Carvacrol Protect Hippocampal Neurons Against Hydroxychloroquine-induced Damage: in vitro Study

Ayşegül Yılmaz; Ahmet Hacımüftüoğlu; Betül Çiçek; Mesut Isık; Adem Necip; Ali.tgzd Tgzd

Research Article

Year 2023, Volume: 1 Issue: 1, 16 - 26, 30.04.2023

Ayşegül Yılmaz Ahmet Hacımüftüoğlu Betül Çiçek Mesut Isık Adem Necip Ali.tgzd Tgzd

Abstract

References

1. Aazza, S., Lyoussi, B., & Miguel, M. G. (2011, Sep 7). Antioxidant and antiacetylcholinesterase activities of some commercial essential oils and their major compounds. Molecules, 16(9), 7672-7690. https://doi.org/10.3390/molecules16097672
2. Abdelli, I., Hassani, F., Bekkel Brikci, S., & Ghalem, S. (2021, Jun). In silico study the inhibition of angiotensin converting enzyme 2 receptor of COVID-19 by Ammoides verticillata components harvested from Western Algeria. J Biomol Struct Dyn, 39(9), 3263-3276. https://doi.org/10.1080/07391102.2020.1763199
3. Ali Taghizadehghalehjoughi, Ahmet Hacimuftuoglu, & Yilmaz, A. (2019). Na+ channel blocker enhances metformin effects on neuroblastoma cell line. Medicine Science, 8(3), 636-640.
4. Aysegul YILMAZ, Ali TAGHİZADEHGHALEHJOUGHİ, Ahmet HACİMUFTUOGLU, & TÜRKMEN, A. (2021). Investigation of Aloe Vera Barbadensis Miller Leaf Extract Effects On Glutamate and Glyphosate Induced Toxicity: In Vitro Study. Journal of Anatolian Environmental and Animal Sciences, 6(3), 376-381. https://doi.org/https://doi.org/10.35229/jaes.953830
5. Bianchini, A. E., Garlet, Q. I., da Cunha, J. A., Bandeira, G. J., Brusque, I. C. M., Salbego, J., Heinzmann, B. M., & Baldisserotto, B. (2017, Oct 19). Monoterpenoids (thymol, carvacrol and S-(+)-linalool) with anesthetic activity in silver catfish (Rhamdia quelen): evaluation of acetylcholinesterase and GABAergic activity. Braz J Med Biol Res, 50(12), e6346. https://doi.org/10.1590/1414-431X20176346
6. Bruinink, A., Zimmermann, G., & Riesen, F. (1991). Neurotoxic effects of chloroquine in vitro. Arch Toxicol, 65(6), 480-484. https://doi.org/10.1007/BF01977360
7. Cortegiani, A., Ingoglia, G., Ippolito, M., Giarratano, A., & Einav, S. (2020, Jun). A systematic review on the efficacy and safety of chloroquine for the treatment of COVID-19. J Crit Care, 57, 279-283. https://doi.org/10.1016/j.jcrc.2020.03.005
8. Fang, L., Neutzner, A., Turtschi, S., Flammer, J., & Mozaffarieh, M. (2015, May 22). Comet assay as an indirect measure of systemic oxidative stress. J Vis Exp(99), e52763. https://doi.org/10.3791/52763
9. Gandhi, G. R., Vasconcelos, A. B. S., Haran, G. H., Calisto, V., Jothi, G., Quintans, J. S. S., Cuevas, L. E., Narain, N., Junior, L. J. Q., Cipolotti, R., & Gurgel, R. Q. (2020, Jul 15). Essential oils and its bioactive compounds modulating cytokines: A systematic review on anti-asthmatic and immunomodulatory properties. Phytomedicine, 73, 152854. https://doi.org/10.1016/j.phymed.2019.152854
10. Giovanella, F., Ferreira, G. K., de Pra, S. D., Carvalho-Silva, M., Gomes, L. M., Scaini, G., Goncalves, R. C., Michels, M., Galant, L. S., Longaretti, L. M., Dajori, A. L., Andrade, V. M., Dal-Pizzol, F., Streck, E. L., & de Souza, R. P. (2015, Aug). Effects of primaquine and chloroquine on oxidative stress parameters in rats. An Acad Bras Cienc, 87(2 Suppl), 1487-1496. https://doi.org/10.1590/0001-3765201520140637
11. Guan, X., Li, X., Yang, X., Yan, J., Shi, P., Ba, L., Cao, Y., & Wang, P. (2019, Oct 15). The neuroprotective effects of carvacrol on ischemia/reperfusion-induced hippocampal neuronal impairment by ferroptosis mitigation. Life Sci, 235, 116795. https://doi.org/10.1016/j.lfs.2019.116795
12. Guimaraes, A. G., Oliveira, G. F., Melo, M. S., Cavalcanti, S. C., Antoniolli, A. R., Bonjardim, L. R., Silva, F. A., Santos, J. P., Rocha, R. F., Moreira, J. C., Araujo, A. A., Gelain, D. P., & Quintans-Junior, L. J. (2010, Dec). Bioassay-guided evaluation of antioxidant and antinociceptive activities of carvacrol. Basic Clin Pharmacol Toxicol, 107(6), 949-957. https://doi.org/10.1111/j.1742-7843.2010.00609.x
13. Hakimi, Z., Salmani, H., Marefati, N., Arab, Z., Gholamnezhad, Z., Beheshti, F., Shafei, M. N., & Hosseini, M. (2020, Apr). Protective Effects of Carvacrol on Brain Tissue Inflammation and Oxidative Stress as well as Learning and Memory in Lipopolysaccharide-Challenged Rats. Neurotox Res, 37(4), 965-976. https://doi.org/10.1007/s12640-019-00144-5
14. Hu, B., Guo, H., Zhou, P., & Shi, Z. L. (2021, Mar). Characteristics of SARS-CoV-2 and COVID-19. Nat Rev Microbiol, 19(3), 141-154. https://doi.org/10.1038/s41579-020-00459-7
15. Javed, H., Meeran, M. F. N., Jha, N. K., & Ojha, S. (2020). Carvacrol, a Plant Metabolite Targeting Viral Protease (M(pro)) and ACE2 in Host Cells Can Be a Possible Candidate for COVID-19. Front Plant Sci, 11, 601335. https://doi.org/10.3389/fpls.2020.601335
16. Kim, G. H., Kim, J. E., Rhie, S. J., & Yoon, S. (2015, Dec). The Role of Oxidative Stress in Neurodegenerative Diseases. Exp Neurobiol, 24(4), 325-340. https://doi.org/10.5607/en.2015.24.4.325
17. Klouda, C. B., & Stone, W. L. (2020, Sep 21). Oxidative Stress, Proton Fluxes, and Chloroquine/Hydroxychloroquine Treatment for COVID-19. Antioxidants (Basel), 9(9). https://doi.org/10.3390/antiox9090894
18. Kulkarni, S. A., Nagarajan, S. K., Ramesh, V., Palaniyandi, V., Selvam, S. P., & Madhavan, T. (2020, Dec 5). Computational evaluation of major components from plant essential oils as potent inhibitors of SARS-CoV-2 spike protein. J Mol Struct, 1221, 128823. https://doi.org/10.1016/j.molstruc.2020.128823
19. Kundi, H., Ates, I., Kiziltunc, E., Cetin, M., Cicekcioglu, H., Neselioglu, S., Erel, O., & Ornek, E. (2015, Nov). A novel oxidative stress marker in acute myocardial infarction; thiol/disulphide homeostasis. Am J Emerg Med, 33(11), 1567-1571. https://doi.org/10.1016/j.ajem.2015.06.016
20. Llana-Ruiz-Cabello, M., Gutierrez-Praena, D., Puerto, M., Pichardo, S., Jos, A., & Camean, A. M. (2015, Jun). In vitro pro-oxidant/antioxidant role of carvacrol, thymol and their mixture in the intestinal Caco-2 cell line. Toxicol In Vitro, 29(4), 647-656. https://doi.org/10.1016/j.tiv.2015.02.006
21. Lopez, M. D., Campoy, F. J., Pascual-Villalobos, M. J., Munoz-Delgado, E., & Vidal, C. J. (2015, Mar 5). Acetylcholinesterase activity of electric eel is increased or decreased by selected monoterpenoids and phenylpropanoids in a concentration-dependent manner. Chem Biol Interact, 229, 36-43. https://doi.org/10.1016/j.cbi.2015.01.006
22. Satarker, S., Ahuja, T., Banerjee, M., E, V. B., Dogra, S., Agarwal, T., & Nampoothiri, M. (2020, Aug 24). Hydroxychloroquine in COVID-19: Potential Mechanism of Action Against SARS-CoV-2. Curr Pharmacol Rep, 1-9. https://doi.org/10.1007/s40495-020-00231-8
23. Sieb, J. P., Milone, M., & Engel, A. G. (1996, Mar 18). Effects of the quinoline derivatives quinine, quinidine, and chloroquine on neuromuscular transmission. Brain Res, 712(2), 179-189. https://doi.org/10.1016/0006-8993(95)01349-0
24. Wang, P., Luo, Q., Qiao, H., Ding, H., Cao, Y., Yu, J., Liu, R., Zhang, Q., Zhu, H., & Qu, L. (2017). The Neuroprotective Effects of Carvacrol on Ethanol-Induced Hippocampal Neurons Impairment via the Antioxidative and Antiapoptotic Pathways. Oxid Med Cell Longev, 2017, 4079425. https://doi.org/10.1155/2017/4079425

Carvacrol Protect Hippocampal Neurons Against Hydroxychloroquine-induced Damage: in vitro Study

Year 2023, Volume: 1 Issue: 1, 16 - 26, 30.04.2023

Ayşegül Yılmaz Ahmet Hacımüftüoğlu Betül Çiçek Mesut Isık Adem Necip Ali.tgzd Tgzd

Abstract

The use of hydroxychloroquine, an antimalarial drug, in the treatment of Covid-19 disease, which has turned into a worldwide epidemic, was initially viewed positively. However, the lack of evidence for its use in treatment and even neuronal side effects caused hydroxychloroquine to be approached with suspicion. Carvacrol, on the other hand, is a very interesting ingredient with its anti-oxidant, anti-inflammatory, and anti-cancer properties. Primary neuron culture was prepared for our study. Carvacrol (10, 25, 50, and 100 mg/L), hydroxychloroquine (10,20,40, and 80µM), hydroxychloroquine+carvacrol groups (10µM+10mg/L, 20µM+25mg/L, 40µM+50mg/L, 80µM+100mg/L) were applied to neuron culture for 24 and 48 hours. After the application, results were obtained with MTT, TAS, TOS, Thiol analyses, and acetylcholinesterase (AChE), butyrylcholinesterase (BChE) activities. According to our MTT results, carvacrol (100mg/mL) increased neuronal viability by ~10% in the combined group compared to pure hydroxychloroquine (80µM). The same dose of carvacrol reduced the antioxidant level 1.3 times. Doses of carvacrol alone did not affect thiol levels but increased in combination with hydroxychloroquine(431µmol/L). It is now known that Covid-19 is associated with neurodegenerative diseases. Recent studies have shown that hydroxychloroquine, which is seen as a hope for the global epidemic, causes oxidative stress on neurons. In our study, we designed to both provide protection and prevent the occurrence of side effects by using carvacrol against the neurodegenerative effects of hydroxychloroquine.

Keywords

Carvacrol, covid-19, Neuroprotective, Neurons, Hydroxychloroquine

References

1. Aazza, S., Lyoussi, B., & Miguel, M. G. (2011, Sep 7). Antioxidant and antiacetylcholinesterase activities of some commercial essential oils and their major compounds. Molecules, 16(9), 7672-7690. https://doi.org/10.3390/molecules16097672
2. Abdelli, I., Hassani, F., Bekkel Brikci, S., & Ghalem, S. (2021, Jun). In silico study the inhibition of angiotensin converting enzyme 2 receptor of COVID-19 by Ammoides verticillata components harvested from Western Algeria. J Biomol Struct Dyn, 39(9), 3263-3276. https://doi.org/10.1080/07391102.2020.1763199
3. Ali Taghizadehghalehjoughi, Ahmet Hacimuftuoglu, & Yilmaz, A. (2019). Na+ channel blocker enhances metformin effects on neuroblastoma cell line. Medicine Science, 8(3), 636-640.
4. Aysegul YILMAZ, Ali TAGHİZADEHGHALEHJOUGHİ, Ahmet HACİMUFTUOGLU, & TÜRKMEN, A. (2021). Investigation of Aloe Vera Barbadensis Miller Leaf Extract Effects On Glutamate and Glyphosate Induced Toxicity: In Vitro Study. Journal of Anatolian Environmental and Animal Sciences, 6(3), 376-381. https://doi.org/https://doi.org/10.35229/jaes.953830
5. Bianchini, A. E., Garlet, Q. I., da Cunha, J. A., Bandeira, G. J., Brusque, I. C. M., Salbego, J., Heinzmann, B. M., & Baldisserotto, B. (2017, Oct 19). Monoterpenoids (thymol, carvacrol and S-(+)-linalool) with anesthetic activity in silver catfish (Rhamdia quelen): evaluation of acetylcholinesterase and GABAergic activity. Braz J Med Biol Res, 50(12), e6346. https://doi.org/10.1590/1414-431X20176346
6. Bruinink, A., Zimmermann, G., & Riesen, F. (1991). Neurotoxic effects of chloroquine in vitro. Arch Toxicol, 65(6), 480-484. https://doi.org/10.1007/BF01977360
7. Cortegiani, A., Ingoglia, G., Ippolito, M., Giarratano, A., & Einav, S. (2020, Jun). A systematic review on the efficacy and safety of chloroquine for the treatment of COVID-19. J Crit Care, 57, 279-283. https://doi.org/10.1016/j.jcrc.2020.03.005
8. Fang, L., Neutzner, A., Turtschi, S., Flammer, J., & Mozaffarieh, M. (2015, May 22). Comet assay as an indirect measure of systemic oxidative stress. J Vis Exp(99), e52763. https://doi.org/10.3791/52763
9. Gandhi, G. R., Vasconcelos, A. B. S., Haran, G. H., Calisto, V., Jothi, G., Quintans, J. S. S., Cuevas, L. E., Narain, N., Junior, L. J. Q., Cipolotti, R., & Gurgel, R. Q. (2020, Jul 15). Essential oils and its bioactive compounds modulating cytokines: A systematic review on anti-asthmatic and immunomodulatory properties. Phytomedicine, 73, 152854. https://doi.org/10.1016/j.phymed.2019.152854
10. Giovanella, F., Ferreira, G. K., de Pra, S. D., Carvalho-Silva, M., Gomes, L. M., Scaini, G., Goncalves, R. C., Michels, M., Galant, L. S., Longaretti, L. M., Dajori, A. L., Andrade, V. M., Dal-Pizzol, F., Streck, E. L., & de Souza, R. P. (2015, Aug). Effects of primaquine and chloroquine on oxidative stress parameters in rats. An Acad Bras Cienc, 87(2 Suppl), 1487-1496. https://doi.org/10.1590/0001-3765201520140637
11. Guan, X., Li, X., Yang, X., Yan, J., Shi, P., Ba, L., Cao, Y., & Wang, P. (2019, Oct 15). The neuroprotective effects of carvacrol on ischemia/reperfusion-induced hippocampal neuronal impairment by ferroptosis mitigation. Life Sci, 235, 116795. https://doi.org/10.1016/j.lfs.2019.116795
12. Guimaraes, A. G., Oliveira, G. F., Melo, M. S., Cavalcanti, S. C., Antoniolli, A. R., Bonjardim, L. R., Silva, F. A., Santos, J. P., Rocha, R. F., Moreira, J. C., Araujo, A. A., Gelain, D. P., & Quintans-Junior, L. J. (2010, Dec). Bioassay-guided evaluation of antioxidant and antinociceptive activities of carvacrol. Basic Clin Pharmacol Toxicol, 107(6), 949-957. https://doi.org/10.1111/j.1742-7843.2010.00609.x
13. Hakimi, Z., Salmani, H., Marefati, N., Arab, Z., Gholamnezhad, Z., Beheshti, F., Shafei, M. N., & Hosseini, M. (2020, Apr). Protective Effects of Carvacrol on Brain Tissue Inflammation and Oxidative Stress as well as Learning and Memory in Lipopolysaccharide-Challenged Rats. Neurotox Res, 37(4), 965-976. https://doi.org/10.1007/s12640-019-00144-5
14. Hu, B., Guo, H., Zhou, P., & Shi, Z. L. (2021, Mar). Characteristics of SARS-CoV-2 and COVID-19. Nat Rev Microbiol, 19(3), 141-154. https://doi.org/10.1038/s41579-020-00459-7
15. Javed, H., Meeran, M. F. N., Jha, N. K., & Ojha, S. (2020). Carvacrol, a Plant Metabolite Targeting Viral Protease (M(pro)) and ACE2 in Host Cells Can Be a Possible Candidate for COVID-19. Front Plant Sci, 11, 601335. https://doi.org/10.3389/fpls.2020.601335
16. Kim, G. H., Kim, J. E., Rhie, S. J., & Yoon, S. (2015, Dec). The Role of Oxidative Stress in Neurodegenerative Diseases. Exp Neurobiol, 24(4), 325-340. https://doi.org/10.5607/en.2015.24.4.325
17. Klouda, C. B., & Stone, W. L. (2020, Sep 21). Oxidative Stress, Proton Fluxes, and Chloroquine/Hydroxychloroquine Treatment for COVID-19. Antioxidants (Basel), 9(9). https://doi.org/10.3390/antiox9090894
18. Kulkarni, S. A., Nagarajan, S. K., Ramesh, V., Palaniyandi, V., Selvam, S. P., & Madhavan, T. (2020, Dec 5). Computational evaluation of major components from plant essential oils as potent inhibitors of SARS-CoV-2 spike protein. J Mol Struct, 1221, 128823. https://doi.org/10.1016/j.molstruc.2020.128823
19. Kundi, H., Ates, I., Kiziltunc, E., Cetin, M., Cicekcioglu, H., Neselioglu, S., Erel, O., & Ornek, E. (2015, Nov). A novel oxidative stress marker in acute myocardial infarction; thiol/disulphide homeostasis. Am J Emerg Med, 33(11), 1567-1571. https://doi.org/10.1016/j.ajem.2015.06.016
20. Llana-Ruiz-Cabello, M., Gutierrez-Praena, D., Puerto, M., Pichardo, S., Jos, A., & Camean, A. M. (2015, Jun). In vitro pro-oxidant/antioxidant role of carvacrol, thymol and their mixture in the intestinal Caco-2 cell line. Toxicol In Vitro, 29(4), 647-656. https://doi.org/10.1016/j.tiv.2015.02.006
21. Lopez, M. D., Campoy, F. J., Pascual-Villalobos, M. J., Munoz-Delgado, E., & Vidal, C. J. (2015, Mar 5). Acetylcholinesterase activity of electric eel is increased or decreased by selected monoterpenoids and phenylpropanoids in a concentration-dependent manner. Chem Biol Interact, 229, 36-43. https://doi.org/10.1016/j.cbi.2015.01.006
22. Satarker, S., Ahuja, T., Banerjee, M., E, V. B., Dogra, S., Agarwal, T., & Nampoothiri, M. (2020, Aug 24). Hydroxychloroquine in COVID-19: Potential Mechanism of Action Against SARS-CoV-2. Curr Pharmacol Rep, 1-9. https://doi.org/10.1007/s40495-020-00231-8
23. Sieb, J. P., Milone, M., & Engel, A. G. (1996, Mar 18). Effects of the quinoline derivatives quinine, quinidine, and chloroquine on neuromuscular transmission. Brain Res, 712(2), 179-189. https://doi.org/10.1016/0006-8993(95)01349-0
24. Wang, P., Luo, Q., Qiao, H., Ding, H., Cao, Y., Yu, J., Liu, R., Zhang, Q., Zhu, H., & Qu, L. (2017). The Neuroprotective Effects of Carvacrol on Ethanol-Induced Hippocampal Neurons Impairment via the Antioxidative and Antiapoptotic Pathways. Oxid Med Cell Longev, 2017, 4079425. https://doi.org/10.1155/2017/4079425

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Details

Primary Language	English
Subjects	Clinical Sciences
Journal Section	Research Articles
Authors	Ayşegül Yılmaz 0000-0001-5843-1661 Ahmet Hacımüftüoğlu 0000-0002-9658-3313 Betül Çiçek Mesut Isık Adem Necip Ali.tgzd Tgzd
Publication Date	April 30, 2023
Published in Issue	Year 2023 Volume: 1 Issue: 1

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APA	Yılmaz, A., Hacımüftüoğlu, A., Çiçek, B., Isık, M., et al. (2023). Carvacrol Protect Hippocampal Neurons Against Hydroxychloroquine-induced Damage: in vitro Study. Recent Trends in Pharmacology, 1(1), 16-26.

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