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image of Thymol and Carvacrol as Potential Tocolytic and Anti-inflammatory Agents in Pregnant Rat Uterus
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Abstract

Introduction:

This work aimed to evaluate the anti-inflammatory and myorelaxant effect of thymol (TM) and carvacrol (CAR) in the pregnant rat uterus. Both compounds exhibit considerable antimicrobial, antispasmodic, and anti-inflammatory effects and due to these properties, they were studied in this model of premature birth induced by infection.

Method:

All uterine tissues were studied in uterine contraction tests to determine the inhibitory effect of TM, CAR (10, 56, 100, 150, and 230 µM), and nifedipine (a calcium channel antagonist) on phasic and tonic contraction induced by electro- and pharmacomechanical stimuli. The quantitative determination of cyclic adenosine monophosphate (cAMP) induced by TM and CAR in the uterine lysate was carried out by ELISA. For the determination of the anti-inflammatory effect of TM, the pro-inflammatory cytokine, interleukin (IL)-1β, in uterine samples stimulated with lipopolysaccharide (LPS) was measured. Forskolin (FSK) was used as a positive control to evaluate the cAMP and cytokine levels. TM, CAR, and nifedipine inhibited the uterine contractions at the highest concentration level, however, nifedipine was the most equipotent (<0.05). In addition, TM and CAR did not increase the intracellular cAMP production in comparison with FSK (<0.05). However, both compounds were able to decrease the LPS-induced production in a concentration-dependent manner that was considered statistically significant (>0.05).

Results:

Finally, both the anti-inflammatory and uterine relaxing effects induced by TM and CAR were neither associated with the increase in cAMP levels nor with the production of IL-1β in pregnant rat uterine samples. Therefore, TM and CAR can be considered as alternative adjuvants for the treatment of infection-induced preterm labor. Before the experiments, an in-silico analysis was conducted using the Expaisy online server to evaluate the biological effects of thymol on uterine contraction.

Conclusion:

It is crucial to know the interaction and identification of genes encoding the Voltage-dependent L-type calcium channel subunit alpha-1C proteins, because of the functional relationship it may have in the inhibition of the uterine contraction. These properties place TM as a potentially safe and effective adjuvant agent in cases of preterm birth, an area of pharmacological treatment that requires urgent improvement.

© 2025 The Author(s). Published by Bentham Science Publisher.
This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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2025-01-09
2025-01-22

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References

  1. Ohuma E.O. Moller A.B. Bradley E. Chakwera S. Hussain-Alkhateeb L. Lewin A. Okwaraji Y.B. Mahanani W.R. Johansson E.W. Lavin T. Fernandez D.E. Domínguez G.G. de Costa A. Cresswell J.A. Krasevec J. Lawn J.E. Blencowe H. Requejo J. Moran A.C. National, regional, and global estimates of preterm birth in 2020, with trends from 2010: A systematic analysis. Lancet 2023 402 10409 1261 1271 10.1016/S0140‑6736(23)00878‑4 37805217
    [Google Scholar]
  2. Reddy M. McGannon C. Mol B.W. Looking back on preterm birth – The successes and failures. Acta Obstet. Gynecol. Scand. 2024 103 3 410 412 10.1111/aogs.14730 38356249
    [Google Scholar]
  3. Ramokolo V. Amabebe E. Cohen M.C. Anumba D.O.C. Editorial: Dialogues on preterm birth—causes and consequences, prevention and mitigation. Front. Glob. Women’s Health. 2023 4 1245570 10.3389/fgwh.2023.1245570 37711967
    [Google Scholar]
  4. Arman B.M. Binder N.K. de Alwis N. Beard S. Debruin D.A. Hayes A. Tong S. Kaitu’u-Lino T.J. Hannan N.J. Assessment of the tocolytic nifedipine in preclinical primary models of preterm birth. Sci. Rep. 2023 13 1 5646 10.1038/s41598‑023‑31077‑x 37024530
    [Google Scholar]
  5. Muñoz-Pérez V.M. Ortiz M.I. Ponce-Monter H.A. Monter-Pérez V. Barragán-Ramírez G. Anti-inflammatory and utero-relaxant effect of α-bisabolol on the pregnant human uterus. Korean J. Physiol. Pharmacol. 2018 22 4 391 398 10.4196/kjpp.2018.22.4.391 29962853
    [Google Scholar]
  6. Wilson A. Hodgetts-Morton V.A. Marson E.J. Markland A.D. Larkai E. Papadopoulou A. Coomarasamy A. Tobias A. Chou D. Oladapo O.T. Price M.J. Morris K. Gallos I.D. Tocolytics for delaying preterm birth: A network meta-analysis (0924). Cochrane Database Syst. Rev. 2022 8 8 CD014978 35947046
    [Google Scholar]
  7. Gómez-Chávez F. Correa D. Navarrete-Meneses P. Cancino-Diaz J.C. Cancino-Diaz M.E. Rodríguez-Martínez S. NF-κB and its regulators during pregnancy. Front. Immunol. 2021 12 679106 10.3389/fimmu.2021.679106 34025678
    [Google Scholar]
  8. Sykes L. MacIntyre D.A. Teoh T.G. Bennett P.R. Anti-inflammatory prostaglandins for the prevention of preterm labour. Reproduction 2014 148 2 R29 R40 10.1530/REP‑13‑0587 24890751
    [Google Scholar]
  9. Li J.K.H. Lai P.F. Tribe R.M. Johnson M.R. Transcription factors regulated by cAMP in smooth muscle of the myometrium at human parturition. Biochem. Soc. Trans. 2021 49 2 997 1011 10.1042/BST20201173 33860781
    [Google Scholar]
  10. Varley A. Koschinski A. Johnson M.R. Zaccolo M. cAMP compartmentalisation in human myometrial cells. Cells 2023 12 5 718 10.3390/cells12050718 36899855
    [Google Scholar]
  11. Zaccolo M. Zerio A. Lobo M.J. Subcellular organization of the cAMP signaling pathway. Pharmacol. Rev. 2021 73 1 278 309 10.1124/pharmrev.120.000086 33334857
    [Google Scholar]
  12. Sokol M.B. Sokhraneva V.A. Groza N.V. Mollaeva M.R. Yabbarov N.G. Chirkina M.V. Trufanova A.A. Popenko V.I. Nikolskaya E.D. Thymol-modified oleic and linoleic acids encapsulated in polymeric nanoparticles: Enhanced bioactivity, stability, and biomedical potential. Polymers 2023 16 1 72 10.3390/polym16010072 38201737
    [Google Scholar]
  13. Rathod N.B. Kulawik P. Ozogul F. Regenstein J.M. Ozogul Y. Biological activity of plant-based carvacrol and thymol and their impact on human health and food quality. Trends Food Sci. Technol. 2021 116 733 748 10.1016/j.tifs.2021.08.023
    [Google Scholar]
  14. Nagoor Meeran M.F. Javed H. Al Taee H. Azimullah S. Ojha S.K. Pharmacological properties and molecular mechanisms of thymol: Prospects for its therapeutic potential and pharmaceutical development. Front. Pharmacol. 2017 8 380 10.3389/fphar.2017.00380 28694777
    [Google Scholar]
  15. Abo Ghanima M.M. Alagawany M. Abd El-Hack M.E. Taha A. Elnesr S.S. Ajarem J. Allam A.A. Mahmoud A.M. Consequences of various housing systems and dietary supplementation of thymol, carvacrol, and euganol on performance, egg quality, blood chemistry, and antioxidant parameters. Poult. Sci. 2020 99 9 4384 4397 10.1016/j.psj.2020.05.028 32867982
    [Google Scholar]
  16. Galli G.M. Gerbet R.R. Griss L.G. Fortuoso B.F. Petrolli T.G. Boiago M.M. Souza C.F. Baldissera M.D. Mesadri J. Wagner R. da Rosa G. Mendes R.E. Gris A. Da Silva A.S. Combination of herbal components (curcumin, carvacrol, thymol, cinnamaldehyde) in broiler chicken feed: Impacts on response parameters, performance, fatty acid profiles, meat quality and control of coccidia and bacteria. Microb. Pathog. 2020 139 103916 10.1016/j.micpath.2019.103916 31812772
    [Google Scholar]
  17. Premrov Bajuk B. Prem L. Vake T. Žnidaršič N. Snoj T. The effect of thymol on acetylcholine-induced contractions of the rat ileum and uterus under ex vivo conditions. Front. Pharmacol. 2022 13 990654 10.3389/fphar.2022.990654 36339611
    [Google Scholar]
  18. Muñoz-Pérez V.M. Ortiz M.I. Gerardo-Muñoz L.S. Cariño-Cortés R. Salas-Casas A. Tocolytic effect of the monoterpenic phenol isomer, carvacrol, on the pregnant rat uterus. Chin. J. Physiol. 2020 63 5 204 210 10.4103/CJP.CJP_56_20 33109786
    [Google Scholar]
  19. Muñoz-Pérez V.M. Fernández-Martínez E. Ponce-Monter H. Ortiz M.I. Relaxant and anti-inflammatory effect of two thalidomide analogs as PDE-4 inhibitors in pregnant rat uterus. Korean J. Physiol. Pharmacol. 2017 21 4 429 437 10.4196/kjpp.2017.21.4.429 28706457
    [Google Scholar]
  20. Sehringer B. Schäfer W.R. Wetzka B. Deppert W.R. Brunner-Spahr R. Benedek E. Zahradnik H.P. Formation of proinflammatory cytokines in human term myometrium is stimulated by lipopolysaccharide but not by corticotropin-releasing hormone. J. Clin. Endocrinol. Metab. 2000 85 12 4859 4865 10.1210/jc.85.12.4859 11134154
    [Google Scholar]
  21. Frenette A.P. Rodríguez-Ramos T. Zanuzzo F. Ramsay D. Semple S.L. Soullière C. Rodríguez-Cornejo T. Heath G. McKenzie E. Iwanczyk J. Bruder M. Aucoin M.G. Gamperl A.K. Dixon B. Expression of Interleukin-1β protein in vitro, ex vivo and in vivo salmonid models. Dev. Comp. Immunol. 2023 147 104767 10.1016/j.dci.2023.104767 37406840
    [Google Scholar]
  22. Fuentes C. Fuentes A. Barat J.M. Ruiz M.J. Relevant essential oil components: A minireview on increasing applications and potential toxicity. Toxicol. Mech. Methods 2021 31 8 559 565 10.1080/15376516.2021.1940408 34112059
    [Google Scholar]
  23. Li H. Ji B. Xu T. Zhao M. Zhang Y. Sun M. Xu Z. Gao Q. Antenatal hypoxia affects pulmonary artery contractile functions via downregulating L‐type Ca 2+ Channels subunit Alpha1 C in adult male offspring. J. Am. Heart Assoc. 2021 10 8 e019922 10.1161/JAHA.120.019922 33843249
    [Google Scholar]
  24. Khandre V. Potdar J. Keerti A. Preterm birth: An overview. Cureus 2022 14 12 e33006 36712773
    [Google Scholar]
  25. Goldenberg R.L. Culhane J.F. Iams J.D. Romero R. Epidemiology and causes of preterm birth. Lancet 2008 371 9606 75 84 10.1016/S0140‑6736(08)60074‑4 18177778
    [Google Scholar]
  26. Simmons L.E. Rubens C.E. Darmstadt G.L. Gravett M.G. Preventing preterm birth and neonatal mortality: Exploring the epidemiology, causes, and interventions. Semin. Perinatol. 2010 34 6 408 415 10.1053/j.semperi.2010.09.005 21094415
    [Google Scholar]
  27. Njamen D. Mvondo M. Djiogue S. Ketcha Wanda G. Magne Nde C. Vollmer G. Phytotherapy and women’s reproductive health: The Cameroonian perspective. Planta Med. 2013 79 7 600 611 10.1055/s‑0032‑1328326 23539352
    [Google Scholar]
  28. Karati D. Varghese R. Mahadik K.R. Sharma R. Kumar D. Plant bioactives in the treatment of inflammation of skeletal muscles: A molecular perspective. Evid. Based Complement. Alternat. Med. 2022 2022 1 18 10.1155/2022/4295802 35911155
    [Google Scholar]
  29. Mbemya G.T. Vieira L.A. Canafistula F.G. Pessoa O.D.L. Rodrigues A.P.R. Reports on in vivo and in vitro contribution of medicinal plants to improve the female reproductive function. Reproduction & Climacteric 2017 32 2 109 119 10.1016/j.recli.2016.11.002
    [Google Scholar]
  30. Salehi B. Mishra A.P. Shukla I. Sharifi-Rad M. Contreras M.M. Segura-Carretero A. Fathi H. Nasrabadi N.N. Kobarfard F. Sharifi-Rad J. Thymol, thyme, and other plant sources: Health and potential uses. Phytother. Res. 2018 32 9 1688 1706 10.1002/ptr.6109 29785774
    [Google Scholar]
  31. Garrett A.S. Means S.A. Roesler M.W. Miller K.J.W. Cheng L.K. Clark A.R. Modeling and experimental approaches for elucidating multi-scale uterine smooth muscle electro- and mechano-physiology: A review. Front. Physiol. 2022 13 1017649 10.3389/fphys.2022.1017649 36277190
    [Google Scholar]
  32. Rehman N.U. Ansari M.N. Haile T. Karim A. Abujheisha K.Y. Ahamad S.R. Imam F. Possible tracheal relaxant and antimicrobial effects of the essential oil of ethiopian thyme species (Thymus serrulatus Hochst. ex Benth.): A multiple mechanistic approach. Front. Pharmacol. 2021 12 615228 10.3389/fphar.2021.615228 33883992
    [Google Scholar]
  33. Patra C. Disclosure: Kristoff Foster declares no relevant financial relationships with ineligible companies. Disclosure: James Corley declares no relevant financial relationships with ineligible companies. Disclosure: Manjari Dimri declares no relevant financial relationships with ineligible companies. Disclosure: Mark Brady declares no relevant financial relationships with ineligible companies.. Biochemistry StatPearls Treasure Island (FL) 2024
    [Google Scholar]
  34. Yan K. Gao L.N. Cui Y.L. Zhang Y. Zhou X. The cyclic AMP signaling pathway: Exploring targets for successful drug discovery (Review). Mol. Med. Rep. 2016 13 5 3715 3723 10.3892/mmr.2016.5005 27035868
    [Google Scholar]
  35. Gárriz A. Morokuma J. Toribio D. Zoukhri D. Role of the adenylate cyclase/cyclic AMP pathway in oxytocin-induced lacrimal gland myoepithelial cells contraction. Exp. Eye Res. 2023 233 109526 10.1016/j.exer.2023.109526 37290630
    [Google Scholar]
  36. Fricke E.M. Elgin T.G. Gong H. Reese J. Gibson-Corley K.N. Weiss R.M. Zimmerman K. Bowdler N.C. Kalantera K.M. Mills D.A. Underwood M.A. McElroy S.J. Lipopolysaccharide‐induced maternal inflammation induces direct placental injury without alteration in placental blood flow and induces a secondary fetal intestinal injury that persists into adulthood. Am. J. Reprod. Immunol. 2018 79 5 e12816 10.1111/aji.12816 29369434
    [Google Scholar]
  37. Boyle A.K. Rinaldi S.F. Norman J.E. Stock S.J. Preterm birth: Inflammation, fetal injury and treatment strategies. J. Reprod. Immunol. 2017 119 62 66 10.1016/j.jri.2016.11.008 28122664
    [Google Scholar]
  38. Owen J.C. Garrick S.P. Peterson B.M. Berger P.J. Nold M.F. Sehgal A. Nold-Petry C.A. The role of interleukin-1 in perinatal inflammation and its impact on transitional circulation. Front Pediatr. 2023 11 1130013 10.3389/fped.2023.1130013 36994431
    [Google Scholar]
  39. Park S. Shin J. Bae J. Han D. Park S.R. Shin J. Lee S.K. Park H.W. SIRT1 alleviates LPS-Induced IL-1β production by suppressing NLRP3 inflammasome activation and ROS production in trophoblasts. Cells 2020 9 3 728 10.3390/cells9030728 32188057
    [Google Scholar]
  40. Lopez T.E. Zhang H. Bouysse E. Neiers F. Ye X.Y. Garrido C. Wendremaire M. Lirussi F. A pivotal role for the IL-1β and the inflammasome in preterm labor. Sci. Rep. 2024 14 1 4234 10.1038/s41598‑024‑54507‑w 38378749
    [Google Scholar]
  41. Das G. Patra J.K. Kang S.S. Shin H.S. Pharmaceutical importance of some promising plant species with special reference to the isolation and extraction of bioactive compounds: A review. Curr. Pharm. Biotechnol. 2022 23 1 15 29 10.2174/1389201022666210122125854 33480340
    [Google Scholar]
  42. Yahia Y. Benabderrahim M.A. Tlili N. Bagues M. Nagaz K. Bioactive compounds, antioxidant and antimicrobial activities of extracts from different plant parts of two Ziziphus Mill. species. PLoS One 2020 15 5 e0232599 10.1371/journal.pone.0232599 32428000
    [Google Scholar]
  43. Gholijani N. Gharagozloo M. Farjadian S. Amirghofran Z. Modulatory effects of thymol and carvacrol on inflammatory transcription factors in lipopolysaccharide-treated macrophages. J. Immunotoxicol. 2016 13 2 157 164 10.3109/1547691X.2015.1029145 25812626
    [Google Scholar]
  44. Mars M. Néant I. Leclerc C. Bosch S. Rouviere C. Moreau M. Lachambre S. Paul C. Tauber M. Gravier E. Douzal C. Duplan H. Babin M. Brocario A. Thouvenin M.D. Guéry J.C. Redoules D. Lestienne F. Pelletier L. Savignac M. Cav1.4 calcium channels control cytokine production by human peripheral TH17 cells and psoriatic skin-infiltrating T cells. J. Allergy Clin. Immunol. 2022 149 4 1348 1357 10.1016/j.jaci.2021.09.030 34653514
    [Google Scholar]
  45. Veytia-Bucheli J.I. Alvarado-Velázquez D.A. Possani L.D. González-Amaro R. Rosenstein Y. The Ca2+ channel blocker verapamil inhibits the in vitro activation and function of T lymphocytes: A 2022 reappraisal. Pharmaceutics 2022 14 7 1478 10.3390/pharmaceutics14071478 35890372
    [Google Scholar]
  46. Das R. Burke T. Van Wagoner D.R. Plow E.F. L-type calcium channel blockers exert an antiinflammatory effect by suppressing expression of plasminogen receptors on macrophages. Circ. Res. 2009 105 2 167 175 10.1161/CIRCRESAHA.109.200311 19520970
    [Google Scholar]
  47. Bader A. Martini F. Schinella G.R. Rios J.L. Prieto J.M. Modulation of Cox-1, 5-, 12- and 15-Lox by popular herbal remedies used in southern Italy against psoriasis and other skin diseases. Phytother. Res. 2015 29 1 108 113 10.1002/ptr.5234 25278440
    [Google Scholar]
  48. Merecz-Sadowska A. Sitarek P. Śliwiński T. Zajdel R. Anti-inflammatory activity of extracts and pure compounds derived from plants via modulation of signaling pathways, especially PI3K/AKT in macrophages. Int. J. Mol. Sci. 2020 21 24 9605 10.3390/ijms21249605 33339446
    [Google Scholar]
  49. Zurfluh L. Duvaud L. Inci N. Potterat O. Simões-Wüst A.P. Mosbacher J. Bryophyllum pinnatum inhibits oxytocin and vasopressin signaling in myometrial cells. Planta Med. 2024 90 10 757 765 10.1055/a‑2303‑9608 38599625
    [Google Scholar]
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Thymol and Carvacrol as Potential Tocolytic and Anti-inflammatory Agents in Pregnant Rat Uterus
Bentham Science Publishers , e18761429342128; https://doi.org/10.2174/0118761429342128241231163610
/content/journals/cmp/10.2174/0118761429342128241231163610
/content/journals/cmp/10.2174/0118761429342128241231163610
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  • Article Type:     Research Article
Keywords: Cytokine ; Inflammation ; Carvacrol ; Infection ; Preterm birth ; Thymol

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