Saif M. Dmour, Haitham Qaralleh, Muhamad Al-Limoun, Khaled M. Khleifat, Moath Alqaraleh, Ali Abdallah Alqudah, Rakan M. Altarawneh
Saif M. Dmour1*, Haitham Qaralleh2, Muhamad Al-Limoun3, Khaled M. Khleifat4, Moath Alqaraleh5, Ali Abdallah Alqudah6, Rakan M. Altarawneh7
1Department of Laboratory Medical Sciences, Princess Aisha Bent Al-Hussein Faculty of Nursing and Health Sciences, Al Hussein bin Talal University, Jordan.
2Department of Medical Laboratory Sciences, Mutah University, Mutah, Karak, Jordan.
3Biology Department, Mutah University, Mutah, Karak, Jordan.
4Faculty of Allied Medical Sciences, Al-Ahliyya Amman University, Amman, Jordan.
5Pharmacological and Diagnostic Research Center (PDRC), Faculty of Pharmacy, Al-Ahliyya Amman University, Amman 19328, Jordan.
6Department of Applied Biology, Tafila Technical University, PO Box 179, 66110 Tafila, Jordan.
7Department of Chemistry, Faculty of Science, Mu'tah University, Al-Karak, Jordan.
Volume - 15,
Issue - 9,
Year - 2022
Resistance to antibiotics is a significant public health issue in preventing infectious diseases. This study was designed to evaluate the antibacterial activity of eucalyptol, ?-terpinene, p-cymol and punicalagin against Methicillin (Oxacillin) resistant strains. The synergistic effect of these compounds with cefotaxime against Staphylococcus aureus was investigated. The lowest MIC value observed was 0.08mg/mL for punicalagin against S. aureus, followed by the MIC values of punicalagin against E. aerogenes, E. coli and K. pneumoniae (0.16 - 0.63mg/mL). The activity of p-cymol against S. aureus is ranked second, as indicated by the MIC value (0.63mg/mL). The results of the combination study showed that the maximum Increase in Folding Area (IFA) was reported when punicalagin was combined with cefoxitin, cefotaxime, oxacillin, and piperacillin. An effective IFA was observed when p-cymol was tested with piperacillin, cefixime, cefotaxime, oxacillin, and cefoxitin. Based on the checkerboard assay, the MIC of cefotaxime decreased from 60 to 7.5µg/mL when combined with punicalagin indicating a significant synergistic effect between cefotaxime and punicalagin against S. aureus. In conclusion, punicalagin improved S. aureus susceptibility to cefotaxime, suggesting that using these two medicines together can reverse beta-lactam resistance in methicillin (oxacillin) resistant S. aureus. Further works are required to generalize this result and then it may be useful for treating diseases caused by methicillin (oxacillin) resistant strains.
Cite this article:
Saif M. Dmour, Haitham Qaralleh, Muhamad Al-Limoun, Khaled M. Khleifat, Moath Alqaraleh, Ali Abdallah Alqudah, Rakan M. Altarawneh. Combined Antibacterial activity of Eucalyptol, γ-terpinene, p-cymol and punicalagin with Cefotaxime against Methicillin (Oxacillin) Resistant Staphylococcus aureus Isolate. Research Journal of Pharmacy and Technology. 2022; 15(9):3905-1. doi: 10.52711/0974-360X.2022.00654
Saif M. Dmour, Haitham Qaralleh, Muhamad Al-Limoun, Khaled M. Khleifat, Moath Alqaraleh, Ali Abdallah Alqudah, Rakan M. Altarawneh. Combined Antibacterial activity of Eucalyptol, γ-terpinene, p-cymol and punicalagin with Cefotaxime against Methicillin (Oxacillin) Resistant Staphylococcus aureus Isolate. Research Journal of Pharmacy and Technology. 2022; 15(9):3905-1. doi: 10.52711/0974-360X.2022.00654 Available on: https://rjptonline.org/AbstractView.aspx?PID=2022-15-9-14
1. Chang Y, Chusri S, Sangthong R, McNeil E, Hu J, Du W, Li D, Fan X, Zhou H, and Chongsuvivatwong V. Clinical pattern of antibiotic overuse and misuse in primary healthcare hospitals in the southwest of China. PloS One 2019; 14: e0214779. https://doi.org/10.1371/journal.pone.0214779.
2. Sahib A, Abbas S, Hasson K, and Mahmoud M. Experience of Antibiotic Use and Resistance Among Pharmacy Students in the University of Kerbala. Journal of Basic and Applied Research in Biomedicine 2019; 5: 21-30.
3. Threats B. 2020. Data, 2019 AR Threats Report; 2019.
4. Kadri SS. Key takeaways from the US CDC’s 2019 antibiotic resistance threats report for frontline providers. Critical Care Medicine 2020. doi: 10.1097/CCM.0000000000004371.
5. González-Bello C. Antibiotic adjuvants–A strategy to unlock bacterial resistance to antibiotics. Bioorg Med Chem Lett 2017; 27: 4221-4228. https://doi.org/10.1016/j.bmcl.2017.08.027.
6. Todd PA, and Benfield P. Amoxicillin/clavulanic acid. Drugs 1990; 39: 264-307. https://doi.org/10.2165/00003495-199039020-00008.
7. Worthington RJ, and Melander C. Combination approaches to combat multidrug-resistant bacteria. Trends Biotechnol 2013; 31: 177-184. https://doi.org/10.1016/j.tibtech.2012.12.006.
8. Wright GD. Antibiotic adjuvants: rescuing antibiotics from resistance. Trends Microbiol 2016; 24: 862-871. https://doi.org/10.1016/j.tim.2016.06.009.
9. Jain C, Khatana S, and Vijayvergia R. Bioactivity of secondary metabolites of various plants: a review. International Journal of Pharmaceutical Sciences and Research 2019; 10: 494-498. 10.13040/IJPSR.0975-8232.10(2).494-04.
10. Jaafreh M, Khleifat K, Qaralleh H, and Al-limoun M. Antibacterial and Antioxidant Activities of Centeurea damascena Methanolic Extract. arXiv preprint arXiv:191102243 2019. https://doi.org/10.48550/arXiv.1911.02243.
11. Juergens LJ, Racké K, Tuleta I, Stoeber M, and Juergens UR. Anti-inflammatory effects of 1, 8-cineole (eucalyptol) improve glucocorticoid effects in vitro: a novel approach of steroid-sparing add-on therapy for COPD and asthma? Synergy 2017; 5: 1-8. https://doi.org/10.1016/j.synres.2017.08.001.
12. Jiang Z, Guo X, Zhang K, Sekaran G, Cao B, Zhao Q, Zhang S, Kirby GM, and Zhang X. The essential oils and eucalyptol from Artemisia vulgaris L. prevent acetaminophen-induced liver injury by activating Nrf2–Keap1 and enhancing APAP clearance through non-toxic metabolic pathway. Front Pharmacol 2019; 10: 782. https://doi.org/10.3389/fphar.2019.00782.
13. Guo Y, Baschieri A, Amorati R, and Valgimigli L. Synergic antioxidant activity of γ-terpinene with phenols and polyphenols enabled by hydroperoxyl radicals. Food Chem 2021; 345: 128468. https://doi.org/10.1016/j.foodchem.2020.128468.
14. Rivera-Yañez CR, Terrazas LI, Jimenez-Estrada M, Campos JE, Flores-Ortiz CM, Hernandez LB, Cruz-Sanchez T, Garrido-Fariña GI, Rodriguez-Monroy MA, and Canales-Martinez MM. Anti-Candida activity of Bursera morelensis Ramirez essential oil and two compounds, α-pinene and γ-terpinene—an in vitro study. Molecules 2017; 22: 2095. https://doi.org/10.3390/molecules22122095.
15. Balahbib A, El Omari N, Hachlafi NE, Lakhdar F, El Menyiy N, Salhi N, Mrabti HN, Bakrim S, Zengin G, and Bouyahya A. Health beneficial and pharmacological properties of p-cymene. Food Chem Toxicol 2021: 112259. https://doi.org/10.1016/j.fct.2021.112259.
16. El-Missiry MA, ElKomy MA, Othman AI, and AbouEl-Ezz AM. Punicalagin ameliorates the elevation of plasma homocysteine, amyloid-β, TNF-α and apoptosis by advocating antioxidants and modulating apoptotic mediator proteins in brain. Biomed Pharmacother 2018; 102: 472-480. https://doi.org/10.1016/j.biopha.2018.03.096.
17. Aladaileh SH, Al-Swailmi FK, Abukhalil MH, Ahmeda AF, and Mahmoud AM. Punicalagin prevents cisplatin-induced nephrotoxicity by attenuating oxidative stress, inflammatory response, and apoptosis in rats. Life Sci 2021: 120071. https://doi.org/10.1016/j.lfs.2021.120071.
18. Qaralleh H. Thymol rich thymbra capitata essential oil inhibits quorum sensing, virulence and biofilm formation of beta lactamase producing Pseudomonas aeruginosa. Natural Product Sciences 2019; 25: 172-180. https://doi.org/10.20307/nps.2019.25.2.172.
19. Lin L-T, Chen T-Y, Lin S-C, Chung C-Y, Lin T-C, Wang G-H, Anderson R, Lin C-C, and Richardson CD. Broad-spectrum antiviral activity of chebulagic acid and punicalagin against viruses that use glycosaminoglycans for entry. BMC Microbiol 2013; 13: 1-15. https://doi.org/10.1186/1471-2180-13-187.
20. Miladi H, Zmantar T, Kouidhi B, Al Qurashi YMA, Bakhrouf A, Chaabouni Y, Mahdouani K, and Chaieb K. Synergistic effect of eugenol, carvacrol, thymol, p-cymene and γ-terpinene on inhibition of drug resistance and biofilm formation of oral bacteria. Microb Pathog 2017; 112: 156-163. https://doi.org/10.1016/j.micpath.2017.09.057.
21. Eftekhar F, Raei F, Yousefzadi M, Ebrahimi SN, and Hadian J. Antibacterial activity and essential oil composition of Satureja spicigera from Iran. Zeitschrift für Naturforschung C 2009; 64: 20-24. https://doi.org/10.1515/znc-2009-1-204.
22. Merghni A, Noumi E, Hadded O, Dridi N, Panwar H, Ceylan O, Mastouri M, and Snoussi M. Assessment of the antibiofilm and antiquorum sensing activities of Eucalyptus globulus essential oil and its main component 1, 8-cineole against methicillin-resistant Staphylococcus aureus strains. Microb Pathog 2018; 118: 74-80. https://doi.org/10.1016/j.micpath.2018.03.006.
23. Gosset-Erard C, Zhao M, Lordel-Madeleine S, and Ennahar S. Identification of punicalagin as the bioactive compound behind the antimicrobial activity of pomegranate (Punica granatum L.) peels. Food Chem 2021; 352: 129396. https://doi.org/10.1016/j.foodchem.2021.129396.
24. Mun S-H, Kang O-H, Kong R, Zhou T, Kim S-A, Shin D-W, and Kwon D-Y. Punicalagin suppresses methicillin resistance of Staphylococcus aureus to oxacillin. J Pharmacol Sci 2018; 137: 317-323. https://doi.org/10.1016/j.jphs.2017.10.008.
25. Benameur Q, Gervasi T, Pellizzeri V, Pľuchtová M, Tali-Maama H, Assaous F, Guettou B, Rahal K, Gruľová D, and Dugo G. Antibacterial activity of Thymus vulgaris essential oil alone and in combination with cefotaxime against bla ESBL producing multidrug resistant Enterobacteriaceae isolates. Natural product research 2019; 33: 2647-2654. https://doi.org/10.1080/14786419.2018.1466124.
26. Clinical, and Institute LS. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically. Approved standard–ninth edition, M7-A9. 2012.
27. Clinical, and Institute LS. 2020. Performance Standards for Antimicrobial Susceptibility Testing. Approved Standard. CLSI Document M100. CLSI Wayne, PA.
28. Wambaugh MA, and Brown JC. High-throughput identification of synergistic drug combinations by the Overlap2 method. Journal of visualized experiments: JoVE 2018. DOI: 10.3791/57241.
29. Pence MA, Haste NM, Meharena HS, Olson J, Gallo RL, Nizet V, and Kristian SA. Beta-lactamase repressor BlaI modulates Staphylococcus aureus cathelicidin antimicrobial peptide resistance and virulence. PloS one 2015; 10: e0136605. https://doi.org/10.1371/journal.pone.0136605.g001
30. Carson C, and Riley T. Antimicrobial activity of the major components of the essential oil of Melaleuca alternifolia. Journal of applied bacteriology 1995; 78: 264-269. https://doi.org/10.1111/j.1365-2672.1995.tb05025.x.
31. Bagamboula C, Uyttendaele M, and Debevere J. Inhibitory effect of thyme and basil essential oils, carvacrol, thymol, estragol, linalool and p-cymene towards Shigella sonnei and S. flexneri. Food microbiology 2004; 21: 33-42. https://doi.org/10.1016/S0740-0020(03)00046-7
32. Rattanachaikunsopon P, and Phumkhachorn P. Assessment of factors influencing antimicrobial activity of carvacrol and cymene against Vibrio cholerae in food. Journal of bioscience and bioengineering 2010; 110: 614-619. https://doi.org/10.1016/j.jbiosc.2010.06.010
33. Li L, Li Z-W, Yin Z-Q, Wei Q, Jia R-Y, Zhou L-J, Xu J, Song X, Zhou Y, and Du Y-H. Antibacterial activity of leaf essential oil and its constituents from Cinnamomum longepaniculatum. International journal of clinical and experimental medicine 2014; 7: 1721. PMID: 25126170; PMCID: PMC4132134.
34. Lima TS, Silva MFS, Nunes XP, Colombo AV, Oliveira HP, Goto PL, Blanzat M, Piva HL, Tedesco AC, and Siqueira-Moura MP. Cineole-containing nanoemulsion: Development, stability, and antibacterial activity. Chemistry and Physics of Lipids 2021; 239: 105113. https://doi.org/10.1016/j.chemphyslip.2021.105113
35. Hendry E, Worthington T, Conway BR, and Lambert P. Antimicrobial efficacy of eucalyptus oil and 1, 8-cineole alone and in combination with chlorhexidine digluconate against microorganisms grown in planktonic and biofilm cultures. Journal of antimicrobial chemotherapy 2009; 64: 1219-1225. https://doi.org/10.1093/jac/dkp362.
36. Xu Y, Shi C, Wu Q, Zheng Z, Liu P, Li G, Peng X, and Xia X. Antimicrobial activity of punicalagin against Staphylococcus aureus and its effect on biofilm formation. Foodborne pathogens and disease 2017; 14: 282-287. https://doi.org/10.1089/fpd.2016.2226
37. Delgado B, Fernández PS, Palop A, and Periago PM. Effect of thymol and cymene on Bacillus cereus vegetative cells evaluated through the use of frequency distributions. Food Microbiology 2004; 21: 327-334. https://doi.org/10.1016/S0740-0020(03)00075-3