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Hepatoprotective Essential Oils: A Review

  • Daoudi, Nour Elhouda (Laboratory of Bioressources, Biotechnology, Ethnopharmacology and Health, Department of Biology, Faculty of Sciences, University Mohamed Ist) ;
  • Bnouham, Mohamed (Laboratory of Bioressources, Biotechnology, Ethnopharmacology and Health, Department of Biology, Faculty of Sciences, University Mohamed Ist)
  • Received : 2018.12.22
  • Accepted : 2020.08.28
  • Published : 2020.09.30

Abstract

Objectives: Several toxins and molecules are able to damage the liver, causing the hepato-toxicity. This disorder can be protected naturally, by some essential oils obtained from different plants. In this review we are cited some of these compounds that have been tested by their hepatoprotective effect. Methods: We reviewed 83 articles published between 1981 and 2018 in English via three databases Sciencedirect, Springer and PubMed. So, we have used the keywords: Hepatoprotective effect, liver disease, plants and essential oils. Results and conclusion: In this work, we classified the plants; contain the essential oils, in alphabetical order as a table containing the scientific, family names, information plants, the experimental assay and the results obtained from the hepatoprotective studies. We have described 27 species belonging to 12 families: Lamiaceae (7 species), Asteraceae (6 species), Umbellifereae (3 species), Apiaceae (3 species) are the main families which enclose the species that was studied. The study also includes the major compounds isolated from some of these essential oils. The most of those compounds belong to terpene class essentially cineol, carvacrol and thymol. Thus, the different essential oils that have been cited in this review were shown that have an antioxidant activity.

Keywords

References

  1. Bakkali F, Averbeck S, Averbeck D, Idaomar M. Biological effects of essential oils--a review. Food Chem Toxicol. 2008;46(2):446-75. https://doi.org/10.1016/j.fct.2007.09.106
  2. Gaire S, O'Connell M, Holguin FO, Amatya A, Bundy S, Romero A. Insecticidal properties of essential oils and some of their constituents on the Turkestan cockroach (Blattodea: Blattidae). J Econ Entomol. 2017;110(2):584-592. https://doi.org/10.1093/jee/tox035
  3. Burt S. Essential oils: their antibacterial properties and potential applications in foods--a review. Int J Food Microbiol. 2004;94(3):223-53. https://doi.org/10.1016/j.ijfoodmicro.2004.03.022
  4. Bouchra C, Achouri M, Idrissi Hassani LM, Hmamouchi M. Chemical composition and antifungal activity of essential oils of seven Moroccan Labiatae against Botrytis cinerea Pers: Fr. J Ethnopharmacol. 2003;89(1):165-9. https://doi.org/10.1016/S0378-8741(03)00275-7
  5. Musana KA, Yale SH, Abdulkarim AS. Tests of liver injury. Clin Med Res. 2004;2(2):129-31. https://doi.org/10.3121/cmr.2.2.129
  6. Grespan R, Aguiar RP, Giubilei FN, Fuso RR, Damiao MJ, Silva EL, et al. Hepatoprotective effect of pretreatment with Thymus vulgaris essential oil in experimental model of acetaminopheninduced injury. Evid Based Complement Alternat Med. 2014;2014:954136.
  7. Al-Said MS, Mothana RA, Al-Yahya MM, Rafatullah S, Al-Sohaibani MO, Khaled JM, et al. GC-MS analysis: in vivo hepatoprotective and antioxidant activities of the essential oil of achillea biebersteinii afan. Growing in Saudi Arabia. Evid Based Complement Alternat Med. 2016;2016:1867048.
  8. Fathi H, Lashtoo Aghaee B, Ebrahimzadeh MA. Antioxidant activity and phenolic contents of Achillea wilhemsii. Pharmacologyonline. 2011;2:942-9.
  9. Bashi DS, Fazly Bazzaz BS, Sahebkar A, Karimkhani MM, Ahmadi A. Investigation of optimal extraction, antioxidant, and antimicrobial activities of Achillea biebersteinii and A. wilhelmsii. Pharm Biol. 2012;50(9):1168-76. https://doi.org/10.3109/13880209.2012.662235
  10. Asgary S, Naderi GH, Sarrafzadegan N, Mohammadifard N, Mostafavi S, Vakili R. Antihypertensive and antihyperlipidemic effects of Achillea wilhelmsii. Drugs Exp Clin Res. 2000;26(3):89-93.
  11. Sharififar F, Pournourmohammadi S, Arabnejad M. Immunomodulatory activity of aqueous extract of Achillea wilhelmsii C. Koch in mice. Indian J Exp Biol. 2009;47(8):668-71.
  12. Dadkhah A, Fatemi F, Alipour M, Ghaderi Z, Zolfaghari F, Razdan F. Protective effects of Iranian Achillea wilhelmsii essential oil on acetaminophen-induced oxidative stress in rat liver. Pharm Biol. 2015;53(2):220-7. https://doi.org/10.3109/13880209.2014.913298
  13. Ziyyat A, Legssyer A, Mekhfi H, Dassouli A, Serhrouchni M, Benjelloun W. Phytotherapy of hypertension and diabetes in oriental Morocco. J Ethnopharmacol. 1997;58(1):45-54. https://doi.org/10.1016/S0378-8741(97)00077-9
  14. EL-Hawary S, EL-Shabrawy A, Ezzat S, EL-Shibany F. Gas chromatography-mass spectrometry analysis, hepatoprotective and antioxidant activities of the essential oils of four Libyan herbs. J Med Plants Res. 2013;7(24):1746-53.
  15. Rabeh NM, Aboraya AO. Hepatoprotective effect of Dill (Anethum graveolens L.) and fennel (Foeniculum vulgare) oil on hepatotoxic rats. Pakistan J Nutr. 2014;13(6):303-9. https://doi.org/10.3923/pjn.2014.303.309
  16. Heamalatha S, Swarnalatha S, Divya M, Gandhi Lakshmi R, Ganga Devi A, Gomathi E. Pharmacognostical, pharmacological, investigation on Anethum graveolens Linn: a review. Res J Pharm Biol Chem Sci. 2011;2(4):564-74.
  17. Wang Y, Lou L, Wang J, Lu J, Li J, Jia L. Comparative study on Artemisia halodendron Turcz. and its two related plants by GCMS analysis and protective effect against carbon tetrachlorideinduced hepatotoxicity in mice. Nat Prod Res. 2018;32(11):1303-6. https://doi.org/10.1080/14786419.2017.1340284
  18. Ornano L, Venditti A, Ballero M, Sanna C, Donno Y, Quassinti L, et al. Essential oil composition and biological activity from Artemisia caerulescens subsp. densiflora (Viv.) Gamisans ex Kerguelen & Lambinon (Asteraceae), an endemic species in the habitat of La Maddalena Archipelago. Nat Prod Res. 2016;30(16):1802-9. https://doi.org/10.1080/14786419.2015.1079190
  19. Guetat A, Al-Ghamdi FA, Osman AK. The genus Artemisia L. in the northern region of Saudi Arabia: essential oil variability and antibacterial activities. Nat Prod Res. 2017;31(5):598-603. https://doi.org/10.1080/14786419.2016.1207071
  20. Cha JD, Moon SE, Kim HY, Lee JC, Lee KY. The essential oil isolated from Artemisia capillaris prevents LPS-induced production of NO and PGE(2) by inhibiting MAPK-mediated pathways in RAW 264.7 macrophages. Immunol Invest. 2009;38(6):483-97. https://doi.org/10.1080/08820130902936307
  21. Gao Q, Zhao X, Yin L, Zhang Y, Wang B, Wu X, et al. The essential oil of Artemisia capillaris protects against CCl4-induced liver injury in vivo. Rev Bras Farmacogn. 2016;26(3):369-74. https://doi.org/10.1016/j.bjp.2016.01.001
  22. Tomic A, Bozin B, Samojlik I, Milenkovic M, Mimica-Dukic N, Petrovic S. Effects of Athamanta turbith fruit essential oils on CCl4-induced hepatic failure in mice and their antioxidant properties. Phytother Res. 2010;24(5):787-90. https://doi.org/10.1002/ptr.3036
  23. Mehmood F, Shahzadi P, Khan ZUD, Arshad N, Bilal M, Perveen Z, et al. In Vivo hepatoprotective and antidiabetic activities of essential oils from Boenninghausenia albiflora (Hook.) reichb. ex heynkh, of Pakistan. MOJ Bioequiv Availab. 2017;4(1):211-4.
  24. Blumenthal M, Busse WR. The complete German commission E monographs: therapeutic guide to herbal medicines. Austin: American Botanical Council; 1999. 685 p.
  25. Samojlik I, Lakic N, Mimica-Dukic N, Dakovic-Svajcer K, Bozin B. Antioxidant and hepatoprotective potential of essential oils of coriander (Coriandrum sativum L.) and caraway (Carum carvi L.) (Apiaceae). J Agric Food Chem. 2010;58(15):8848-53. https://doi.org/10.1021/jf101645n
  26. Tung YT, Yen PL, Lin CY, Chang ST. Anti-inflammatory activities of essential oils and their constituents from different provenances of indigenous cinnamon (Cinnamomum osmophloeum) leaves. Pharm Biol. 2010;48(10):1130-6. https://doi.org/10.3109/13880200903527728
  27. Tung YT, Huang CC, Ho ST, Kuo YH, Lin CC, Lin CT, et al. Bioactive phytochemicals of leaf essential oils of Cinnamomum osmophloeum prevent lipopolysaccharide/D-galactosamine (LPS/D-GalN)-induced acute hepatitis in mice. J Agric Food Chem. 2011;59(15):8117-23. https://doi.org/10.1021/jf2018935
  28. Lima FC, Sousa DF, Ferreira JM, Lima Jr RCP, Tome AR, Cardoso JHL, et al. Croton zehntneri essential oil prevents acetaminophen-induced acute hepatotoxicity in mice. Rec Nat Prod. 2008;2(4):135-40.
  29. Uchida NS, Silva-Filho SE, Aguiar RP, Wiirzler LAM, Cardia GFE, Cavalcante HAO, et al. Protective effect of Cymbopogon citratus essential oil in experimental model of acetaminopheninduced liver injury. Am J Chin Med. 2017;45(3):515-32. https://doi.org/10.1142/s0192415x17500318
  30. Silva MR, Ximenes RM, da Costa JG, Leal LK, de Lopes AA, Viana GS. Comparative anticonvulsant activities of the essential oils (EOs) from Cymbopogon winterianus Jowitt and Cymbopogon citratus (DC) Stapf. in mice. Naunyn Schmiedebergs Arch Pharmacol. 2010;381(5):415-26. https://doi.org/10.1007/s00210-010-0494-9
  31. Ekpenyong CE, Akpan E, Nyoh A. Ethnopharmacology, phytochemistry, and biological activities of Cymbopogon citratus (DC.) Stapf extracts. Chin J Nat Med. 2015;13(5):321-37. https://doi.org/10.1016/S1875-5364(15)30023-6
  32. Albert-Puleo M. Fennel and anise as estrogenic agents. J Ethnopharmacol. 1980;2(4):337-44. https://doi.org/10.1016/s0378-8741(80)81015-4
  33. Ozbek H, Ugras S, Dulger H, Bayram I, Tuncer I, Ozturk G, et al. Hepatoprotective effect of Foeniculum vulgare essential oil. Fitoterapia. 2003;74(3):317-9. https://doi.org/10.1016/S0367-326X(03)00028-5
  34. Ozbek H, Ugras S, Bayram I, Uygan I, Erdogan E, Ozturk A, et al. Hepatoprotective effect of Foeniculum vulgare essential oil: a carbon-tetrachloride induced liver fibrosis model in rats. Scand. J Lab Anim Sci. 2004;31(1):9-17.
  35. do Rego JC, Benkiki N, Chosson E, Kabouche Z, Seguin E, Costentin J. Antidepressant-like effect of hyperfoliatin, a polyisoprenylated phloroglucinol derivative from Hypericum perfoliatum (Clusiaceae) is associated with an inhibition of neuronal monoamines uptake. Eur J Pharmacol. 2007;569(3):197-203. https://doi.org/10.1016/j.ejphar.2007.05.008
  36. Khan AU, Gilani AH, Najeeb-ur-Rehman. Pharmacological studies on Hypericum perforatum fractions and constituents. Pharm Biol. 2011;49(1):46-56. https://doi.org/10.3109/13880209.2010.494307
  37. Suntar IP, Akkol EK, Yilmazer D, Baykal T, Kirmizibekmez H, Alper M, et al. Investigations on the in vivo wound healing potential of Hypericum perforatum L. J Ethnopharmacol. 2010;127(2):468-77. https://doi.org/10.1016/j.jep.2009.10.011
  38. Dadkhah A, Fatemi F, Farsani ME, Roshanaei K, Alipour M, Aligolzadeh H. Hepatoprotective effects of Iranian Hypericum scabrum essential oils against oxidative stress induced by acetaminophen in rats. Braz Arch Biol Technol. 2014;57(3):340-8. https://doi.org/10.1590/S1516-89132014005000012
  39. Brandao MG, Pignal M, Romaniuc S, Grael CF, Fagg CW. Useful Brazilian plants listed in the field books of the French naturalist Auguste de Saint-Hilaire (1779-1853). J Ethnopharmacol. 2012;143(2):488-500. https://doi.org/10.1016/j.jep.2012.06.052
  40. Xu DH, Huang YS, Jiang DQ, Yuan K. The essential oils chemical compositions and antimicrobial, antioxidant activities and toxicity of three Hyptis species. Pharm Biol. 2013;51(9):1125-30. https://doi.org/10.3109/13880209.2013.781195
  41. Lima GC, Vasconcelos YAG, de Santana Souza MT, Oliveira AS, Bomfim RR, de Albuquerque Junior RLC, et al. Hepatoprotective effect of essential oils from hyptis crenata in sepsis-induced liver dysfunction. J Med Food. 2018;21(7):709-15. https://doi.org/10.1089/jmf.2017.0125
  42. Zaghloul SS, Azzam SM, Eid HH, Hassan HA, Sleem AA. Chemical and biological investigation of essential oil of Oroxylum indicum L. Leaves cultivated in Egypt. Int J Pharmacogn Phytochem Res. 2015;7(3):570-5.
  43. Yadav AK, Manika N, Bagchi GD, Gupta MM. Simultaneous determination of flavonoids in Oroxylum indicum by RP-HPLC. Med Chem Res. 2013;22(5):2222-7. https://doi.org/10.1007/s00044-012-0214-8
  44. Ali M, Chaudhary A, Ramachandran R. New pterocarpans from Oroxylum indicum stem bark. Indian J Chem. 1999;38B:950-2.
  45. Pourgholami MH, Majzoob S, Javadi M, Kamalinejad M, Fanaee GH, Sayyah M. The fruit essential oil of Pimpinella anisum exerts anticonvulsant effects in mice. J Ethnopharmacol. 1999;66(2):211-5. https://doi.org/10.1016/S0378-8741(98)00161-5
  46. Tabanca N, Ma G, Pasco DS, Bedir E, Kirimer N, Baser KH, et al. Effect of essential oils and isolated compounds from Pimpinella species on NF-kappaB: a target for antiinflammatory therapy. Phytother Res. 2007;21(8):741-5. https://doi.org/10.1002/ptr.2154
  47. Andarwulan N, Shetty K. Phenolic content in differentiated tissue cultures of untransformed and Agrobacterium-transformed roots of anise (Pimpinella anisum L.). J Agric Food Chem. 1999;47(4):1776-80. https://doi.org/10.1021/jf981214r
  48. Jamshidzadeh A, Heidari R, Razmjou M, Karimi F, Moein MR, Farshad O, et al. An in vivo and in vitro investigation on hepatoprotective effects of Pimpinella anisum seed essential oil and extracts against carbon tetrachloride-induced toxicity. Iran J Basic Med Sci. 2015;18(2):205-11.
  49. Rajopadhye AA, Upadhye AS, Dandge CN, Naik DG. Essential oil from leaf galls on Pistacia chinensis ssp. integerrima: chemical composition, in vitro and in vivo antioxidant and hepatoprotective activity. J Essent Oil Bear Plants. 2016;19(7):1648-59. https://doi.org/10.1080/0972060X.2016.1174079
  50. Ramachandra YL, Shankara BER, Ganapathy PSS, Sundar SR. In-vitro antimicrobial activity of Pistacia integerrima leaf gall extracts. Pharmacophore. 2010;1(2):149-54.
  51. Ahmad NS, Waheed A, Farman M, Qayyum A. Analgesic and anti-inflammatory effects of Pistacia integerrima extracts in mice. J Ethnopharmacol. 2010;129(2):250-3. https://doi.org/10.1016/j.jep.2010.03.017
  52. Sanguinetti M, Posteraro B, Romano L, Battaglia F, Lopizzo T, De Carolis E, et al. In vitro activity of Citrus bergamia (bergamot) oil against clinical isolates of dermatophytes. J Antimicrob Chemother. 2007;59(2):305-8. https://doi.org/10.1093/jac/dkl473
  53. Rasooli A, Fatemi F, Akbarzadeh K, Dini S, Bahremand S. Synergistic protective activity of deuterium depleted water (DDW) and Satureja rechingeri essential oil on hepatic oxidative injuries induced by acetaminophen in rats. J Essent Oil Bear Plants. 2016;19(5):1086-101. https://doi.org/10.1080/0972060X.2015.1111776
  54. Bezic N, Samanic I, Dunkic V, Besendorfer V, Puizina J. Essential oil composition and internal transcribed spacer (ITS) sequence variability of four South-Croatian Satureja species (Lamiaceae). Molecules. 2009;14(3):925-38. https://doi.org/10.3390/molecules14030925
  55. Sonboli A, Fakhari A, Kanani MR, Yousefzadi M. Antimicrobial activity, essential oil composition and micromorphology of trichomes of Satureja laxiflora C. Koch from Iran. Z Naturforsch C J Biosci. 2004;59(11-12):777-81. https://doi.org/10.1515/znc-2004-11-1202
  56. Kandil O, Radwan NM, Hassan AB, Amer AM, el-Banna HA, Amer WM. Extracts and fractions of Thymus capitatus exhibit antimicrobial activities. J Ethnopharmacol. 1994;44(1):19-24. https://doi.org/10.1016/0378-8741(94)90094-9
  57. Dob T, Dahmane D, Benabdelkader T, Chelghoum C. Studies on the essential oil composition and antimicrobial activity of Thymus algeriensis Boiss. et Reut. Int J Aromather. 2006;16(2):95-100. https://doi.org/10.1016/j.ijat.2006.04.003
  58. Van den Broucke CO, Lemli JA. Pharmacological and chemical investigation of thyme liquid extracts. Planta Med. 1981;41(2):129-35. https://doi.org/10.1055/s-2007-971689
  59. Dapkevicius A, van Beek TA, Lelyveld GP, van Veldhuizen A, de Groot A, Linssen JP, et al. Isolation and structure elucidation of radical scavengers from Thymus vulgaris leaves. J Nat Prod. 2002;65(6):892-6. https://doi.org/10.1021/np010636j
  60. Vutyavanich T, Kraisarin T, Ruangsri R. Ginger for nausea and vomiting in pregnancy: randomized, double-masked, placebocontrolled trial. Obstet Gynecol. 2001;97(4):577-82. https://doi.org/10.1016/S0029-7844(00)01228-X
  61. Fuhrman B, Rosenblat M, Hayek T, Coleman R, Aviram M. Ginger extract consumption reduces plasma cholesterol, inhibits LDL oxidation and attenuates development of atherosclerosis in atherosclerotic, apolipoprotein E-deficient mice. J Nutr. 2000;130(5):1124-31. https://doi.org/10.1093/jn/130.5.1124
  62. Choudhury D, Das A, Bhattacharya A, Chakrabarti G. Aqueous extract of ginger shows antiproliferative activity through disruption of microtubule network of cancer cells. Food Chem Toxicol. 2010;48(10):2872-80. https://doi.org/10.1016/j.fct.2010.07.020
  63. Liu CT, Raghu R, Lin SH, Wang SY, Kuo CH, Tseng YJ, et al. Metabolomics of ginger essential oil against alcoholic fatty liver in mice. J Agric Food Chem. 2013;61(46):11231-40. https://doi.org/10.1021/jf403523g
  64. Matsuda A, Wang Z, Takahashi S, Tokuda T, Miura N, Hasegawa J. Upregulation of mRNA of retinoid binding protein and fatty acid binding protein by cholesterol enriched-diet and effect of ginger on lipid metabolism. Life Sci. 2009;84(25-26):903-7. https://doi.org/10.1016/j.lfs.2009.04.004
  65. Li Y, Tran VH, Duke CC, Roufogalis BD. Preventive and protective properties of Zingiber officinale (Ginger) in diabetes mellitus, diabetic complications, and associated lipid and other metabolic disorders: a brief review. Evid Based Complement Alternat Med. 2012;2012:516870.
  66. Nakamura Y, Miyamoto M, Murakami A, Ohigashi H, Osawa T, Uchida K. A phase II detoxification enzyme inducer from lemongrass: identification of citral and involvement of electrophilic reaction in the enzyme induction. Biochem Biophys Res Commun. 2003;302(3):593-600. https://doi.org/10.1016/S0006-291X(03)00219-5
  67. Xia H, Liang W, Song Q, Chen X, Chen X, Hong J. The in vitro study of apoptosis in NB4 cell induced by citral. Cytotechnology. 2013;65(1):49-57. https://doi.org/10.1007/s10616-012-9453-2
  68. Lai YS, Lee WC, Lin YE, Ho CT, Lu KH, Lin SH, et al. Ginger essential oil ameliorates hepatic injury and lipid accumulation in high fat diet-induced nonalcoholic fatty liver disease. J Agric Food Chem. 2016;64(10):2062-71. https://doi.org/10.1021/acs.jafc.5b06159
  69. Washington MK. Autoimmune liver disease: overlap and outliers. Mod Pathol. 2007;20 Suppl 1:S15-30. https://doi.org/10.1038/modpathol.3800684
  70. Qian T, Herman B, Lemasters JJ. The mitochondrial permeability transition mediates both necrotic and apoptotic death of hepatocytes exposed to Br-A23187. Toxicol Appl Pharmacol. 1999;154(2):117-25. https://doi.org/10.1006/taap.1998.8580
  71. Kon K, Kim JS, Jaeschke H, Lemasters JJ. Mitochondrial permeability transition in acetaminophen-induced necrosis and apoptosis of cultured mouse hepatocytes. Hepatology. 2004;40(5):1170-9. https://doi.org/10.1002/hep.20437
  72. Santos FA, Rao VS. 1,8-cineol, a food flavoring agent, prevents ethanol-induced gastric injury in rats. Dig Dis Sci. 2001;46(2):331-7. https://doi.org/10.1023/A:1005604932760
  73. Santos FA, Rao VS. Antiinflammatory and antinociceptive effects of 1,8-cineole a terpenoid oxide present in many plant essential oils. Phytother Res. 2000;14(4):240-4. https://doi.org/10.1002/1099-1573(200006)14:4<240::AID-PTR573>3.0.CO;2-X
  74. Juergens UR, Stober M, Vetter H. Inhibition of cytokine production and arachidonic acid metabolism by eucalyptol (1.8-cineole) in human blood monocytes in vitro. Eur J Med Res. 1998;3(11):508-10.
  75. Aristatile B, Al-Numair KS, Veeramani C, Pugalendi KV. Effect of carvacrol on hepatic marker enzymes and antioxidant status in D-galactosamine-induced hepatotoxicity in rats. Fundam Clin Pharmacol. 2009;23(6):757-65. https://doi.org/10.1111/j.1472-8206.2009.00721.x
  76. Yanishlieva NV, Marinova EM, Gordon MH, Raneva VG. Antioxidant activity and mechanism of action of thymol and carvacrol in two lipid systems. Food Chem. 1999;64(1):59-66. https://doi.org/10.1016/S0308-8146(98)00086-7
  77. Hajhashemi V, Ghannadi A, Pezeshkian SK. Antinociceptive and anti-inflammatory effects of Satureja hortensis L. extracts and essential oil. J Ethnopharmacol. 2002;82(2-3):83-7. https://doi.org/10.1016/S0378-8741(02)00137-X
  78. Shelef LA. Antimicrobial effects of spices. J Food Saf. 1984;6(1):29-44. https://doi.org/10.1111/j.1745-4565.1984.tb00477.x
  79. Sokmen M, Serkedjieva J, Daferera D, Gulluce M, Polissiou M, Tepe B, et al. In vitro antioxidant, antimicrobial, and antiviral activities of the essential oil and various extracts from herbal parts and callus cultures of Origanum acutidens. J Agric Food Chem. 2004;52(11):3309-12. https://doi.org/10.1021/jf049859g
  80. Evangelou A, Kalpouzos G, Karkabounas S, Liasko R, Nonni A, Stefanou D, et al. Dose-related preventive and therapeutic effects of antioxidants-anticarcinogens on experimentally induced malignant tumors in Wistar rats. Cancer Lett. 1997;115(1):105-11. https://doi.org/10.1016/S0304-3835(97)04712-5
  81. Alam K, Nagi MN, Badary OA, Al-Shabanah OA, Al-Rikabi AC, Al-Bekairi AM. The protective action of thymol against carbon tetrachloride hepatotoxicity in mice. Pharmacol Res. 1999;40(2):159-63. https://doi.org/10.1006/phrs.1999.0472