{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T03:44:18Z","timestamp":1790480658466,"version":"4.1.0"},"reference-count":50,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,5,9]],"date-time":"2025-05-09T00:00:00Z","timestamp":1746748800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Research, Innovation, and Digitization, CNCS-UEFISCDI","award":["PN-III-P4-PCE-2021-1692, within PNCDI III"],"award-info":[{"award-number":["PN-III-P4-PCE-2021-1692, within PNCDI III"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Solanum macrocarpon L. has been studied for its neuroprotective potential and memory-enhancing properties. Research suggests that bioactive compounds, including flavonoids, alkaloids, and phenolics, contribute to its cognitive benefits. These compounds may help protect against oxidative stress, neuroinflammation, and cholinergic dysfunction factors in memory impairment. This study was undertaken to investigate the effects of S. macrocarpon ethanolic leaf extract (SMEE) on the memory, anxiety-like behavior, and brain antioxidant status of scopolamine (SCOP, 100 \u03bcM)-induced amnesic zebrafish (Danio rerio) and thus to understand its possible mechanism of action. Methods: Adult zebrafish (n = 100) were divided into two cohorts (\u00b1SCOP) of five experimental groups: (I) control; (II) galantamine (GAL, 1 mg\/L), serving as a positive control for both behavioral and biochemical assessments; (III\u2013V) three groups treated with SMEE (1, 3, and 6 mg\/L); (VI) scopolamine (SCOP, 100 \u03bcM); (VII) SCOP (100 \u03bcM) combined with GAL (1 mg\/L); and (VIII\u2013X) three groups treated with SCOP (100 \u03bcM) plus SMEE (1, 3, and 6 mg\/L). The treatment lasted 23 days and amnesia was induced by a single dose of SCOP (100 \u03bcM) before testing. Results: The phenolic characterization from the samples was performed by using HPLC-PDA chromatography. Following HPLC analysis, an in silico pharmacokinetic evaluation was conducted using the ADMET model to investigate the pharmacological and toxicological profiles of the identified compounds. Spatial memory was evaluated through the Y-maze and novel object recognition (NOR) tests, while anxiety-like behavior was assessed using the novel tank diving test (NTT), novel approach test (NAT), and light\u2013dark test (LDT). The zebrafish were euthanized, and homogenates of isolated brain samples were assayed for acetylcholinesterase (AChE) activity and brain antioxidant markers. The HPLC analysis revealed that the main major compounds in the extract were chlorogenic acid and rutin, both recognized for their significant antioxidant properties. Conclusions: SMEE enhanced memory by inhibiting AChE, alleviated SCOP-induced anxiety-like behavior, and significantly decreased oxidative stress markers. These findings support the potential role of SMEE in counteracting SCOP-induced cognitive and behavioral dysfunctions, related to dementia conditions.<\/jats:p>","DOI":"10.3390\/ph18050706","type":"journal-article","created":{"date-parts":[[2025,5,9]],"date-time":"2025-05-09T11:25:53Z","timestamp":1746789953000},"page":"706","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Solanum\u00a0macrocarpon L. Ethanolic Leaf Extract Exhibits Neuroprotective and Anxiolytic Effects in Scopolamine-Induced Amnesic Zebrafish Model"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3103-9728","authenticated-orcid":false,"given":"Ion","family":"Brinza","sequence":"first","affiliation":[{"name":"Faculty of Sciences, Lucian Blaga University of Sibiu, 550024 Sibiu, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corina","family":"Guliev","sequence":"additional","affiliation":[{"name":"Faculty of Sciences, Lucian Blaga University of Sibiu, 550024 Sibiu, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5485-1132","authenticated-orcid":false,"given":"Ibukun Oluwabukola","family":"Oresanya","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy, Gazi University, 06330 Ankara, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4115-7509","authenticated-orcid":false,"given":"Hasya Nazli","family":"Gok","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy, Gazi University, 06330 Ankara, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7379-5436","authenticated-orcid":false,"given":"Ilkay Erdogan","family":"Orhan","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy, Lokman Hekim University, 06510 Ankara, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6981-4174","authenticated-orcid":false,"given":"Lucian","family":"Hritcu","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Biology, Alexandru Ioan Cuza University of Iasi, 700506 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Safiri, S., Ghaffari Jolfayi, A., Fazlollahi, A., Morsali, S., Sarkesh, A., Daei Sorkhabi, A., Golabi, B., Aletaha, R., Motlagh Asghari, K., and Hamidi, S. (2024). Alzheimer\u2019s Disease: A Comprehensive Review of Epidemiology, Risk Factors, Symptoms Diagnosis, Management, Caregiving, Advanced Treatments and Associated Challenges. Front. Med., 11.","DOI":"10.3389\/fmed.2024.1474043"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Xu Lou, I., Ali, K., and Chen, Q. (2023). Effect of Nutrition in Alzheimer\u2019s Disease: A Systematic Review. Front. Neurosci., 17.","DOI":"10.3389\/fnins.2023.1147177"},{"key":"ref_3","first-page":"1","article-title":"Recent Advances in Alzheimer\u2019s Disease: Mechanisms, Clinical Trials and New Drug Development Strategies","volume":"9","author":"Zhang","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.mito.2023.05.007","article-title":"Mitochondrial Dysfunction and Oxidative Stress in Alzheimer\u2019s Disease, and Parkinson\u2019s Disease, Huntington\u2019s Disease and Amyotrophic Lateral Sclerosis-An Updated Review","volume":"71","author":"Alqahtani","year":"2023","journal-title":"Mitochondrion"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Madnani, R.S. (2023). Alzheimer\u2019s Disease: A Mini-Review for the Clinician. Front. Neurol., 14.","DOI":"10.3389\/fneur.2023.1178588"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Popovici, L.F., Brinza, I., Gatea, F., Badea, G.I., Vamanu, E., Oancea, S., and Hritcu, L. (2025). Enhancement of Cognitive Benefits and Anti-Anxiety Effects of Phytolacca Americana Fruits in a Zebrafish (Danio Rerio) Model of Scopolamine-Induced Memory Impairment. Antioxidants, 14.","DOI":"10.3390\/antiox14010097"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Sakai, C., Ijaz, S., and Hoffman, E.J. (2018). Zebrafish Models of Neurodevelopmental Disorders: Past, Present, and Future. Front. Mol. Neurosci., 11.","DOI":"10.3389\/fnmol.2018.00294"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1136\/jmedgenet-2018-105358","article-title":"Use of Zebrafish Models to Investigate Rare Human Disease","volume":"55","author":"Adamson","year":"2018","journal-title":"J. Med. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"6","DOI":"10.5734\/JGM.2024.21.1.6","article-title":"Using Zebrafish as an Animal Model for Studying Rare Neurological Disorders: A Human Genetics Perspective","volume":"21","author":"Don","year":"2024","journal-title":"J. Genet. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.neuroscience.2019.08.034","article-title":"Zebrafish as a Model of Neurodevelopmental Disorders","volume":"445","author":"Genario","year":"2020","journal-title":"Neuroscience"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1007\/s00580-024-03556-8","article-title":"Spermicidal and Antioxidant Potency of Solanum macrocarpon L. (African Eggplant) Leaf Ethanol Extract in Albino Rats","volume":"33","author":"Ezechukwu","year":"2024","journal-title":"Comp. Clin. Path"},{"key":"ref_12","first-page":"1595","article-title":"Phytochemical Screening, Nutritional and Toxicological Analyses of Leaves and Fruits of Solanum Macrocarpon Linn (Solanaceae) in Cotonou (Benin)","volume":"3","author":"Dougnon","year":"2012","journal-title":"Food Nutr. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"28","DOI":"10.11648\/j.ab.20130102.14","article-title":"Effect of Solanum Macrocarpon Fruit on Haematology, Hepatic and Renal Function","volume":"1","author":"Majesty","year":"2013","journal-title":"Adv. Biochem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"43","DOI":"10.5897\/JPP2019.0543","article-title":"Phytochemistry, Acute Toxicity and Blood Profile of Albino Rats Treated with Fruit Extract of Solanum Macrocarpon","volume":"11","author":"Chidiebere","year":"2019","journal-title":"J. Pharmacogn. Phytother."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Bouabdallah, S., Brinza, I., Boiangiu, R.S., Ibrahim, M.H., Honceriu, I., Al-Maktoum, A., Cioanca, O., Hancianu, M., Amin, A., and Ben-Attia, M. (2024). The Effect of a Tribulus-Based Formulation in Alleviating Cholinergic System Impairment and Scopolamine-Induced Memory Loss in Zebrafish (Danio Rerio): Insights from Molecular Docking and In Vitro\/In Vivo Approaches. Pharmaceuticals, 17.","DOI":"10.3390\/ph17020200"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1007\/s10695-023-01185-6","article-title":"Betanin Mitigates Scopolamine-Induced Cognitive Impairment by Restoring Cholinergic Function, Boosting Brain Antioxidative Status, and Increasing BDNF Level in the Zebrafish Model","volume":"49","author":"Thawkar","year":"2023","journal-title":"Fish. Physiol. Biochem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"300060520922649","DOI":"10.1177\/0300060520922649","article-title":"Effect of Solanum Macrocarpon Linn Leaf Aqueous Extract on the Brain of an Alloxan-Induced Rat Model of Diabetes","volume":"48","author":"Okesola","year":"2020","journal-title":"J. Int. Med. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"20190256","DOI":"10.1515\/jbcpp-2019-0256","article-title":"Solanum Leaves Extracts Exhibit Antioxidant Properties and Inhibit Monoamine Oxidase and Acetylcholinesterase Activities (In Vitro) in Drosophila Melanogaster","volume":"31","author":"Ogunsuyi","year":"2020","journal-title":"J. Basic. Clin. Physiol. Pharmacol."},{"key":"ref_19","first-page":"190","article-title":"Antioxidant Activities and Inhibitory Action of Solanum Macrocarpon and Hibiscus Esculentus Phenolic Containing Leaf Extracts against Lipid Oxidation","volume":"2","author":"Salawu","year":"2013","journal-title":"Int. J. Med. Plants Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3905","DOI":"10.2174\/0929867329666220816154634","article-title":"Chlorogenic Acid: A Dietary Phenolic Acid with Promising Pharmacotherapeutic Potential","volume":"30","author":"Singh","year":"2022","journal-title":"Curr. Med. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Nguyen, V., Taine, E.G., Meng, D., Cui, T., and Tan, W. (2024). Chlorogenic Acid: A Systematic Review on the Biological Functions, Mechanistic Actions, and Therapeutic Potentials. Nutrients, 16.","DOI":"10.3390\/nu16070924"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/bs.apha.2019.12.002","article-title":"Pharmacological Action and Potential Targets of Chlorogenic Acid","volume":"87","author":"Miao","year":"2020","journal-title":"Adv. Pharmacol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"106163","DOI":"10.1016\/j.phrs.2022.106163","article-title":"Rutin Ameliorates Inflammation and Improves Metabolic Function: A Comprehensive Analysis of Scientific Literature","volume":"178","author":"Muvhulawa","year":"2022","journal-title":"Pharmacol. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1080\/10408398.2020.1829541","article-title":"The Anticancer Potential of the Dietary Polyphenol Rutin: Current Status, Challenges, and Perspectives","volume":"62","author":"Farha","year":"2022","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"26","DOI":"10.21608\/mjvm.2024.341806","article-title":"Rutin: Chemical Properties, Pharmacokinetic Properties and Biological Activities","volume":"4","author":"Madkour","year":"2024","journal-title":"Matrouh J. Vet. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"177013","DOI":"10.1016\/j.ejphar.2024.177013","article-title":"Rhoifolin, Baicalein 5,6-Dimethyl Ether and Agathisflavone Prevent Amnesia Induced in Scopolamine Zebrafish (Danio Rerio) Model by Increasing the MRNA Expression of Bdnf, Npy, Egr-1, Nfr2\u03b1, and Creb1 Genes","volume":"984","author":"Brinza","year":"2024","journal-title":"Eur. J. Pharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/srep09748","article-title":"Scopolamine Effects on Functional Brain Connectivity: A Pharmacological Model of Alzheimer\u2019s Disease","volume":"5","author":"Bajo","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-017-15374-w","article-title":"Establishing Zebrafish as a Model to Study the Anxiolytic Effects of Scopolamine","volume":"7","author":"Hamilton","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1007\/s11101-016-9477-x","article-title":"Scopolamine: A Journey from the Field to Clinics","volume":"16","author":"Ullrich","year":"2016","journal-title":"Phytochem. Rev."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"7725","DOI":"10.1080\/07391102.2022.2124194","article-title":"Phytochemicals from African Eggplants (Solanum macrocarpon L.) and Black Nightshade (Solanum nigrum L.) Leaves as Acetylcholinesterase Inhibitors: An in-Silico Study","volume":"41","author":"Ogunsuyi","year":"2023","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e049605","DOI":"10.1002\/alz.049605","article-title":"In Vitro and in Silico Investigation of Cholinesterase Inhibition and Anti-Radical Properties of Solanum Macrocarpon Leaf Extracts: A Preliminary Anti-Alzheimer\u2019s Study","volume":"17","author":"Idowu","year":"2021","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_32","first-page":"33","article-title":"Solanum Anomalum Leaf Extract and Fractions Attenuate Oxidative Stress and Liver Injuries in Alloxan-Induced Diabetic Rats","volume":"12","author":"Etuk","year":"2023","journal-title":"Biol. Med. Nat. Prod. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Osukoya, O.A., Ajiboye, B.O., Oyinloye, B.E., Owero-ozeze, O.S., Ojo, O.A., and Kappo, P.A. (2022). Aqueous Extract of Solanum Macrocapon Linn Leaf Abate Diabetic Cardiomyopathy by Attenuating Oxidative Stress and Inflammation in Rats. J. Food Biochem., 46.","DOI":"10.1111\/jfbc.14172"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Ekin, S., Kiziltas, H., Bayramoglu Akkoyun, M., Ekin, H.N., Yildirim, S., Oto, G., Akbas, E., Deliorman Orhan, D., and Ozgokce, F. (2019). Nephroprotective Effect of Ferulago Angulata Flowers on N-Nitrosodimethylamine-Induced Nephrotoxicity in Rats and Its Phytochemical Profile. J. Food Biochem., 43.","DOI":"10.1111\/jfbc.13030"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4066","DOI":"10.1021\/acs.jmedchem.5b00104","article-title":"PkCSM: Predicting-Molecule Pharmacokinetic and Toxicity Properties Using Graph-Based Signatures","volume":"58","author":"Pires","year":"2015","journal-title":"J. Med. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"W422","DOI":"10.1093\/nar\/gkae236","article-title":"ADMETlab 3.0: An Updated Comprehensive Online ADMET Prediction Platform Enhanced with Broader Coverage, Improved Performance, API Functionality and Decision Support","volume":"52","author":"Fu","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1007\/s10593-014-1496-1","article-title":"Prediction of the Biological Activity Spectra of Organic Compounds Using the Pass Online Web Resource","volume":"50","author":"Filimonov","year":"2014","journal-title":"Chem. Heterocycl. Compd."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Bate, S.T., and Clark, R.A. (2014). The Design and Statistical Analysis of Animal Experiments, Cambridge University Press.","DOI":"10.1017\/CBO9781139344319"},{"key":"ref_39","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_40","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-1-60761-953-6_1","article-title":"Video-Aided Analysis of Zebrafish Locomotion and Anxiety-Related Behavioral Responses","volume":"Volume 51","author":"Cachat","year":"2011","journal-title":"Neuromethods"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.pbb.2019.01.006","article-title":"The Light-Dark Task in Zebrafish Confuses Two Distinct Factors: Interaction between Background Shade and Illumination Level Preference","volume":"179","author":"Facciol","year":"2019","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.nlm.2012.09.008","article-title":"Y-Maze Memory Task in Zebrafish (Danio Rerio): The Role of Glutamatergic and Cholinergic Systems on the Acquisition and Consolidation Periods","volume":"98","author":"Bortolotto","year":"2012","journal-title":"Neurobiol. Learn. Mem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1007\/s00213-017-4532-x","article-title":"Short- and Long-Term Effects of Nicotine and the Histone Deacetylase Inhibitor Phenylbutyrate on Novel Object Recognition in Zebrafish","volume":"234","author":"Faillace","year":"2017","journal-title":"Psychopharmacology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/0006-2952(61)90145-9","article-title":"A New and Rapid Colorimetric Determination of Acetylcholinesterase Activity","volume":"7","author":"Ellman","year":"1961","journal-title":"Biochem. Pharmacol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/0003-2697(76)90527-3","article-title":"A Rapid and Sensitive Method for the Quantitation of Microgram Quantities of Protein Utilizing the Principle of Protein-Dye Binding","volume":"72","author":"Bradford","year":"1976","journal-title":"Anal. Biochem."},{"key":"ref_46","unstructured":"Artenie, V., Ungureanu, E., and Negur\u0103, A.M. (2008). Metode de Investigare a Metabolismului Glucidic \u0218i Lipidic, Editura Pim."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/0003-2697(72)90132-7","article-title":"Colorimetric Assay of Catalase","volume":"47","author":"Sinha","year":"1972","journal-title":"Anal. Biochem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"405","DOI":"10.3177\/jnsv.22.405","article-title":"Glutathione Peroxidase Activity in Tissues of Vitamin E-Deficient Mice","volume":"22","author":"Fukuzawa","year":"1976","journal-title":"J. Nutr. Sci. Vitaminol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1179\/135100009X392601","article-title":"Protein Carbonylation: Avoiding Pitfalls in the 2,4-Dinitrophenylhydrazine Assay","volume":"14","author":"Luo","year":"2009","journal-title":"Redox Rep."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/0003-2697(79)90738-3","article-title":"Assay for Lipid Peroxides in Animal Tissues by Thiobarbituric Acid Reaction","volume":"95","author":"Ohkawa","year":"1979","journal-title":"Anal. Biochem."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/5\/706\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:30:25Z","timestamp":1760031025000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/5\/706"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,9]]},"references-count":50,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2025,5]]}},"alternative-id":["ph18050706"],"URL":"https:\/\/doi.org\/10.3390\/ph18050706","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,9]]}}}