{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:55:08Z","timestamp":1792788908311,"version":"4.5.0"},"reference-count":95,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Bologna","award":["2025 (RFO)"],"award-info":[{"award-number":["2025 (RFO)"]}],"id":[{"id":"https:\/\/ror.org\/01111rn36","id-type":"ROR","asserted-by":"crossref"}]},{"name":"University of Bologna","award":["2024\/1424\/15"],"award-info":[{"award-number":["2024\/1424\/15"]}],"id":[{"id":"https:\/\/ror.org\/01111rn36","id-type":"ROR","asserted-by":"crossref"}]},{"name":"University of Bologna","award":["CUP=J93C23001490008"],"award-info":[{"award-number":["CUP=J93C23001490008"]}],"id":[{"id":"https:\/\/ror.org\/01111rn36","id-type":"ROR","asserted-by":"crossref"}]},{"award":["2025 (RFO)"],"award-info":[{"award-number":["2025 (RFO)"]}],"id":[{"id":"https:\/\/ror.org\/01111rn36","id-type":"ROR","asserted-by":"publisher"}]},{"award":["2024\/1424\/15"],"award-info":[{"award-number":["2024\/1424\/15"]}],"id":[{"id":"https:\/\/ror.org\/01111rn36","id-type":"ROR","asserted-by":"publisher"}]},{"award":["CUP=J93C23001490008"],"award-info":[{"award-number":["CUP=J93C23001490008"]}],"id":[{"id":"https:\/\/ror.org\/01111rn36","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Background\/Objectives: Cystitis is a common lower urinary tract infection often associated with recurrence, bladder discomfort, and increasing antimicrobial resistance. Essential oils (Cinnamomum zeylanicum, Origanum vulgare, and Thymus vulgaris) are phytocomplexes with antimicrobial, antioxidant, and smooth muscle-modulating properties. Methods: The essential oils (contained in the solid formulations) were tested against 30 samples obtained either from urine cultures or vaginal swabs, which showed either Escherichia coli or Enterococcus faecalis. Antibacterial activity was assessed by disk diffusion assay: the efficacy of ciprofloxacin was measured, as well as the efficacy of each oil, tested both alone and in combination with ciprofloxacin. Their effects on bladder function were evaluated ex vivo in isolated guinea pig bladder strips by analyzing spontaneous and KCl-induced contractility. Antioxidant activity was determined using the DPPH assay. Results: All three essential oils showed antibacterial activity against the tested clinical isolates, with different susceptibility profiles. Their combination with ciprofloxacin generally improved antibacterial responsiveness, including in isolates with reduced ciprofloxacin sensitivity. O. vulgare and T. vulgaris essential oils showed relevant spasmolytic activity against KCl-induced contraction, whereas C. zeylanicum displayed the strongest antioxidant activity and favorable modulation of spontaneous bladder contractility at low concentrations. A combined chemoinformatic and bioinformatic approach enabled the identification of potential interactions between multiple essential oil constituents and the biological pathways that ciprofloxacin is likely to target. Conclusions: These findings suggest that cinnamon, oregano and thyme essential oils may act as multitarget phytocomplexes with antibacterial, antioxidant and bladder-modulating properties. They may represent complementary candidates for cystitis management, although further mechanistic, formulation and safety studies are required.<\/jats:p>","DOI":"10.3390\/antibiotics15090909","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T13:33:42Z","timestamp":1789479222000},"page":"909","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cinnamomum zeylanicum, Origanum vulgare, and Thymus vulgaris Essential Oils in Cystitis: An Alternative\/Complementary Perspective"],"prefix":"10.3390","volume":"15","author":[{"given":"Laura Beatrice","family":"Mattioli","sequence":"first","affiliation":[{"name":"Department of Pharmacy and Biotechnology, Food Chemistry and Nutraceutical Lab, Alma Mater Studiorum-University of Bologna, 40126 Bologna, Italy"},{"name":"Interdepartmental Centre for Industrial Research in Health Sciences and Technologies\u2013CIRI Health Sciences and 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Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]},{"given":"Alberto","family":"Santini","sequence":"additional","affiliation":[{"name":"Valsambro S.r.l., via Cairoli 2, 40121 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]},{"given":"Carla","family":"Marzetti","sequence":"additional","affiliation":[{"name":"Valsambro S.r.l., via Cairoli 2, 40121 Bologna, 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Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8918-6451","authenticated-orcid":false,"given":"Diana L.","family":"Prado-Romero","sequence":"additional","affiliation":[{"name":"Department of Chemical and Pharmaceutical Sciences, University of Trieste, 34127 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Scala","sequence":"additional","affiliation":[{"name":"Biology Department, University of Naples \u201cFederico II\u201d, 80138 Naples, 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Rev. Microbiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1097\/QCO.0000000000000228","article-title":"Global Epidemiology of Urinary Tract Infections","volume":"29","author":"Tandogdu","year":"2016","journal-title":"Curr. Opin. Infect. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1111\/bju.15630","article-title":"Management of Uncomplicated Recurrent Urinary Tract Infections","volume":"129","author":"Zare","year":"2022","journal-title":"BJU Int."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1016\/j.molmed.2016.09.003","article-title":"Urinary Tract Infection: Pathogenesis and Outlook","volume":"22","author":"McLellan","year":"2016","journal-title":"Trends Mol. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1007\/s10096-024-04878-9","article-title":"Catheter Replacement in Catheter-Associated Urinary Tract Infection: Current State of Evidence","volume":"43","author":"Westgeest","year":"2024","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis. Off. Publ. Eur. Soc. Clin. Microbiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1016\/j.jiac.2021.06.006","article-title":"Complicated Urinary Tract Infection in Patients with Benign Prostatic Hyperplasia","volume":"27","author":"Choi","year":"2021","journal-title":"J. Infect. Chemother. Off. J. Jpn. Soc. Chemother."},{"key":"ref_7","first-page":"dlae214","article-title":"Bacterial Growth and Antimicrobial Resistance in Urinary Escherichia Coli Isolates among Men with Lower UTI in Swedish Primary Healthcare: Retrospective Data over a 4 Year Period","volume":"7","author":"Sundqvist","year":"2025","journal-title":"JAC-Antimicrob. Resist."},{"key":"ref_8","unstructured":"ECDC (2024). Antimicrobial Resistance in the EU\/EEA (EARS-Net)\u2014Annual Epidemiological Report 2023, ECDC."},{"key":"ref_9","unstructured":"WHO Team (2025, September 12). Antimicrobial Resistance. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/antimicrobial-resistance."},{"key":"ref_10","unstructured":"O\u2019Neill, J. (2014). Antimicrobial Resistance: Tackling a Crisis for the Health and Wealth of Nations, Wellcome Trust, HM Government."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1686","DOI":"10.1111\/j.1464-410X.2010.09445.x","article-title":"Bladder Outlet Obstruction: Progression from Inflammation to Fibrosis","volume":"106","author":"Metcalfe","year":"2010","journal-title":"BJU Int."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"127010","DOI":"10.1016\/j.micres.2022.127010","article-title":"The Urinary Microbiome and Biological Therapeutics: Novel Therapies for Urinary Tract Infections","volume":"259","author":"Kenneally","year":"2022","journal-title":"Microbiol. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1080\/19390211.2026.2615923","article-title":"Effects of a Cranberry, Probiotic, and Vitamin C Supplement on Recurrent Urinary Tract Infections in Children\u2014A Cohort Study","volume":"23","author":"Dotis","year":"2026","journal-title":"J. Diet. Suppl."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Valdivieso-Ugarte, M., Gomez-Llorente, C., Plaza-D\u00edaz, J., and Gil, \u00c1. (2019). Antimicrobial, Antioxidant, and Immunomodulatory Properties of Essential Oils: A Systematic Review. Nutrients, 11.","DOI":"10.3390\/nu11112786"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Khwaza, V., and Aderibigbe, B.A. (2025). Antibacterial Activity of Selected Essential Oil Components and Their Derivatives: A Review. Antibiotics, 14.","DOI":"10.3390\/antibiotics14010068"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1055\/a-1147-4671","article-title":"Anti-Biofilm and Virulence Factor-Reducing Activities of Essential Oils and Oil Components as a Possible Option for Bacterial Infection Control","volume":"86","author":"Reichling","year":"2020","journal-title":"Planta Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1186\/s12951-024-03006-1","article-title":"Sustainable Nanophytosome-Based Therapies against Multidrug-Resistant Escherichia Coli in Urinary Tract Infections: An In Vitro and In Vivo Study","volume":"23","author":"Wen","year":"2025","journal-title":"J. Nanobiotechnol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"9757","DOI":"10.1021\/acsomega.5c10256","article-title":"Thyme, Oregano, and Cinnamon Essential Oils: Investigating Their Molecular Mechanism of Action for the Treatment of Bacteria-Induced Cystitis","volume":"11","author":"Carosati","year":"2026","journal-title":"ACS Omega"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2323","DOI":"10.1002\/ptr.8163","article-title":"Long COVID-19 Gastrointestinal Related Disorders and Traditional Chinese Medicine: A Network Target-Based Approach","volume":"38","author":"Mattioli","year":"2024","journal-title":"Phytother. Res. PTR"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Tallarida, R.J. (1986). Manual of Pharmacologic Calculations: With Computer Programs, Springer. [1st ed.].","DOI":"10.1007\/978-1-4612-4974-0"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"D1265","DOI":"10.1093\/nar\/gkad976","article-title":"DrugBank 6.0: The DrugBank Knowledgebase for 2024","volume":"52","author":"Knox","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"D930","DOI":"10.1093\/nar\/gky1075","article-title":"ChEMBL: Towards Direct Deposition of Bioassay Data","volume":"47","author":"Mendez","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_23","unstructured":"UniProt Consortium (2025). UniProt: The Universal Protein Knowledgebase in 2025. Nucleic Acids Res., 53, D609\u2013D617."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"D672","DOI":"10.1093\/nar\/gkae909","article-title":"KEGG: Biological Systems Database as a Model of the Real World","volume":"53","author":"Kanehisa","year":"2025","journal-title":"Nucleic Acids Res."},{"key":"ref_25","unstructured":"Molecular Discovery Ltd. (2026, January 15). GRID Software. Available online: https:\/\/www.moldiscovery.com\/software\/grid\/."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1021\/jm00145a002","article-title":"A Computational Procedure for Determining Energetically Favorable Binding Sites on Biologically Important Macromolecules","volume":"28","author":"Goodford","year":"1985","journal-title":"J. Med. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2068","DOI":"10.1002\/jcc.26737","article-title":"Combining Machine Learning and Quantum Mechanics Yields More Chemically Aware Molecular Descriptors for Medicinal Chemistry Applications","volume":"42","author":"Tortorella","year":"2021","journal-title":"J. Comput. Chem."},{"key":"ref_28","unstructured":"Molecular Discovery Ltd. (2026, January 15). BioGPS Software. Available online: https:\/\/www.moldiscovery.com\/software\/biogps\/."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1002\/prot.24753","article-title":"BioGPS: Navigating Biological Space to Predict Polypharmacology, off-Targeting, and Selectivity: Identifying Structurally Similar Sites through MIFs","volume":"83","author":"Siragusa","year":"2015","journal-title":"Proteins Struct. Funct. Bioinform."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e70093","DOI":"10.1111\/jnc.70093","article-title":"A Computational Approach to Identify Novel Protein Targets Uncovers New Potential Mechanisms of Action of Mirtazapine S(+) and R(\u2212) Enantiomers in Rett Syndrome","volume":"169","author":"Roggero","year":"2025","journal-title":"J. Neurochem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"5S","DOI":"10.1016\/S0002-9343(02)01054-9","article-title":"Epidemiology of Urinary Tract Infections: Incidence, Morbidity, and Economic Costs","volume":"11","author":"Foxman","year":"2002","journal-title":"Am. J. Med."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Terlizzi, M.E., Gribaudo, G., and Maffei, M.E. (2017). UroPathogenic Escherichia Coli (UPEC) Infections: Virulence Factors, Bladder Responses, Antibiotic, and Non-Antibiotic Antimicrobial Strategies. Front. Microbiol., 8.","DOI":"10.3389\/fmicb.2017.01566"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2461","DOI":"10.1128\/IAI.73.4.2461-2468.2005","article-title":"Enterococcus Faecalis Tropism for the Kidneys in the Urinary Tract of C57BL\/6J Mice","volume":"73","author":"Kau","year":"2005","journal-title":"Infect. Immun."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4988","DOI":"10.1038\/s41467-025-60325-z","article-title":"Structures of the Escherichia Coli Type 1 Pilus during Pilus Rod Assembly and after Assembly Termination","volume":"16","author":"Bachmann","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"119541","DOI":"10.1016\/j.envpol.2022.119541","article-title":"Comprehensive Insights into Profiles and Bacterial Sources of Intracellular and Extracellular Antibiotic Resistance Genes in Groundwater","volume":"307","author":"Yang","year":"2022","journal-title":"Environ. Pollut."},{"key":"ref_36","first-page":"254ra127","article-title":"EbpA Vaccine Antibodies Block Binding of Enterococcus Faecalis to Fibrinogen to Prevent Catheter-Associated Bladder Infection in Mice","volume":"6","author":"Pinkner","year":"2014","journal-title":"Sci. Transl. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1002\/j.1875-9114.1988.tb04058.x","article-title":"Ciprofloxacin: Chemistry, Mechanism of Action, Resistance, Antimicrobial Spectrum, Pharmacokinetics, Clinical Trials, and Adverse Reactions","volume":"8","author":"LeBel","year":"1988","journal-title":"Pharmacotherapy"},{"key":"ref_38","first-page":"12","article-title":"Mechanisms of Action of and Resistance to Ciprofloxacin","volume":"82","author":"Hooper","year":"1987","journal-title":"Am. J. Med."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Shariati, A., Arshadi, M., Khosrojerdi, M.A., Abedinzadeh, M., Ganjalishahi, M., Maleki, A., Heidary, M., and Khoshnood, S. (2022). The Resistance Mechanisms of Bacteria against Ciprofloxacin and New Approaches for Enhancing the Efficacy of This Antibiotic. Front. Public Health, 10.","DOI":"10.3389\/fpubh.2022.1025633"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1080\/00325481.2019.1680052","article-title":"Treatment of Urinary Tract Infections in the Era of Antimicrobial Resistance and New Antimicrobial Agents","volume":"132","author":"Bader","year":"2020","journal-title":"Postgrad. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/j.diagmicrobio.2013.04.018","article-title":"Temporal Changes in Resistance Mechanisms in Colonizing Escherichia Coli Isolates with Reduced Susceptibility to Fluoroquinolones","volume":"76","author":"Han","year":"2013","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1128\/AAC.26.6.797","article-title":"Selection of Multiple Antibiotic Resistance by Quinolones, Beta-Lactams, and Aminoglycosides with Special Reference to Cross-Resistance between Unrelated Drug Classes","volume":"26","author":"Sanders","year":"1984","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_43","unstructured":"Antimicrobial Resistance Collaborators (2022). Global Burden of Bacterial Antimicrobial Resistance in 2019: A Systematic Analysis. Lancet, 399, 629\u2013655."},{"key":"ref_44","unstructured":"O\u2019Neill, J. (2016). Tackling Drug-Resistant Infections Globally: Final Report and Recommendations. Review on Antimicrobial Resistance, Wellcome Trust."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/S1097-2765(03)00219-3","article-title":"The Coordinated Functions of the E. Coli MutS and MutL Proteins in Mismatch Repair","volume":"12","author":"Acharya","year":"2003","journal-title":"Mol. Cell"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"28291","DOI":"10.1074\/jbc.M103148200","article-title":"Interaction of Escherichia Coli MutS and MutL at a DNA Mismatch","volume":"276","author":"Schofield","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"5887","DOI":"10.1093\/nar\/gkt278","article-title":"Crystal Structures of Escherichia Coli Exonuclease I in Complex with Single-Stranded DNA Provide Insights into the Mechanism of Processive Digestion","volume":"41","author":"Korada","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1093\/genetics\/149.1.7","article-title":"Single-Strand DNA-Specific Exonucleases in Escherichia Coli. Roles in Repair and Mutation Avoidance","volume":"149","author":"Viswanathan","year":"1998","journal-title":"Genetics"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"6106","DOI":"10.1128\/JB.182.21.6106-6113.2000","article-title":"Escherichia Coli DNA Polymerase III Tau- and Gamma-Subunit Conserved Residues Required for Activity in Vivo and in Vitro","volume":"182","author":"Walker","year":"2000","journal-title":"J. Bacteriol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"5606","DOI":"10.1074\/jbc.270.10.5606","article-title":"Escherichia Coli DNA Polymerase III Holoenzyme Subunits Alpha, Beta, and Gamma Directly Contact the Primer-Template","volume":"270","author":"Reems","year":"1995","journal-title":"J. Biol. Chem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"D439","DOI":"10.1093\/nar\/gkab1061","article-title":"AlphaFold Protein Structure Database: Massively Expanding the Structural Coverage of Protein-Sequence Space with High-Accuracy Models","volume":"50","author":"Varadi","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Erental, A., Sharon, I., and Engelberg-Kulka, H. (2012). Two Programmed Cell Death Systems in Escherichia Coli: An Apoptotic-like Death Is Inhibited by the mazEF-Mediated Death Pathway. PLoS Biol., 10.","DOI":"10.1371\/journal.pbio.1001281"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1097\/MOU.0b013e3283476ea2","article-title":"The Afferent System and Its Role in Lower Urinary Tract Dysfunction","volume":"21","author":"Daly","year":"2011","journal-title":"Curr. Opin. Urol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1016\/j.eururo.2008.06.080","article-title":"A Systematic Review and Meta-Analysis of Randomized Controlled Trials with Antimuscarinic Drugs for Overactive Bladder","volume":"54","author":"Novara","year":"2008","journal-title":"Eur. Urol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"100669","DOI":"10.1016\/j.curtheres.2022.100669","article-title":"Drugs Currently Undergoing Preclinical or Clinical Trials for the Treatment of Overactive Bladder: A Review","volume":"96","author":"Joseph","year":"2022","journal-title":"Curr. Ther. Res. Clin. Exp."},{"key":"ref_56","first-page":"e22118","article-title":"Reviving Cav1.2 as an Attractive Drug Target to Treat Bladder Dysfunction","volume":"36","author":"Yu","year":"2022","journal-title":"FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Phelps, C., Chess-Williams, R., and Moro, C. (2022). The Dependence of Urinary Bladder Responses on Extracellular Calcium Varies Between Muscarinic, Histamine, 5-HT (Serotonin), Neurokinin, Prostaglandin, and Angiotensin Receptor Activation. Front. Physiol., 13.","DOI":"10.3389\/fphys.2022.841181"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1016\/j.eururo.2006.10.034","article-title":"A Chemosensitivity Test for Superficial Bladder Cancer Based on Three-Dimensional Culture of Tumour Spheroids","volume":"51","author":"Pontones","year":"2007","journal-title":"Eur. Urol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"114147","DOI":"10.1016\/j.bcp.2020.114147","article-title":"Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) and Organ Damage: A Current Perspective","volume":"180","author":"Bindu","year":"2020","journal-title":"Biochem. Pharmacol."},{"key":"ref_60","first-page":"365","article-title":"Is A Combination of Antibiotics and Non-Steroidal Anti-Inflammatory Drugs More Beneficial Than Antibiotic Monotherapy For The Treatment of Female Acute Uncomplicated Cystitis? A Randomized Controlled Pilot Study","volume":"15","author":"Ko","year":"2018","journal-title":"Urol. J."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Okpala, O.E., Rondevaldova, J., and Kokoska, L. (2025). Anti-Inflammatory Drugs as Potential Antimicrobial Agents: A Review. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1557333"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1080\/19336950.2015.1051270","article-title":"Modulation of Nociceptive Ion Channels and Receptors via Protein-Protein Interactions: Implications for Pain Relief","volume":"9","author":"Rouwette","year":"2015","journal-title":"Channels"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Anjum, I., Mobashar, A., Jahan, S., Najm, S., Nafidi, H.-A., Bin Jardan, Y.A., and Bourhia, M. (2023). Spasmolytic and Uroprotective Effects of Apigenin by Downregulation of TGF-\u03b2 and iNOS Pathways and Upregulation of Antioxidant Mechanisms: In Vitro and In Silico Analysis. Pharmaceuticals, 16.","DOI":"10.3390\/ph16060811"},{"key":"ref_64","first-page":"577","article-title":"GC\/MS Analysis, Anti-Leishmanial and Relaxant Activity of Essential Oil of Chenopodium ambrosioides (L.) from Malakand Region","volume":"34","author":"Ali","year":"2021","journal-title":"Pak. J. Pharm. Sci."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Khan, B.A., Ahmad, S., Khan, M.K., Hosny, K.M., Bukhary, D.M., Iqbal, H., Murshid, S.S., Halwani, A.A., Alissa, M., and Menaa, F. (2022). Fabrication and Characterizations of Pharmaceutical Emulgel Co-Loaded with Naproxen-Eugenol for Improved Analgesic and Anti-Inflammatory Effects. Gels, 8.","DOI":"10.3390\/gels8100608"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1039\/C4FO00680A","article-title":"Anti-Inflammatory Activity of Cinnamon (C. zeylanicum and C. cassia) Extracts\u2014Identification of E-Cinnamaldehyde and o-Methoxy Cinnamaldehyde as the Most Potent Bioactive Compounds","volume":"6","author":"Gunawardena","year":"2015","journal-title":"Food Funct."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"\u017divkovi\u0107, M., Stanisavljevi\u0107, I., Gajovi\u0107, N., Pavlovi\u0107, S., Simovi\u0107 Markovi\u0107, B., Jovanovi\u0107, I.P., Cupara, S., Tadi\u0107, V., \u017dugi\u0107, A., and Milenkovi\u0107, M.T. (2025). Comprehensive Phytochemical Analysis and Evaluation of Antioxidant, Antimicrobial, Cytotoxic, and Immunomodulatory Activities of Commercial Cinnamon Bark Essential Oil (Cinnamomum zeylanicum L.). Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26136482"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"e47","DOI":"10.1016\/j.jss.2012.10.050","article-title":"Anti-Inflammatory Effects of Linalool in RAW 264.7 Macrophages and Lipopolysaccharide-Induced Lung Injury Model","volume":"180","author":"Huo","year":"2013","journal-title":"J. Surg. Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1016\/j.pbb.2012.11.003","article-title":"Peripherally Injected Linalool and Bergamot Essential Oil Attenuate Mechanical Allodynia via Inhibiting Spinal ERK Phosphorylation","volume":"103","author":"Kuwahata","year":"2013","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1016\/j.pbb.2010.09.020","article-title":"Intraplantar Injection of Bergamot Essential Oil Induces Peripheral Antinociception Mediated by Opioid Mechanism","volume":"97","author":"Sakurada","year":"2011","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1007\/s10787-023-01417-4","article-title":"D-Limonene Inhibits Peritoneal Adhesion Formation in Rats via Anti-Inflammatory, Anti-Angiogenic, and Antioxidative Effects","volume":"32","author":"Razazi","year":"2024","journal-title":"Inflammopharmacology"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"105743","DOI":"10.1016\/j.intimp.2019.105743","article-title":"Carvacrol Suppresses LPS-Induced pro-Inflammatory Activation in RAW 264.7 Macrophages through ERK1\/2 and NF-kB Pathway","volume":"75","author":"Somensi","year":"2019","journal-title":"Int. Immunopharmacol."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Kowalczyk, A., Przychodna, M., Sopata, S., Bodalska, A., and Fecka, I. (2020). Thymol and Thyme Essential Oil-New Insights into Selected Therapeutic Applications. Molecules, 25.","DOI":"10.3390\/molecules25184125"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.jogoh.2016.10.005","article-title":"Intended and Actual Use of Self-Medication and Alternative Products during Pregnancy by French Women","volume":"46","author":"Cabut","year":"2017","journal-title":"J. Gynecol. Obstet. Hum. Reprod."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Micucci, M., Protti, M., Aldini, R., Frosini, M., Corazza, I., Marzetti, C., Mattioli, L.B., Tocci, G., Chiarini, A., and Mercolini, L. (2020). Thymus Vulgaris L. Essential Oil Solid Formulation: Chemical Profile and Spasmolytic and Antimicrobial Effects. Biomolecules, 10.","DOI":"10.3390\/biom10060860"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1128\/JCM.36.4.990-994.1998","article-title":"Evaluation of Use of a New Chromogenic Agar in Detection of Urinary Tract Pathogens","volume":"36","author":"Samra","year":"1998","journal-title":"J. Clin. Microbiol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1788","DOI":"10.1128\/jcm.34.7.1788-1793.1996","article-title":"Evaluation of CHROMagar Orientation for Differentiation and Presumptive Identification of Gram-Negative Bacilli and Enterococcus Species","volume":"34","author":"Merlino","year":"1996","journal-title":"J. Clin. Microbiol."},{"key":"ref_78","unstructured":"Liofilchem\u00ae Chromatic Detection Non-Selective Medium for the Isolation and Differentiation of Microorganisms, Liofilchem\u00ae s.r.l."},{"key":"ref_79","unstructured":"Clinical and Laboratory Standards Institute (2013). Performance Standards for Antimicrobial Susceptibility Testing: Twenty-Third Informational Supplement, Clinical and Laboratory Standards Institute."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1002\/ptr.2105","article-title":"Evaluation of the Growth Inhibitory Activities of Triphala against Common Bacterial Isolates from HIV Infected Patients","volume":"21","author":"Srikumar","year":"2007","journal-title":"Phytother. Res. PTR"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"5102","DOI":"10.1128\/JCM.42.11.5102-5108.2004","article-title":"Antimicrobial Susceptibility Testing of Acinetobacter Spp. by NCCLS Broth Microdilution and Disk Diffusion Methods","volume":"42","author":"Swenson","year":"2004","journal-title":"J. Clin. Microbiol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1089\/jmf.2016.0154","article-title":"Newer Insights into the Antidiarrheal Effects of Acacia Catechu Willd. Extract in Guinea Pig","volume":"20","author":"Micucci","year":"2017","journal-title":"J. Med. Food"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1002\/fsn3.116","article-title":"Antimicrobial Activities of Commercial Essential Oils and Their Components against Food-Borne Pathogens and Food Spoilage Bacteria","volume":"2","author":"Mith","year":"2014","journal-title":"Food Sci. Nutr."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Percie du Sert, N., Hurst, V., Ahluwalia, A., Alam, S., Avey, M.T., Baker, M., Browne, W.J., Clark, A., Cuthill, I.C., and Dirnagl, U. (2020). The ARRIVE Guidelines 2.0: Updated Guidelines for Reporting Animal Research. PLoS Biol., 18.","DOI":"10.1371\/journal.pbio.3000410"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1089\/jmf.2015.0072","article-title":"Hibiscus sabdariffa L. Flowers and Olea europea L. Leaves Extract-Based Formulation for Hypertension Care: In Vitro Efficacy and Toxicological Profile","volume":"19","author":"Micucci","year":"2016","journal-title":"J. Med. Food"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Panaro, M.A., Budriesi, R., Calvello, R., Cianciulli, A., Mattioli, L.B., Corazza, I., Rotondo, N.P., Porro, C., Lamonaca, A., and Ferraro, V. (2024). Lentil Waste Extracts for Inflammatory Bowel Disease (IBD) Symptoms Control: Anti-Inflammatory and Spasmolytic Effects. Nutrients, 16.","DOI":"10.3390\/nu16193327"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"2540051","DOI":"10.1142\/S0219519425400512","article-title":"Biomechanical Characterization of Spontaneous and Induced Motility in Small Animals\u2019 Gastrointestinal Tissue for Human Nutraceutical and Pharmaceutical Purposes","volume":"26","author":"Mattioli","year":"2025","journal-title":"J. Mech. Med. Biol."},{"key":"ref_88","unstructured":"Motulsky, H. (2007). PraphPad PRISM Version 5.0\u2014Statistics Guide, GraphPad Software, Inc."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Motulsky, H., Christopoulos, A., Motulsky, H., and Christopoulos, A. (2004). Fitting Models to Biological Data Using Linear and Nonlinear Regression: A Practical Guide to Curve Fitting, Oxford University Press.","DOI":"10.1093\/oso\/9780195171792.001.0001"},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Mattioli, L.B., Corazza, I., Budriesi, R., Hrelia, S., Malaguti, M., Caliceti, C., Amoroso, R., Maccallini, C., Crupi, P., and Clodoveo, M.L. (2024). From Waste to Health: Olive Mill Wastewater for Cardiovascular Disease Prevention. Nutrients, 16.","DOI":"10.3390\/nu16172986"},{"key":"ref_91","first-page":"120","article-title":"Chemical Profile and Biological Activities of Cedrelopsis grevei H. Baillon Bark Essential Oil","volume":"152","author":"Tardugno","year":"2018","journal-title":"Plant Biosyst.\u2014Int. J. Deal. Asp. Plant Biol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/1758-2946-5-3","article-title":"UniChem: A Unified Chemical Structure Cross-Referencing and Identifier Tracking System","volume":"5","author":"Chambers","year":"2013","journal-title":"J. Cheminform."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1080\/1040841X.2024.2313024","article-title":"Antibiotic Resistance: A Global Crisis, Problems and Solutions","volume":"50","author":"Aggarwal","year":"2024","journal-title":"Crit. Rev. Microbiol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"106801","DOI":"10.1016\/j.fitote.2025.106801","article-title":"Human Cell Toxicity and in Vivo Bioavailability of Therapeutic Essential Oils\u2014A Review","volume":"186","author":"Jenitha","year":"2025","journal-title":"Fitoterapia"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"118180","DOI":"10.1016\/j.jep.2024.118180","article-title":"Essential Oils for Clinical Aromatherapy: A Comprehensive Review","volume":"330","author":"Vora","year":"2024","journal-title":"J. Ethnopharmacol."}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/15\/9\/909\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T04:12:56Z","timestamp":1790136776000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/15\/9\/909"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,15]]},"references-count":95,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["antibiotics15090909"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics15090909","relation":{},"ISSN":["2079-6382"],"issn-type":[{"value":"2079-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,15]]}}}