2014, 98(4), 672-679.
[http://dx.doi.org/10.1111/jpn.12121] [PMID: 24102759]
[122]
Hashemipour, H.; Kermanshahi, H.; Golian, A.; Veldkamp, T. Effect of thymol and carvacrol feed supplementation on performance, antioxidant enzyme activities, fatty acid composition, digestive enzyme activities, and immune response in broiler chickens. Poult. Sci., 2013, 92(8), 2059-2069.
[http://dx.doi.org/10.3382/ps.2012-02685] [PMID: 23873553]
[123]
Kidd, M.; Modlin, I.M.; Gustafsson, B.I.; Drozdov, I.; Hauso, O.; Pfragner, R. Luminal regulation of normal and neoplastic human EC cell serotonin release is mediated by bile salts, amines, tastants, and olfactants. Am. J. Physiol. Gastrointest. Liver Physiol., 2008, 295(2), G260-G272.
[http://dx.doi.org/10.1152/ajpgi.00056.2008] [PMID: 18556422]
[124]
Jindal, D.P.; Coumar, M.S.; Nandakumar, K.; Bodhankar, S.L.; Purohit, P.G.; Mahadik, K.R.; Bruni, G.; Collavoli, E.; Massarelli, P. Synthesis, β-adrenergic blocking activity and β-receptor binding affinities of 1-substituted-3-(2-isopropyl-5-methyl-phenoxy)-propan-2-ol oxalates. Farmaco, 2003, 58(8), 557-562.
[http://dx.doi.org/10.1016/S0014-827X(03)00083-1] [PMID: 12875885]
[125]
Hejazian, S.H.; Bagheri, S.M.; Safari, F. Spasmolytic and anti-spasmodic action of Trachyspermum ammi essence on rat’s ileum contraction. N. Am. J. Med. Sci., 2014, 6(12), 643-647.
[http://dx.doi.org/10.4103/1947-2714.147982] [PMID: 25599053]
[126]
Sethi, N.; Singh, R. Teratological evaluation of some commonly used indigenous antifertility plants in rats. Int. J. Crude Drug Res., 1989, 27(2), 118-120.
[http://dx.doi.org/10.3109/13880208909053949]
[127]
Wagner, T.A.; Liu, J.; Stipanovic, R.D.; Puckhaber, L.S.; Bell, A.A. Hemigossypol, a constituent in developing glanded cottonseed (Gossypium hirsutum). J. Agric. Food Chem., 2012, 60(10), 2594-2598.
[http://dx.doi.org/10.1021/jf2051366] [PMID: 22369216]
[128]
Dheer, D.; Reddy, K.R.; Rath, S.K.; Sangwan, P.; Das, P.; Shankar, R. Cu (I)-catalyzed double C–H amination: synthesis of 2-iodo-imidazo [1, 2-a] pyridines. RSC Advances, 2016, 6(44), 38033-38036.
[http://dx.doi.org/10.1039/C6RA02953A]
[129]
Nagle, P.; Pawar, Y.; Sonawane, A.; Bhosale, S.; More, D. Synthesis, characterisation and in silico studies of 2, 4, 6 trisubstituted pyrimidine containing thymol as a selective adenosine A1 receptor antagonists. J. Pharm. Res., 2011, 4(11), 3915-3918.
[130]
De Silvestro, I.; Drew, S.L.; Nichol, G.S.; Duarte, F.; Lawrence, A.L. Total synthesis of a dimeric thymol derivative isolated from Arnica sachalinensis. Angew. Chem. Int. Ed. Engl., 2017, 56(24), 6813-6817.
[http://dx.doi.org/10.1002/anie.201701481] [PMID: 28474807]
[131]
Radwan, M.; El-Zemity, S.; Mohamed, S.; Sherby, S. Larvicidal activity of some essential oils, monoterpenoids and their corresponding N-methyl carbamate derivatives against Culex pipiens (Diptera: Culicidae). Int. J. Trop. Insect Sci., 2008, 28(2), 61-68.
[http://dx.doi.org/10.1017/S1742758408962366]
[132]
Fachini-Queiroz, F.C.; Kummer, R.; Estevão-Silva, C.F.; Carvalho, M.D.B.; Cunha, J.M.; Grespan, R.; Bersani-Amado, C.A.; Cuman, R.K.N. Effects of thymol and carvacrol, constituents of Thymus vulgaris L. essential oil, on the inflammatory response. Evid. Based Complement. Alternat. Med., 2012, 2012 657026
[http://dx.doi.org/10.1155/2012/657026] [PMID: 22919415]
[133]
Cornaghi, L.; Arnaboldi, F.; Calò, R.; Landoni, F.; Baruffaldi Preis, W.F.; Marabini, L.; Donetti, E. Effects of uv rays and thymol/thymus vulgaris l. Extract in an ex vivo human skin model: Morphological and genotoxicological assessment. Cells Tissues Organs, 2016, 201(3), 180-192.
[http://dx.doi.org/10.1159/000444361] [PMID: 27023828]
[134]
Knudsen, C.L. Device with compositions for delivery to the lungs, the oral mucosa and the brain. AU Patent 2015308546A1. 2015.
[135]
Lotfi, P.; Yaghmaei, P.; Ebrahim-Habibi, A. Cymene and Metformin treatment effect on biochemical parameters of male NMRI mice fed with high fat diet. J. Diabetes Metab. Disord., 2015, 14(1), 52.
[http://dx.doi.org/10.1186/s40200-015-0182-x] [PMID: 26146609]


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