Abstract
Plant secondary metabolites have received a lot of attention for their immense pharmacological activities and low side effects. Monoterpenes, belonging to the terpene family, are one such class of naturally occurring plant secondary metabolites that exhibit diverse pharmacological properties including anticancer, antidiabetic, hepatoprotective, and antioxidant properties. Carvacrol, a monoterpenic phenol found in volatile oils of plants, has a wide spectrum of pharmacological activities and is therefore considered to be a valuable therapeutic agent. Through this review, recent advances in the pharmacological properties of carvacrol and possible molecular mechanisms involved are described.
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References
Ahmad A, Ansari IA (2021) Carvacrol exhibits chemopreventive potential against cervical cancer cells via caspase-dependent apoptosis and abrogation of cell cycle progression. Anticancer Agents Med Chem 21:2224–2235. https://doi.org/10.2174/1871520621999201230201258
Ahmad A, Khan A, Akhtar F, Yousuf S, Xess I, Khan LA, Manzoor N (2011) Fungicidal activity of thymol and carvacrol by disrupting ergosterol biosynthesis and membrane integrity against Candida. Eur J Clin Microbiol Infect Dis 30:41–50. https://doi.org/10.1007/s10096-010-1050-8
Alagawany M, El-Hack M, Farag M, Tiwari R, Dhama K (2015) Biological effects and modes of action of carvacrol in animal and poultry production and health - a review. Adv Animal Vet Sci 3:73–84. https://doi.org/10.14737/journal.aavs/2015/3.2s.73.84
Alers S, Löffler AS, Wesselborg S, Stork B (2012) Role of AMPK-mTOR-Ulk1/2 in the regulation of autophagy: cross talk, shortcuts, and feedbacks. Mol Cell Biol 32:2–11. https://doi.org/10.1128/MCB.06159-11
Aljelehawy Q, Maroufi Y, Javid H, Mohammadi MR, Allah RM, Taheri OSV, Mohammadzade H (2023) Anticancer, antineurodegenerative, antimicrobial, and antidiabetic activities of carvacrol: recent advances and limitations for effective formulations. Nano Micro Biosystems 2:1–10. https://doi.org/10.22034/nmbj.2023.380207.1009
Andersen A (2006) Final report on the safety assessment of sodium p-chloro-m-cresol, p-chloro-m-cresol, chlorothymol, mixed cresols, m-cresol, o-cresol, p-cresol, isopropyl cresols, thymol, o-cymen-5-ol, and carvacrol. Int J Toxicol 25(Suppl 1):29–127. https://doi.org/10.1080/10915810600716653
Anderson JA, Coats J (2012) Acetylcholinesterase inhibition by nootkatone and carvacrol in arthropods. Pestic Biochem Phys 102:124–128. https://doi.org/10.1016/j.pestbp.2011.12.002
Arigesavan K, Sudhandiran G (2015) Carvacrol exhibits anti-oxidant and anti-inflammatory effects against 1,2-dimethyl hydrazine plus dextran sodium sulfate induced inflammation associated carcinogenicity in the colon of Fischer 344 rats. Biochem Biophys Res Commun 461:314–320. https://doi.org/10.1016/j.bbrc.2015.04.030
Aristatile B, Al Numair KS, Veeramani C, Pugalendi KV (2009) Effect of carvacrol on hepatic marker enzymes and antioxidant status in D-galactosamine-induced hepatotoxicity in rats. Fundam Clin Pharmacol 23:757–765. https://doi.org/10.1111/j.1472-8206.2009.00721.x
Austgulen LT, Solheim E, Schelin RR (1987) Metabolism in rats of p-cymene derivatives: carvacrol and thymol. Pharmacol Toxicol 61:98–102. https://doi.org/10.1111/j.1600-0773.1987.tb01783.x
Awuchi C (2019) The biochemistry, toxicology, and uses of the pharmacologically active phytochemicals: alkaloids, terpenes, polyphenols, and glycosides. J Food Pharm Sci 7:131–150. https://doi.org/10.22146/jfps.666
Bakır M, Geyikoglu F, Colak S, Turkez H, Bakır TO, Hosseinigouzdagani M (2016) The carvacrol ameliorates acute pancreatitis-induced liver injury via antioxidant response. Cytotechnology 68:1131–1146. https://doi.org/10.1007/s10616-015-9871-z
Baluchnejadmojarad T, Hassanshahi J, Roghani M, Raoufi S (2014) Protective effect of carvacrol in 6-hydroxydopamine hemi-parkinsonian rat model. J Basic Clin Pathophysiol 2:29–34
Barnwal P, Vafa A, Afzal S, Shahid A, Hasan SK, Alpashree N, Sultana S (2018) Benzo(a)pyrene induces lung toxicity and inflammation in mice: prevention by carvacrol. Hum Exp Toxicol 37:752–761. https://doi.org/10.1177/0960327117735572
Batool A, Majeed ST, Aashaq S, Majeed R, Shah G, Nazir N, Andrabi KI (2019) Eukaryotic initiation factor 4E (eIF4E) sequestration mediates 4E-BP1 response to rapamycin. Int J Biol Macromol 125:651–659. https://doi.org/10.1016/j.ijbiomac.2018.12.102
Batool A, Majeed ST, Aashaq S, Majeed R, Bhat NN, Andrabi KI (2020) Eukaryotic initiation factor 4E is a novel effector of mTORC1 signaling pathway in cross talk with Mnk1. Mol Cell Biochem 465:13–26. https://doi.org/10.1007/s11010-019-03663-z
Beigh MA, Showkat M, Ul Hussain M, Latoo SA, Majeed ST, Andrabi KI (2012) Rapamycin inhibition of baculovirus recombinant (BVr) ribosomal protein S6 kinase (S6K1) is mediated by an event other than phosphorylation. Cell Commun Signal 10:4. https://doi.org/10.1186/1478-811X-10-4
Bose S, Mali J, Mandal SC (2020) Application of phytochemicals in pharmaceuticals, in: Patra JK, Shukla AC, Das G (Eds.), Advances in pharmaceutical biotechnology: recent progress and future applications. Springer, Singapore. 55–68. https://doi.org/10.1007/978-981-15-2195-9_5
Cacciatore I, Di Giulio M, Fornasari E, Di Stefano A, Cerasa LS, Marinelli L, Turkez H, Di Campli E, Di Bartolomeo S, Robuff I, Cellini L (2015) Carvacrol codrugs: a new approach in the antimicrobial plan. PLoS One 10:e0120937. https://doi.org/10.1371/journal.pone.0120937
Carvalho FO, Silva ÉR, Gomes IA, Santana HSR, Nascimento Santos D, Oliveira Souza GP, Jesus Silva D, Monteiro JCM, Albuquerque Júnior RL, Souza Araújo AA, Nunes PS (2020a) Anti-inflammatory and antioxidant activity of carvacrol in the respiratory system: a systematic review and meta-analysis. Phytother Res 34:2214–2229. https://doi.org/10.1002/ptr.6688
CavalcanteMelo FH, Rios ERV, Rocha NFM, de CitóMdo CO, Fernandes ML, de Sousa DP, de Vasconcelos SMM, de Sousa FCF (2012) Antinociceptive activity of carvacrol (5-isopropyl-2-methylphenol) in mice. J Pharm Pharmacol 64:1722–1729. https://doi.org/10.1111/j.2042-7158.2012.01552.x
Chagas CM, Moss S, Alisaraie (2018) Drug metabolites and their effects on the development of adverse reactions: revisiting Lipinski’s Rule of Five. Int J Pharm 549:133–149. https://doi.org/10.1016/j.ijpharm.2018.07.046
Chaillot J, Tebbji R, Boone C, Brown GW, Bellaoui M, Sellam A (2015) The monoterpene carvacrol generates endoplasmic eeticulum stress in the pathogenic fungus Candida albicans. Antimicrob Agents Chemother 59:4584–4592. https://doi.org/10.1128/AAC.00551-15
Chen H, Fon SY (2022) Carvacrol induces apoptosis in human breast cancer cells via Bcl-2/CytC signaling pathway (preprint). In Review. https://doi.org/10.21203/rs.3.rs-2105532/v1
Cox-Georgian D, Ramadoss N, Dona C, Basu C (2019) Therapeutic and medicinal uses of terpenes, in: Joshee N, Dhekney SA, Parajuli P (Eds.), Medicinal plants: from farm to pharmacy. Springer International Publishing, Cham, 333–359. https://doi.org/10.1007/978-3-030-31269-5_15
Dai W, Sun C, Huang S, Zhou Q (2016a) Carvacrol suppresses proliferation and invasion in human oral squamous cell carcinoma. Onco Targets Ther 9:2297–2304. https://doi.org/10.2147/OTT.S98875
Dai W, Sun C, Huang S, Zhou Q (2016b) Carvacrol suppresses proliferation and invasion in human oral squamous cell carcinoma. Oncotargets Ther 9:2297–2304. https://doi.org/10.2147/OTT.S98875
de Carvalho FO, Silva ÉR, Gomes IA, Santan SR, do Nascimento Santos, D, de Oliveira Souza GP, de Jesus Silva, D, Monteir JCM, de Albuquerque Júnior, RLC, de Souza Araújo AA, Nunes PS (2020b) Anti-inflammatory and antioxidant activity of carvacrol in the respiratory system: a systematic review and meta-analysis. Phytother Res 34:2214–2229. https://doi.org/10.1002/ptr.6688
De Oliveira AS, De Oliveira AS (2020) Carvacrol: a brief analysis of molecular properties and their therapeutic potential. AJMC. https://doi.org/10.31487/j.AJMC.2020.01.10
De Vincenzi M, Stammati A, De Vincenzi A, Silan M (2004) Constituents of aromatic plants: carvacrol. Fitoterapia 75:801–804. https://doi.org/10.1016/j.fitote.2004.05.002
Dong RH, Fang ZZ, Zhu LL, Ge GB, Yang L, Liu ZY (2012) Identification of UDP-glucuronosyltransferase isoforms involved in hepatic and intestinal glucuronidation of phytochemical carvacrol. Xenobiotica 42:1009–1016. https://doi.org/10.3109/00498254.2012.682614
Egan WJ, Merz KM, Baldwin JJ (2000) Prediction of drug absorption using multivariate statistics. J Med Chem 43:3867–3877. https://doi.org/10.1021/jm000292e
Ekor M (2014) The growing use of herbal medicines: issues relating to adverse reactions and challenges in monitoring safety. Front Pharmacol 4:177. https://doi.org/10.3389/fphar.2013.00177
Ezhumalai M, Radhiga T, Pugalendi KV (2014) Antihyperglycemic effect of carvacrol in combination with rosiglitazone in high-fat diet-induced type 2 diabetic C57BL/6J mice. Mol Cell Biochem 385:23–31. https://doi.org/10.1007/s11010-013-1810-8
FachiniQueiroz FC, Kummer R, Estevão Silva CF, de Carvalho MDB, Cunha JM, Grespan R, Bersani Amado CA, Cuman RKN (2012) Effects of yhymol and carvacrol, constituents of Thymus vulgaris L essential oil, on the inflammatory response. Evid-Based Compl Alt Med 2012:e657026. https://doi.org/10.1155/2012/657026
Fan K, Li X, Cao Y, Qi H, Li L, Zhan Q, Sun H (2015) Carvacrol inhibits proliferation and induces apoptosis in human colon cancer cells. Anticancer Drugs 26:813–823. https://doi.org/10.1097/CAD.0000000000000263
Ferlay J, Colombet M, Soerjomataram I, Mathers C, Dm P, Znaor PM, Bray AF (2019) Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods. Int J Cancer 144:1941–1953. https://doi.org/10.1002/ijc.31937
Guimarães AG, Xavier MA, De Santana MT, Camargo EA, Santos CA, Brito FA, Barreto EO, Cavalcanti SCH, Antoniolli ÂR, Oliveira RCM, Quintans Júnior LJ (2012) Carvacrol attenuates mechanical hypernociception and inflammatory response. Naunyn-Schmiedeberg’s Arch Pharmacol 385:253–263. https://doi.org/10.1007/s00210-011-0715-x
Guimarães AG, Oliveira MA Alves, R dos S, Menezes, P dos P, Serafini MR, Araújo, AA de S, Bezerra DP, Quintans Júnior LJ (2015) Encapsulation of carvacrol, a monoterpene present in the essential oil of oregano, with β-cyclodextrin, improves the pharmacological response on cancer pain experimental protocols. Chem Biol Interact 227:69–76https://doi.org/10.1016/j.cbi.2014.12.020
Haddadi H, Rajaei Z, Alaei H, Shahidani S (2018) Chronic treatment with carvacrol improves passive avoidance memory in a rat model of Parkinson’s disease. Arq Neuropsiquiatr 76:71–77. https://doi.org/10.1590/0004-282X20170193
Hardy K (2021) Paleomedicine and the evolutionary context of medicinal plant use. Rev Bras Farmacogn 31:1–15. https://doi.org/10.1007/s43450-020-00107-4
Heidarian E, Keloushadi M (2019) Antiproliferative and anti-invasion effects of carvacrol on PC3 human prostate cancer cells through reducing pSTAT3, pAKT, and pERK1/2 signaling proteins. Int J Prev Med 10:156. https://doi.org/10.4103/ijpvm.IJPVM_292_17
Herrera Calderon O, Yepes Pérez AF, Quintero Saumeth J, RojasArmas JP, Palomino Pacheco M, Ortiz Sánchez JM, Cieza Macedo EC, Arroyo Acevedo JL, Figueroa Salvador L, Peña-Rojas G, Andía-Ayme V (2020) Carvacrol: an in silico approach of a candidate drug on HER2, PI3Kα, mTOR, hER-α, PR, and EGFR receptors in the breast cancer. Evid Based Compl Alt Med 2020:8830665. https://doi.org/10.1155/2020/8830665
Hotta M, Nakata R, Katsukawa M, Hori K, Takahashi S, Inoue H (2010) Carvacrol, a component of thyme oil, activates PPARα and γ and suppresses COX-2 expression. J Lipid Res 51:132–139. https://doi.org/10.1194/jlr.M900255-JLR200
Imran M, Aslam M, Alsagaby SA, Saeed F, Ahmad I, Afzaal M, Arshad MU, Abdelgawad MA, El Ghorab AH, Khames A, Shariati MA, Ahmad A, Hussain M, Imran A, Islam S (2022) Therapeutic application of carvacrol: a comprehensive review. Food Sci Nutr 10:3544–3561. https://doi.org/10.1002/fsn3.2994
Jukic M, Politeo O, Maksimovic M, Mia M, Mladen M (2007) In vitro acetylcholinesterase inhibitory properties of thymol, carvacrol and their derivatives thymoquinone and thymohydroquinone. Phytother Res 21:259–261. https://doi.org/10.1002/ptr.2063
Khan I, Bahuguna A, Kumar P, BajpaiVK KSC (2018) In vitro and in vivo antitumor potential of carvacrol nanoemulsion against human lung adenocarcinoma A549 cells via mitochondrial mediated apoptosis. Sci Rep 8:144. https://doi.org/10.1038/s41598-017-18644-9
Khazdair MR, Boskabady MH (2019) A double-blind, randomized, placebo-controlled clinical trial on the effect of carvacrol on serum cytokine levels and pulmonary function tests in sulfur mustard induced lung injury. Cytokine 113:311–318. https://doi.org/10.1016/j.cyto.2018.07.031
Khazir J, Mir B, Mir SA, Cowan D (2013) Natural products as lead compounds in drug discovery. J Asian Nat Prod Res 15:764–788. https://doi.org/10.1080/10286020.2013.798314
Krause ST, Liao P, Crocoll C, Boachon B, Förster C, Leidecker F, Wiese N, Zhao D, Wood JC, Buell CR, Gershenzon J, Dudareva N, Degenhard J (2021) The biosynthesis of thymol, carvacrol, and thymohydroquinone in Lamiaceae proceeds via cytochrome P450s and a short-chain dehydrogenase. P Natl Acad Sci 118:e2110092118. https://doi.org/10.1073/pnas.2110092118
Kurt BZ, Gazioglu I, Dag A, Salmas RE, Kayık G, Durdagi S, Sonmez F (2017) Synthesis, anticholinesterase activity and molecular modeling study of novel carbamate-substituted thymol/carvacrol derivatives. Bioorgan Med Chem 25:1352–1363. https://doi.org/10.1016/j.bmc.2016.12.037
Lee Y, Ding P (2016) Physiological production of essential oil in plants - ontogeny, secretory structures and seasonal variations: review. Pertanika J Scholarly Res Rev 2:1–11
Li Y, Mai Y, Qiu X, Chen X, Li C, Yuan W, Hou N (2020) Effect of long-term treatment of carvacrol on glucose metabolism in streptozotocin-induced diabetic mice. BMC Complement Med Ther 20:142. https://doi.org/10.1186/s12906-020-02937-0
Liao P, Hemmerlin A, Bach TJ, Chye M-L (2016) The potential of the mevalonate pathway for enhanced isoprenoid production. Biotechnol Adv 34:697–713. https://doi.org/10.1016/j.biotechadv.2016.03.005
Lima IO, Pereira FDO, Oliveir WAD, Lima EDO, Menezes EA, Cunha FA, Diniz DFFM (2013) Antifungal activity and mode of action of carvacrol against Candida albicans strains. J Essent Oil Res 25:138–142. https://doi.org/10.1080/10412905.2012.754728
Lins LCRF, Souza MF, Bispo JMM, Gois AM, Melo TCS, Andrade RAS, Quintans Junior LJ, Ribeiro AM, Silva RH, Santos JR, Marchioro M (2018) Carvacrol prevents impairments in motor and neurochemical parameters in a model of progressive parkinsonism induced by reserpine. Brain Res Bull 139:9–15. https://doi.org/10.1016/j.brainresbull.2018.01.017
Llana Ruiz Cabello M, Maisanaba S, Puerto M, Prieto AI, Pichardo S, Moyano R, González Pérez JA, Cameán AM (2016) Genotoxicity evaluation of carvacrol in rats using a combined micronucleus and comet assay. Food Chem Toxicol 98:240–250. https://doi.org/10.1016/j.fct.2016.11.005
Magi G, Marini E, Facinelli B (2015) Antimicrobial activity of essential oils and carvacrol, and synergy of carvacrol and erythromycin, against clinical, erythromycin-resistant Group A Streptococci. Front Microbiol 6:165. https://doi.org/10.3389/fmicb.2015.00165
Majeed ST, Batool A, Majeed R, Bhat NN, Zargar MA, Andrabi KI (2021) mTORC1 induces eukaryotic translation initiation factor 4E interaction with TOS-S6 kinase 1 and its activation. Cell Cycle 20:839–854. https://doi.org/10.1080/15384101.2021.1901038
Majeed ST, Majeed R, Andrabi KI (2022) Expanding the view of the molecular mechanisms of autophagy pathway. J Cell Physiol 237:3257–3277. https://doi.org/10.1002/jcp.30819
Majeed ST, Majeed R, Malik AA, Andrabi KI (2023) MTORC2 is a physiological hydrophobic motif kinase of S6 Kinase 1. Biochim Biophys Acta Mol Cell Res 1870:119449. https://doi.org/10.1016/j.bbamcr.2023.119449
Majeed ST, Majeed R, Shah G, Andrabi KI (2018) S6 Kinase: a compelling prospect for therapeutic interventions, in: Homeostasis - An Integrated Vision. IntechOpen. https://doi.org/10.5772/intechopen.75209
Manouchehrabadi M, Farhadi M, Azizi Z, Torkaman Boutorabi A (2020) Carvacrol protects against 6-hydroxydopamine-induced neurotoxicity in in vivo and in vitro models of Parkinson’s disease. Neurotox Res 37:156–170. https://doi.org/10.1007/s12640-019-00088-w
Melo FHC, Venâncio ET, De Sousa DP, De França Fonteles MM, De Vasconcelos SMM, Viana GSB, De Sousa FCF (2010) Anxiolytic-like effect of carvacrol (5-isopropyl-2-methylphenol) in mice: involvement with GABAergic transmission. Fund Clin Pharmacol 24:437–443. https://doi.org/10.1111/j.1472-8206.2009.00788.x
Melo FHC, Moura BA, De Sousa DP, De Vasconcelos SMM, Macedo DS, Fonteles MMDF, Viana GSDB, De Sousa FCF (2011) Antidepressant-like effect of carvacrol (5-Isopropyl-2-methylphenol) in mice: involvement of dopaminergic system: involvement of dopaminergic system. Fund Clin Pharmacol 25:362–367. https://doi.org/10.1111/j.1472-8206.2010.00850.x
Memar MY, Raei P, Alizadeh N, Akbari Aghdam M, Kafil HS (2017) Carvacrol and thymol: strong antimicrobial agents against resistant isolates. Rev Med Microbiol 28:63–68. https://doi.org/10.1097/MRM.0000000000000100
Mondal A, Bose S, Mazumder K, Khanra R (2021) Carvacrol (Origanum vulgare): therapeutic properties and molecular mechanisms, in: Pal D, Nayak AK (eds.), Bioactive natural products for pharmaceutical applications, advanced structured materials. Springer International Publishing, Cham. 437–462. https://doi.org/10.1007/978-3-030-54027-2_13
Nostro A, Papalia T (2012) Antimicrobial activity of carvacrol: current progress and future prospectives. Recent Pat Antiinfect Drug Discov 7:28–35. https://doi.org/10.2174/157489112799829684
Palabiyik SS, Karakus E, Halici Z, Cadirci E, Bayir Y, Ayaz G, Cinar I (2016) The protective effects of carvacrol and thymol against paracetamol-induced toxicity on human hepatocellular carcinoma cell lines (HepG2). Hum Exp Toxicol 35:1252–1263. https://doi.org/10.1177/0960327115627688
Parnas M, Peters M, Dadon D, Lev S, Vertkin I, Slutsky I, Minke B (2009) Carvacrol is a novel inhibitor of Drosophila TRPL and mammalian TRPM7 channels. Cell Calcium 45:300–309. https://doi.org/10.1016/j.ceca.2008.11.009
Parvin R, Shahrokh KO, Mozafar S, Hassan E, Mehrdad B (2014) Biosynthesis, regulation and properties of plant monoterpenoids. J Med Plants Res 8:983–991. https://doi.org/10.5897/JMPR2012.387
Potočnjak I, Gobin I, Domitrović R (2018) Carvacrol induces cytotoxicity in human cervical cancer cells but causes cisplatin resistance: involvement of MEK-ERK activation. Phytother Res 32:1090–1097. https://doi.org/10.1002/ptr.6048
Poulain D (2015) Candida albicans, plasticity and pathogenesis. Crit Rev Microbiol 41:208–217. https://doi.org/10.3109/1040841X.2013.813904
Rašković AL, Kvrgić MP, Tomas AD, Stilinović NP, Čabarkapa VS, StojšićMilosavljević AÐ, Kusturica MNP, Rakić DB (2020) Antinociceptive activity of thyme (Thymus vulgaris L.) and interactions with neurotropics and analgesics. Braz J Pharm Sci 56:e18819. https://doi.org/10.1590/s2175-97902020000318819
Rehman R, Hanif MA, Mushtaq Z, Al Sadi AM (2016) Biosynthesis of essential oils in aromatic plants: a review. Food Rev Int 32:117–160. https://doi.org/10.1080/87559129.2015.1057841
Reiner GN, Labuckas DO, García DA (2009) Lipophilicity of some GABAergic phenols and related compounds determined by HPLC and partition coefficients in different systems. J Pharm Biomed Anal 49:686–691. https://doi.org/10.1016/j.jpba.2008.12.040
Salehi B, Azzini E, Zucca P, Mariavaroni E, V Anil Kumar N, Dini L, Panzarini E, Rajkovic J, Valere Tsouh Fokou P, Peluso I, Prakash Mishra A, Nigam M, El Rayess Y, El Beyrouthy M, NW Setzer, Polito L, Iriti M, Sureda A, Magdalena Quetglas-Llabrés M, Martorell M, Martins N, Sharifi-Rad M, M Estevinho L, Sharifi-Rad J (2020) Plant-derived bioactives and oxidative stress-related disorders: a key trend towards healthy aging and longevity promotion. Appl Sci 10:947. https://doi.org/10.3390/app10030947
Sampaio LA, Pina LTS, Serafini MR, Tavares DDS, Guimarães AG (2021) Antitumor effects of carvacrol and thymol: a systematic review. Front Pharmacol 12:702487. https://doi.org/10.3389/fphar.2021.702487
Schwab W, Fischer T, Wüst M (2015) Terpene glucoside production: improved biocatalytic processes using glycosyltransferases. Eng Life Sci 15:376–386. https://doi.org/10.1002/elsc.201400156
Sharifi Rad M, Varoni EM, Iriti M, Martorell M, del Setzer WN, Mar Contreras M, Salehi B, Solta Nejad A, Rajabi S, Tajbakhsh M, Sharifi Rad J (2018) Carvacrol and human health: a comprehensive review. Phytother Res 32:1675–1687. https://doi.org/10.1002/ptr.6103
Silva JC, Almeida JRGS, Quintans JSS, Gopalsamy RG, Shanmugam S, Serafini MR, Oliveira MRC, Silva BAF, Martins AOBPB, Castro FF, Menezes IRA, Coutinho HDM, Oliveira RCM, Thangaraj P, Araújo AAS, Quintans Júnior LJ (2016) Enhancement of orofacial antinociceptive effect of carvacrol, a monoterpene present in oregano and thyme oils, by β-cyclodextrin inclusion complex in mice. Biomed Pharmacother 84:454–461. https://doi.org/10.1016/j.biopha.2016.09.065
Somensi N, Rabelo TK, Guimarães AG, Quintans-Junior LJ, de Souza Araújo AA, Moreira JCF, Gelain DP (2019) Carvacrol suppresses LPS-induced pro-inflammatory activation in RAW 264.7 macrophages through ERK1/2 and NF-kB pathway. Int Immunopharmacol 75:105743. https://doi.org/10.1016/j.intimp.2019.105743
Suntres ZE, Coccimiglio J, Alipour M (2015) The bioactivity and toxicological actions of carvacrol. Crit Rev Food Sci Nutr 55:304–318. https://doi.org/10.1080/10408398.2011.653458
Talapatra SK, Talapatra B (2015) Chemistry of plant natural products: stereochemistry, conformation, synthesis, biology, and medicine. Springer, Berlin Heidelberg, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-45410-3
Tiefensee Ribeiro C, Gasparotto J, Petiz LL, Brum PO, Peixoto DO, Kunzler A, da Rosa Silva HT, Bortolin RC, Almeida RF, Quintans-Junior LJ, Araújo AA, Moreira JCF, Gelain DP (2019) Oral administration of carvacrol/β-cyclodextrin complex protects against 6-hydroxydopamine-induced dopaminergic denervation. Neurochem Int 126:27–35. https://doi.org/10.1016/j.neuint.2019.02.021
Ultee A, Bennik MHJ, Moezelaar R (2002) The phenolic hydroxyl group of carvacrol is essential for action against the food-borne pathogen Bacillus cereus. Appl Environ Microbiol 68:1561–1568. https://doi.org/10.1128/AEM.68.4.1561-1568.2002
Veber DF, Johnson SR, Cheng HY, Smith BR, Ward KW, Kopple KD (2002) Molecular properties that influence the oral bioavailability of drug candidates. J Med Chem 45:2615–2623. https://doi.org/10.1021/jm020017n
Vilmosh N, Delev D, Kostadinov I, Zlatanova H, Kotetarova M, Kandilarov I, Kostadinova I (2022) Anxiolytic effect of Satureja montana dry extract and its active compounds rosmarinic acid and carvacrol in acute stress experimental model. J Integr Neurosci 21:124. https://doi.org/10.31083/j.jin2105124
Wang Q, Gong J, Huang X, Yu H, Xue F (2009) In vitro evaluation of the activity of microencapsulated carvacrol against Escherichia coli with K88 pili. J Appl Microbiol 107:1781–1788. https://doi.org/10.1111/j.1365-2672.2009.04374.x
Yadav N, Yadav R, Goyal A (2014) Chemistry of terpenoids. Int J Pharm Sci Rev Res 27:272–278
Yang G, Ge S, Singh R, Basu S, Shatzer K, Zen M, Liu J, Tu Y, Zhang C, Wei J, Shi J, Zhu L, Liu Z, Wang Y, Gao S, Hu M (2017) Glucuronidation: driving factors and their impact on glucuronide disposition. Drug Metab Rev 49:105–138. https://doi.org/10.1080/03602532.2017.1293682
Yang W, Chen X, Li Y, Guo S, Wang Z, Yu X (2020) Advances in pharmacological activities of terpenoids. Nat Prod Comm 15:1934578X2090355. https://doi.org/10.1177/1934578X20903555
Yildiz ZI, Celebioglu A, Kilic ME, Durgun E, Uyar T (2018) Fast-dissolving carvacrol/cyclodextrin inclusion complex electrospun fibers with enhanced thermal stability, water solubility, and antioxidant activity. J Mater Sci 53:15837–15849. https://doi.org/10.1007/s10853-018-2750-1
Yildiz S, Turan S, Kiralan M, Ramadan MF (2021) Antioxidant properties of thymol, carvacrol, and thymoquinone and its efficiencies on the stabilization of refined and stripped corn oils. Food Measure 15:621–632. https://doi.org/10.1007/s11694-020-00665-0
Yin QH, Yan FX, Zu XY, Wu YH, Wu XP, Liao MC, Deng SW, Yin LL, Zhuang YZ (2012) Anti-proliferative and pro-apoptotic effect of carvacrol on human hepatocellular carcinoma cell line HepG-2. Cytotechnology 64:43–51. https://doi.org/10.1007/s10616-011-9389-y
Zamanian MY, Kujawska M, Nikbakhtzadeh M, Hassanshahi A, Ramezanpour S, Kamiab Z, Bazmandegan G (2021) Carvacrol as a potential neuroprotective agent for neurological diseases: a systematic review article. CNS Neurol Disord Drug Targets 20:942–953. https://doi.org/10.2174/1871527320666210506185042
Zengin Kurt B, Durdagi S, Celebi G, Ekhteiari Salmas R, Sonmez F (2020) Synthesis, anticholinesterase activity and molecular modeling studies of novel carvacrol-substituted amide derivatives. J Biomol Struct Dyn 38:841–859. https://doi.org/10.1080/07391102.2019.1590243
Zeytun H, Özkorkmaz EG (2021) Effects of carvacrol in an experimentally induced esophageal burn model: expression of VEGF and caspase-3 proteins. J Invest Surg 34:408–416. https://doi.org/10.1080/08941939.2019.1637484
Zotti M, Colaianna M, Morgese MG, Tucci P, Schiavone S, Avato P, Trabace L (2013) Carvacrol: from ancient flavoring to neuromodulatory agent. Molecules 18:6161–6172. https://doi.org/10.3390/molecules18066161
Acknowledgements
Senior Research Associateship (SRA) [13(9234-A)/2023-POOL] from the Council of Scientific and Industrial Research (CSIR-Govt of India) under the Pool Scientist’s Scheme in favor of Sheikh Tahir Majeed and DST-INSPIRE fellowship (DST/INSPIRE Fellowship/2019/IF190487) and in favor of Suhail Ahmad Mir are duly acknowledged.
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TA, RM, RB, and IJ performed literature survey and drafted the manuscript content. TA wrote the manuscript. GNB and KIA supervised the manuscript writing. STM conceived the idea and edited the manuscript. All the authors reviewed the final submitted manuscript.
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Ali, T., Majeed, S.T., Majeed, R. et al. Recent Advances in the Pharmacological Properties and Molecular Mechanisms of Carvacrol. Rev. Bras. Farmacogn. 34, 35–47 (2024). https://doi.org/10.1007/s43450-023-00433-3
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DOI: https://doi.org/10.1007/s43450-023-00433-3