{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T19:17:31Z","timestamp":1787944651325,"version":"build-2784847793"},"reference-count":71,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Scientific Research Projects Coordination Unit of the University of Health Sciences","award":["BAP-2024\/122"],"award-info":[{"award-number":["BAP-2024\/122"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives:\u00a0Berberis species are recognized for their ethnomedicinal importance and phytochemical richness associated with antidiabetic activity. Although B. crataegina is widely distributed in the Turkish flora and has a history of traditional use, its phytochemical properties and biological activities remain less extensively investigated than those of other Berberis species. This study aimed to comparatively evaluate the phytochemical profiles, in vitro antidiabetic potential, and cytoprotective effects of extracts prepared from different parts of B. crataegina in a high-glucose-induced SH-SY5Y cell-based model of diabetic neuropathy. Methods: Crude hydroethanolic extracts (70% ethanol) were prepared from the leaves, flowers, shoots, roots, and fresh fruits of B. crataegina collected from K\u0131z\u0131lcahamam, Ankara, T\u00fcrkiye. The total phenolic and flavonoid contents, antioxidant capacities and \u03b1-glucosidase inhibitory activities of leaf, flower, shoot, root, and fruit extracts were determined. The cytoprotective effects of the crude extracts were evaluated in a high-glucose-induced SH-SY5Y cell model. The metabolomic profiles of the extracts were comparatively analyzed using liquid chromatography\u2013quadrupole time-of-flight mass spectrometry (LC-QTOF-MS). The most active fruit extract was fractionated by reversed-phase vacuum liquid chromatography (RP-VLC), and the phytochemical contents and \u03b1-glucosidase inhibitory activities of the fractions were evaluated. The major phenolic compounds in the most active fruit extract were quantitatively determined using high-performance liquid chromatography\u2013diode array detection (HPLC-DAD). The relationships between metabolites and biological activities were investigated through correlation analysis. Results: The fruit extract was distinguished by its \u03b1-glucosidase inhibitory activity, total phenolic content, antioxidant capacity, and cytoprotective effect in the high-glucose-induced SH-SY5Y cell model. It showed no marked cytotoxicity at concentrations ranging from 25 to 400 \u00b5g\/mL and, at 25 \u00b5g\/mL, attenuated the high-glucose-induced reduction in cell viability, restoring viability to a level close to that of the normal control. Untargeted metabolomic analysis identified 191 metabolites detected in at least two crude extracts, while the metabolites detected exclusively in the fruit extract were predominantly flavonoids and flavonoid glycosides. Fractionation showed that \u03b1-glucosidase inhibitory activity was mainly concentrated in the medium-polarity fractions; however, none of the fractions reached the activity level of the crude extract. Chlorogenic acid, rutin, caffeic acid, protocatechuic acid, quercetin, and quercetin-3-O-glucoside were detected and quantified in the fruit extract by HPLC-DAD. Correlation analysis indicated that the observed biological activities may be associated with phenolic acids, flavonoids, and other polyphenolic metabolites. Conclusions: The fruit extract of B. crataegina showed promising \u03b1-glucosidase inhibitory activity and cytoprotective effects in the high-glucose-induced SH-SY5Y cell model. The findings suggest that these effects may arise from the combined contribution of multiple constituents within a polyphenolic matrix rather than from a single compound; however, synergistic interactions were not experimentally demonstrated. These results support further evaluation of the fruit extract through mechanistic, in vivo, and standardization studies.<\/jats:p>","DOI":"10.3390\/ph19091365","type":"journal-article","created":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T18:33:52Z","timestamp":1787942032000},"page":"1365","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Untargeted Metabolomic and Phytochemical Profiling of Berberis crataegina DC. Plant Parts: Antidiabetic Potential and Cytoprotection in High-Glucose-Exposed SH-SY5Y Cells"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-2781-7682","authenticated-orcid":false,"given":"Yi\u011fit","family":"Erkmen","sequence":"first","affiliation":[{"name":"Department of Pharmacognosy, Gulhane Faculty of Pharmacy, University of Health Sciences, 06108 Ankara, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"given":"Zekiye Ceren","family":"Ar\u0131tuluk Ayd\u0131n","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Botany, Faculty of Pharmacy, Hacettepe University, 06100 Ankara, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1076-1300","authenticated-orcid":false,"given":"Engin","family":"Ko\u00e7ak","sequence":"additional","affiliation":[{"name":"Department of Analytical Chemistry, Gulhane Faculty of Pharmacy, University of Health Sciences, 06108 Ankara, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4115-7509","authenticated-orcid":false,"given":"Hasya Nazl\u0131","family":"G\u00f6k","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy, Gazi University, 06330 Ankara, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7337-6215","authenticated-orcid":false,"given":"Emirhan","family":"Nemutlu","sequence":"additional","affiliation":[{"name":"Department of Analytical Chemistry, Faculty of Pharmacy, Hacettepe University, 06100 Ankara, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7482-0429","authenticated-orcid":false,"given":"Merve","family":"Y\u00fczba\u015f\u0131o\u011flu Baran","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Gulhane Faculty of Pharmacy, University of Health Sciences, 06108 Ankara, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1212\/01.CON.0000411568.34085.3e","article-title":"Diabetic Neuropathy","volume":"18","author":"Smith","year":"2012","journal-title":"Continuum"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/s41572-019-0092-1","article-title":"Diabetic Neuropathy","volume":"5","author":"Feldman","year":"2019","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2337\/db20182-1","article-title":"Diagnosis and Management of Diabetic Foot Complications","volume":"2018","author":"Boulton","year":"2018","journal-title":"ADA Clin. Compend."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"296","DOI":"10.4239\/wjd.v6.i2.296","article-title":"Prediabetes Diagnosis and Treatment: A Review","volume":"6","author":"Bansal","year":"2015","journal-title":"World J. Diabetes"},{"key":"ref_5","first-page":"210","article-title":"Do\u011fal Kaynaklar\u0131n Diyabetik N\u00f6ropati Tedavisindeki Rol\u00fc","volume":"50","author":"Erkmen","year":"2026","journal-title":"Ank. Univ. Eczaci. Fak. Derg."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Kashtoh, H., and Baek, K.-H. (2022). Recent Updates on Phytoconstituent Alpha-Glucosidase Inhibitors: An Approach towards the Treatment of Type Two Diabetes. Plants, 11.","DOI":"10.3390\/plants11202722"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Salehi, B., Ata, A., Anil Kumar, N.V., Sharopov, F., Ram\u00edrez-Alarc\u00f3n, K., Ruiz-Ortega, A., Abdulmajid Ayatollahi, S., Valere Tsouh Fokou, P., Kobarfard, F., and Amiruddin Zakaria, Z. (2019). Antidiabetic Potential of Medicinal Plants and Their Active Components. Biomolecules, 9.","DOI":"10.3390\/biom9100551"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Blahova, J., Martiniakova, M., Babikova, M., Kovacova, V., Mondockova, V., and Omelka, R. (2021). Pharmaceutical Drugs and Natural Therapeutic Products for the Treatment of Type 2 Diabetes Mellitus. Pharmaceuticals, 14.","DOI":"10.3390\/ph14080806"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/j.jtcme.2017.08.012","article-title":"An Update on Natural Compounds in the Remedy of Diabetes Mellitus: A Systematic Review","volume":"8","author":"Choudhury","year":"2018","journal-title":"J. Tradit. Complement. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"143","DOI":"10.4103\/0973-3930.57344","article-title":"A Brief Review of in vitro Models of Diabetic Neuropathy","volume":"29","author":"Hattangady","year":"2009","journal-title":"Int. J. Diabetes Dev. Ctries."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Governa, P., Baini, G., Borgonetti, V., Cettolin, G., Giachetti, D., Magnano, A., Miraldi, E., and Biagi, M. (2018). Phytotherapy in the Management of Diabetes: A Review. Molecules, 23.","DOI":"10.3390\/molecules23010105"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1007\/s11101-021-09773-1","article-title":"A Review of Alpha-Glucosidase Inhibitors from Plants as Potential Candidates for the Treatment of Type-2 Diabetes","volume":"21","author":"Dirir","year":"2022","journal-title":"Phytochem. Rev."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"AL-Ishaq, R.K., Abotaleb, M., Kubatka, P., Kajo, K., and B\u00fcsselberg, D. (2019). Flavonoids and Their Anti-Diabetic Effects: Cellular Mechanisms and Effects to Improve Blood Sugar Levels. Biomolecules, 9.","DOI":"10.3390\/biom9090430"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Belwal, T., Bisht, A., Devkota, H.P., Ullah, H., Khan, H., Pandey, A., Bhatt, I.D., and Echeverr\u00eda, J. (2020). Phytopharmacology and Clinical Updates of Berberis Species Against Diabetes and Other Metabolic Diseases. Front. Pharmacol., 11.","DOI":"10.3389\/fphar.2020.00041"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e202400911","DOI":"10.1002\/cbdv.202400911","article-title":"Genus Berberis: A Comprehensive and Updated Review on Ethnobotanical Uses, Phytochemistry and Pharmacological Activities","volume":"21","author":"Saleem","year":"2024","journal-title":"Chem. Biodivers."},{"key":"ref_16","unstructured":"Tuzlac\u0131, E. (2011). T\u00fcrkiye\u2019nin Yabani Besin Bitkileri ve Ot Yemekleri, Alfa Yay\u0131nlar\u0131."},{"key":"ref_17","unstructured":"Tuzlac\u0131, E. (2016). T\u00fcrkiye Bitkileri Geleneksel \u0130la\u00e7 Rehberi, \u0130stanbul T\u0131p Kitabevleri."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Emre, G., Dogan, A., Haznedaroglu, M.Z., Senkardes, I., Ulger, M., Satiroglu, A., Can Emmez, B., and Tugay, O. (2021). An Ethnobotanical Study of Medicinal Plants in Mersin (Turkey). Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.664500"},{"key":"ref_19","first-page":"63","article-title":"Traditional Medicinal Plants Used in Pinarbasi Area (Kayseri-Turkey)","volume":"2","author":"Koyuncu","year":"2005","journal-title":"Turk. J. Pharm. Sci."},{"key":"ref_20","first-page":"34","article-title":"Traditional Uses of Medicinal Plants in Erzincan Province, T\u00fcrkiye","volume":"48","author":"Korkmaz","year":"2023","journal-title":"Ank. Univ. Eczaci. Fak. Derg."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Dogan, A. (2024). Cultural Use and the Knowledge of Ethnomedicinal Plants in the P\u00fcl\u00fcm\u00fcr (Dersim-Tunceli) Region. Plants, 13.","DOI":"10.3390\/plants13152104"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/S0378-8741(01)00387-7","article-title":"Berberis crataegina DC. Root Exhibits Potent Anti-Inflammatory, Analgesic and Febrifuge Effects in Mice and Rats","volume":"79","year":"2002","journal-title":"J. Ethnopharmacol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/s40199-015-0108-7","article-title":"The Fruit Extract of Berberis crataegina DC: Exerts Potent Antioxidant Activity and Protects DNA Integrity","volume":"23","author":"Charehsaz","year":"2015","journal-title":"DARU J. Pharm. Sci."},{"key":"ref_24","first-page":"8908301","article-title":"Bioactive Characteristics of Wild Berberis vulgaris and Berberis crataegina Fruits","volume":"2020","author":"Dertli","year":"2020","journal-title":"J. Chem."},{"key":"ref_25","first-page":"178","article-title":"Evaluation of the Potential Antibacterial Activity of Berberis crataegina DC.: With Focus on Quorum Sensing Inhibition of Chromobacterium Violaceum ATCC 12472","volume":"47","author":"Arin","year":"2022","journal-title":"Ank. Univ. Eczaci. Fak. Derg."},{"key":"ref_26","first-page":"100020","article-title":"Bioactive Components, Antioxidant Capacity, and Antimicrobial Activity of Berberis crataegina Fruit","volume":"2","author":"Ercan","year":"2024","journal-title":"Pharmacol. Res.-Nat. Prod."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e202402591","DOI":"10.1002\/cbdv.202402591","article-title":"Investigation of Antioxidant, Antibacterial, and Anticancer Activities, and Molecular Modeling Studies of Berberis crataegina Fruit Extract","volume":"22","author":"Onem","year":"2025","journal-title":"Chem. Biodivers."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"116795","DOI":"10.1016\/j.trac.2022.116795","article-title":"Metabolomics Analysis Insight into Medicinal Plant Science","volume":"157","author":"Waris","year":"2022","journal-title":"TrAC Trends Anal. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"8","DOI":"10.4103\/0973-7847.125517","article-title":"Phytochemistry and Pharmacology of Berberis Species","volume":"8","author":"Saeidnia","year":"2014","journal-title":"Pharmacogn. Rev."},{"key":"ref_30","first-page":"3071","article-title":"Mineral Elements, Phenolics and Organic Acids of Leaves and Fruits from Berberis crataegina DC","volume":"23","year":"2011","journal-title":"Asian J. Chem."},{"key":"ref_31","unstructured":"Ko\u015far, M. (1999). T\u00fcrkiye\u2019de Yeti\u015fen Berberis L. T\u00fcrlerinin Alkaloitleri. [Master\u2019s Thesis, Anadolu \u00dcniversitesi Sa\u011fl\u0131k Bilimleri Enstit\u00fcs\u00fc]."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Och, A., Olech, M., B\u0105k, K., Kanak, S., Cwener, A., Cie\u015bla, M., and Nowak, R. (2023). Evaluation of the Antioxidant and Anti-Lipoxygenase Activity of Berberis vulgaris L. Leaves, Fruits, and Stem and Their LC MS\/MS Polyphenolic Profile. Antioxidants, 12.","DOI":"10.20944\/preprints202306.1280.v1"},{"key":"ref_33","first-page":"1","article-title":"A Glance at Berberis integerimma Pharmacological Effects and Its Active Constituents","volume":"6","author":"Moein","year":"2020","journal-title":"Trends Pharm. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e00868","DOI":"10.1002\/cbdv.202500868","article-title":"Effects of Selected Medicinal Plants on Enzymatic Targets Related to Diabetes Mellitus and Obesity","volume":"22","author":"Pekacar","year":"2025","journal-title":"Chem. Biodivers."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Zhaleh, N., Sharifi, M., Samari, E., Halvagar, M.R., and Zeidi, S.H. (2025). A Comparative Study of Alkaloid and Phenolic Compounds in Different Organs and Tissues of Berberis integerrima. PLoS ONE, 20.","DOI":"10.1371\/journal.pone.0321255"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1186\/s13765-024-00884-9","article-title":"Development and Application of a High-Performance Liquid Chromatography Diode-Array Detection (HPLC\u2013DAD) Method for the Simultaneous Quantification of Phenolic Compounds in the Aerial Part of Glehnia Littoralis","volume":"67","author":"Park","year":"2024","journal-title":"Appl. Biol. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Ali, A., Cottrell, J.J., and Dunshea, F.R. (2023). Antioxidant, Alpha-Glucosidase Inhibition Activities, In Silico Molecular Docking and Pharmacokinetics Study of Phenolic Compounds from Native Australian Fruits and Spices. Antioxidants, 12.","DOI":"10.3390\/antiox12020254"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"\u0106orkovi\u0107, I., Ga\u0161o-Soka\u010d, D., Pichler, A., \u0160imunovi\u0107, J., and Kopjar, M. (2022). Dietary Polyphenols as Natural Inhibitors of \u03b1-Amylase and \u03b1-Glucosidase. Life, 12.","DOI":"10.3390\/life12111692"},{"key":"ref_39","first-page":"201","article-title":"\u03b1-Glucosidase Inhibitory Activity of Kaempferol-3-O-Rutinoside","volume":"6","author":"Habtemariam","year":"2011","journal-title":"Nat. Prod. Commun."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"9680508","DOI":"10.1155\/2020\/9680508","article-title":"Use of Chlorogenic Acid against Diabetes Mellitus and Its Complications","volume":"2020","author":"Yan","year":"2020","journal-title":"J. Immunol. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1021\/acsfoodscitech.3c00146","article-title":"Synergistic Effect of Acarbose\u2013Chlorogenic Acid on \u03b1-Glucosidase Inhibition: Kinetics and Interaction Studies Reveal Mixed-Type Inhibition and Denaturant Effect of Chlorogenic Acid","volume":"3","author":"Abioye","year":"2023","journal-title":"ACS Food Sci. Technol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"136102","DOI":"10.1016\/j.foodchem.2023.136102","article-title":"Inhibition Mechanism of \u03b1-Glucosidase Inhibitors Screened from Tartary Buckwheat and Synergistic Effect with Acarbose","volume":"420","author":"Han","year":"2023","journal-title":"Food Chem."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Lee, D., Park, J., Lee, S., and Kang, K. (2021). In Vitro Studies to Assess the \u03b1-Glucosidase Inhibitory Activity and Insulin Secretion Effect of Isorhamnetin 3-O-Glucoside and Quercetin 3-O-Glucoside Isolated from Salicornia Herbacea. Processes, 9.","DOI":"10.3390\/pr9030483"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1002\/ardp.19683010906","article-title":"Zur Kenntnis Der in Rum\u00e4nien Akklimatisierten Pflanze Berberis crataegina DC","volume":"301","author":"Petcu","year":"1968","journal-title":"Arch. Pharm."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Singh, N., and Sharma, B. (2018). Toxicological Effects of Berberine and Sanguinarine. Front. Mol. Biosci., 5.","DOI":"10.3389\/fmolb.2018.00021"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Cha, H.-R., Kim, J.-S., Ryu, J.-H., and Cho, H.-J. (2025). Investigating Neuroprotective Effects of Berberine on Mitochondrial Dysfunction and Autophagy Impairment in Parkinson\u2019s Disease. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26157342"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"41082","DOI":"10.1038\/srep41082","article-title":"Hormetic Effect of Panaxatriol Saponins Confers Neuroprotection in PC12 Cells and Zebrafish through PI3K\/AKT\/MTOR and AMPK\/SIRT1\/FOXO3 Pathways","volume":"7","author":"Zhang","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"174","DOI":"10.2203\/dose-response.07-004.Mattson","article-title":"Viewpoint: Mechanisms of Action and Therapeutic Potential of Neurohormetic Phytochemicals","volume":"5","author":"Mattson","year":"2007","journal-title":"Dose-Response"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e05137","DOI":"10.1016\/j.heliyon.2020.e05137","article-title":"Anti-Diabetic, Diabetic Neuropathy Protective Action and Mechanism of Action Involving Oxidative Pathway of Chlorogenic Acid Isolated from Selinum vaginatum Roots in Rats","volume":"6","author":"Saraswat","year":"2020","journal-title":"Heliyon"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.ejphar.2015.12.021","article-title":"Rutin Ameliorates Diabetic Neuropathy by Lowering Plasma Glucose and Decreasing Oxidative Stress via Nrf2 Signaling Pathway in Rats","volume":"771","author":"Tian","year":"2016","journal-title":"Eur. J. Pharmacol."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Zhang, Q., Song, W., Zhao, B., Xie, J., Sun, Q., Shi, X., Yan, B., Tian, G., and Liang, X. (2021). Quercetin Attenuates Diabetic Peripheral Neuropathy by Correcting Mitochondrial Abnormality via Activation of AMPK\/PGC-1\u03b1 Pathway in Vivo and in Vitro. Front. Neurosci., 15.","DOI":"10.3389\/fnins.2021.636172"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Ho, C.-L., Kao, N.-J., Lin, C.-I., Cross, T.-W.L., and Lin, S.-H. (2022). Quercetin Increases Mitochondrial Biogenesis and Reduces Free Radicals in Neuronal SH-SY5Y Cells. Nutrients, 14.","DOI":"10.3390\/nu14163310"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Lim, C., Zhen, A.X., Ok, S., Fernando, P.D.S.M., Herath, H.M.U.L., Piao, M.J., Kang, K.A., and Hyun, J.W. (2022). Hesperidin Protects SH-SY5Y Neuronal Cells against High Glucose-Induced Apoptosis via Regulation of MAPK Signaling. Antioxidants, 11.","DOI":"10.3390\/antiox11091707"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Ciarlo, L., Marzoli, F., Minosi, P., Matarrese, P., and Pieretti, S. (2021). Ammonium Glycyrrhizinate Prevents Apoptosis and Mitochondrial Dysfunction Induced by High Glucose in SH-SY5Y Cell Line and Counteracts Neuropathic Pain in Streptozotocin-Induced Diabetic Mice. Biomedicines, 9.","DOI":"10.3390\/biomedicines9060608"},{"key":"ref_55","first-page":"456","article-title":"Cytotoxicity Screening and Antioxidant Capacity Assessment of the Inner Perianth Segments of 14 Rumex Species Grown in T\u00fcrkiye","volume":"48","author":"Erkmen","year":"2024","journal-title":"Ank. Univ. Eczaci. Fak. Derg."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Ersoz, B., Erkmen, Y., Aydin, N., Ari, B., Baran, M.Y., Karaoglanoglu, S., and Bakirhan, N.K. (2026). Effects of Chlorogenic Acid and Total Phenolic Content of Coffees on the Color Stability, Surface Roughness, and Microhardness of Resin Composites. BMC Oral Health, 26.","DOI":"10.1186\/s12903-026-07784-y"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Papoti, V.T., Papageorgiou, M., Dervisi, K., Alexopoulos, E., Apostolidis, K., and Petridis, D. (2018). Screening Olive Leaves from Unexploited Traditional Greek Cultivars for Their Phenolic Antioxidant Dynamic. Foods, 7.","DOI":"10.3390\/foods7120197"},{"key":"ref_58","first-page":"252","article-title":"\u201cTotal Flavonoid\u201d Content Assessment via Aluminum [Al(III)] Complexation Reactions: What Do We Really Measure?","volume":"23","author":"Papoti","year":"2011","journal-title":"Ital. J. Food Sci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/S0023-6438(95)80008-5","article-title":"Use of a Free Radical Method to Evaluate Antioxidant Activity","volume":"28","author":"Cuvelier","year":"1995","journal-title":"LWT Food Sci. Technol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.1021\/np100366k","article-title":"Chlorinated Iridoid Glucosides from Veronica Longifolia and Their Antioxidant Activity","volume":"73","author":"Jensen","year":"2010","journal-title":"J. Nat. Prod."},{"key":"ref_61","first-page":"17","article-title":"Antioxidant Activity, Total Phenolic and Flavonoid Contents of Some Tanacetum L. (Asteraceae) Taxa Growing in Turkey","volume":"41","year":"2016","journal-title":"FABAD J. Pharm. Sci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"7970","DOI":"10.1021\/jf048741x","article-title":"Novel Total Antioxidant Capacity Index for Dietary Polyphenols and Vitamins C and E, Using Their Cupric Ion Reducing Capability in the Presence of Neocuproine: CUPRAC Method","volume":"52","author":"Apak","year":"2004","journal-title":"J. Agric. Food Chem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1177\/09731296241277295","article-title":"Phytochemical Profile and Antioxidant, Enzyme-Inhibitory, and Cytotoxic Potential of Endemic Cynoglottis chetikiana subsp. chetikiana","volume":"21","author":"Baran","year":"2025","journal-title":"Pharmacogn. Mag."},{"key":"ref_64","first-page":"267","article-title":"Screening of Fifteen Indian Ayurvedic Plants for Alpha-Glucosidase Inhibitory Activity and Enzyme Kinetics","volume":"3","author":"Bachhawat","year":"2011","journal-title":"Int. J. Pharm. Pharm. Sci."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"5421","DOI":"10.1046\/j.1432-1327.2000.01606.x","article-title":"Investigation of the Alamar Blue (Resazurin) Fluorescent Dye for the Assessment of Mammalian Cell Cytotoxicity","volume":"267","author":"Wilson","year":"2000","journal-title":"Eur. J. Biochem."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2699","DOI":"10.1080\/14786419.2018.1460838","article-title":"Cure of Human Diabetic Neuropathy by HPLC Validated Bark Extract of Onosma echioides L. Root","volume":"33","author":"Shoaib","year":"2019","journal-title":"Nat. Prod. Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.indcrop.2016.06.029","article-title":"Insight into Anticholinesterase and Antioxidant Potential of Thirty-Four Rosaceae Samples and Phenolic Characterization of the Active Extracts by HPLC","volume":"91","author":"Ekin","year":"2016","journal-title":"Ind. Crops Prod."},{"key":"ref_68","unstructured":"International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) (2005). Q2(R1) Validation of Analytical Procedures: Text and Methodology, ICH."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"120692","DOI":"10.1016\/j.jep.2025.120692","article-title":"Non-Targeted Metabolomic Profiling of Cistus Species and Association with Anticholinesterase Efficacy for Alzheimer\u2019s Disease: In vitro and in silico Evaluation","volume":"355","author":"Kahraman","year":"2026","journal-title":"J. Ethnopharmacol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1038\/nmeth.3393","article-title":"MS-DIAL: Data-Independent MS\/MS Deconvolution for Comprehensive Metabolome Analysis","volume":"12","author":"Tsugawa","year":"2015","journal-title":"Nat. Methods"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1038\/nmeth.4512","article-title":"Identifying Metabolites by Integrating Metabolome Databases with Mass Spectrometry Cheminformatics","volume":"15","author":"Lai","year":"2018","journal-title":"Nat. Methods"}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/19\/9\/1365\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T18:35:52Z","timestamp":1787942152000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/19\/9\/1365"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,28]]},"references-count":71,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["ph19091365"],"URL":"https:\/\/doi.org\/10.3390\/ph19091365","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,28]]}}}