{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T15:23:33Z","timestamp":1792164213305,"version":"4.4.0"},"reference-count":56,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,5,8]],"date-time":"2024-05-08T00:00:00Z","timestamp":1715126400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Mahidol University"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>A previous study reported that the ethanolic extract of the edible fern, Diplazium esculentum (Retz.) Sw. (DE), obtained from a non-optimized extraction condition exhibited anti-Alzheimer\u2019s disease (AD) properties through the inhibition of a rate-limiting enzyme in amyloid peptide formation, \u03b2-secretase-1 (BACE-1). Nevertheless, a non-optimized or suboptimal extraction may lead to several issues, such as a reduction in extraction efficiency and increased time and plant materials. In this study, extraction of the DE was optimized to obtain appropriate BACE-1 inhibition using a Box\u2013Behnken design (BBD) and response surface methodology (RSM). Data revealed that the optimal extraction condition was 70% (v\/v) aqueous ethanol, 50 min extraction time, 30 \u00b0C extraction temperature, and 1:30 g\/mL solid\/liquid ratio, giving BACE-1 inhibition at 56.33%. In addition, the extract also exhibited significant antioxidant activities compared to the non-optimized extraction. Metabolomic phytochemical profiles and targeted phytochemical analyses showed that kaempferol, quercetin, and their derivatives as well as rosmarinic acid were abundant in the extract. The optimized DE extract also acted synergistically with donepezil, an AD drug suppressing BACE-1 activities. Data received from Drosophila-expressing human amyloid precursor proteins (APPs) and BACE-1, representing the amyloid hypothesis, showed that the optimized DE extract penetrated the fly brains, suppressed BACE-1 activities, and improved locomotor functions. The extract quenched the expression of glutathione S transferase D1 (GSTD1), inositol-requiring enzyme (IRE-1), and molecular chaperone-binding immunoglobulin (Bip), while donepezil suppressed these genes and other genes involved in antioxidant and endoplasmic reticulum (ER) stress response, including superoxide dismutase type 1 (SOD1), activating transcription factor 6 (ATF-6), and protein kinase R-like endoplasmic reticulum kinase (PERK). To sum up, the optimized extraction condition reduced extraction time while resulting in higher phytochemicals, antioxidants, and BACE-1 inhibitors.<\/jats:p>","DOI":"10.3390\/molecules29102204","type":"journal-article","created":{"date-parts":[[2024,5,8]],"date-time":"2024-05-08T09:58:56Z","timestamp":1715162336000},"page":"2204","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Box\u2013Behnken Design-Based Optimization of Phytochemical Extraction from Diplazium esculentum (Retz.) Sw. Associated with Its Antioxidant and Anti-Alzheimer\u2019s Properties"],"prefix":"10.3390","volume":"29","author":[{"given":"Sirawit","family":"Kongsung","sequence":"first","affiliation":[{"name":"Master of Science Program in Toxicology and Nutrition for Food Safety, Institute of Nutrition, Mahidol University, Salaya, Phuttamonthon, Nakhon Pathom 73170, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4282-4908","authenticated-orcid":false,"given":"Woorawee","family":"Inthachat","sequence":"additional","affiliation":[{"name":"Institute of Nutrition, Mahidol University, Salaya, Phuttamonthon, Nakhon Pathom 73170, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boonrat","family":"Chantong","sequence":"additional","affiliation":[{"name":"Department of Pre-Clinical and Applied Animal Science, Faculty of Veterinary Science, Mahidol University, Salaya, Phuttamonthon, Nakhon Pathom 73170, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5887-6329","authenticated-orcid":false,"given":"Uthaiwan","family":"Suttisansanee","sequence":"additional","affiliation":[{"name":"Institute of Nutrition, Mahidol University, Salaya, Phuttamonthon, Nakhon Pathom 73170, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1240-3531","authenticated-orcid":false,"given":"Nattira","family":"On-Nom","sequence":"additional","affiliation":[{"name":"Institute of Nutrition, Mahidol University, Salaya, Phuttamonthon, Nakhon Pathom 73170, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1093-1621","authenticated-orcid":false,"given":"Chaowanee","family":"Chupeerach","sequence":"additional","affiliation":[{"name":"Institute of Nutrition, Mahidol University, Salaya, Phuttamonthon, Nakhon Pathom 73170, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6644-6396","authenticated-orcid":false,"given":"Sirinapa","family":"Thangsiri","sequence":"additional","affiliation":[{"name":"Institute of Nutrition, Mahidol University, Salaya, Phuttamonthon, Nakhon Pathom 73170, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6219-386X","authenticated-orcid":false,"given":"Pornsiri","family":"Pitchakarn","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7590-7024","authenticated-orcid":false,"given":"Piya","family":"Temviriyanukul","sequence":"additional","affiliation":[{"name":"Institute of Nutrition, Mahidol University, Salaya, Phuttamonthon, Nakhon Pathom 73170, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Alzheimer\u2019s Association (2023). 2023 Alzheimer\u2019s disease facts and figures. Alzheimers Dement., 19, 1598\u20131695.","DOI":"10.1002\/alz.13016"},{"key":"ref_2","unstructured":"Huang, X. (2020). Alzheimer\u2019s Disease: Drug Discovery, Exon Publications."},{"key":"ref_3","unstructured":"WHO (2019). Risk Reduction of Cognitive Decline and Dementia: WHO Guidelines, WHO."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s40035-018-0107-y","article-title":"Alzheimer\u2019s disease hypothesis and related therapies","volume":"7","author":"Du","year":"2018","journal-title":"Transl. Neurodegener."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/S0166-2236(00)01749-5","article-title":"Targeting small A\u03b2 oligomers: The solution to an Alzheimer\u2019s disease conundrum?","volume":"24","author":"Klein","year":"2001","journal-title":"Trends Neurosci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"117996","DOI":"10.1016\/j.lfs.2020.117996","article-title":"Alzheimer\u2019s disease; a review of the pathophysiological basis and therapeutic interventions","volume":"256","author":"Abeysinghe","year":"2020","journal-title":"Life Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.molmed.2007.12.002","article-title":"Amyloid beta, mitochondrial dysfunction and synaptic damage: Implications for cognitive decline in aging and Alzheimer\u2019s disease","volume":"14","author":"Reddy","year":"2008","journal-title":"Trends Mol. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1038\/374647a0","article-title":"Activation of microglial cells by \u03b2-amyloid protein and interferon-\u03b3","volume":"374","author":"Meda","year":"1995","journal-title":"Nature"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1523\/JNEUROSCI.21-04-01179.2001","article-title":"\u03b2-Amyloid stimulation of microglia and monocytes results in TNF\u03b1-dependent expression of inducible nitric oxide synthase and neuronal apoptosis","volume":"21","author":"Combs","year":"2001","journal-title":"J. Neurosci."},{"key":"ref_10","first-page":"197","article-title":"Two Randomized Phase 3 Studies of Aducanumab in Early Alzheimer\u2019s Disease","volume":"9","author":"Aisen","year":"2022","journal-title":"J. Prev. Alzheimers Dis."},{"key":"ref_11","unstructured":"(2024, March 01). National Institute on Aging: How Is Alzheimer\u2019s Disease Treated?, Available online: https:\/\/www.nia.nih.gov\/health\/alzheimers-treatment\/how-alzheimers-disease-treated."},{"key":"ref_12","unstructured":"Manickam, V., and Irudayaraj, V. (2003). Pteridophyte Flora of Nilgiris, South India, Bishen Singh Mahendra Pal Singh."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Zannah, F., Amin, M., Suwono, H., and Lukiati, B. (2017, January 16\u201321). Phytochemical screening of Diplazium esculentum as medicinal plant from Central Kalimantan, Indonesia. Proceedings of the AIP Conference Proceedings, Provo, UT, USA.","DOI":"10.1063\/1.4983439"},{"key":"ref_14","first-page":"1251","article-title":"Preliminary studies on anti-inflammatory activities of Diplazium esculentum in experimental animal models","volume":"2","author":"Kaushik","year":"2011","journal-title":"Int. J. Pharm. Sci. Res."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Kala, C.P. (2005). Ethnomedicinal botany of the Apatani in the Eastern Himalayan region of India. J. Ethnobiol. Ethnomed., 1.","DOI":"10.1186\/1746-4269-1-11"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"23796","DOI":"10.1038\/s41598-021-03142-w","article-title":"Diplazium esculentum (Retz.) Sw. reduces BACE-1 activities and amyloid peptides accumulation in Drosophila models of Alzheimer\u2019s disease","volume":"11","author":"Kunkeaw","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Green, K.D., Fosso, M.Y., and Garneau-Tsodikova, S. (2018). Multifunctional Donepezil Analogues as Cholinesterase and BACE1 Inhibitors. Molecules, 23.","DOI":"10.3390\/molecules23123252"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Inthachat, W., Chantong, B., Pitchakarn, P., Takoon, C., Karinchai, J., Suttisansanee, U., and Temviriyanukul, P. (2024). Enhancing Therapeutic Efficacy of Donepezil, an Alzheimer\u2019s Disease Drug, by Diplazium esculentum (Retz.) Sw. and Its Phytochemicals. Pharmaceuticals, 17.","DOI":"10.3390\/ph17030341"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1016\/j.talanta.2008.05.019","article-title":"Response surface methodology (RSM) as a tool for optimization in analytical chemistry","volume":"76","author":"Bezerra","year":"2008","journal-title":"Talanta"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Ahmad, A., Rehman, M.U., Wali, A.F., El-Serehy, H.A., Al-Misned, F.A., Maodaa, S.N., Aljawdah, H.M., Mir, T.M., and Ahmad, P. (2020). Box-Behnken Response Surface Design of Polysaccharide Extraction from Rhododendron arboreum and the Evaluation of Its Antioxidant Potential. Molecules, 25.","DOI":"10.3390\/molecules25173835"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Al Ubeed, H.M.S., Bhuyan, D.J., Alsherbiny, M.A., Basu, A., and Vuong, Q.V. (2022). A Comprehensive Review on the Techniques for Extraction of Bioactive Compounds from Medicinal Cannabis. Molecules, 27.","DOI":"10.3390\/molecules27030604"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1744","DOI":"10.1002\/1097-0010(20000915)80:12<1744::AID-JSFA725>3.0.CO;2-W","article-title":"Phytochemicals: Nutraceuticals and human health","volume":"80","author":"Dillard","year":"2000","journal-title":"J. Sci. Food Agric."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"823","DOI":"10.3233\/JAD-130836","article-title":"The selective BACE1 inhibitor VIa reduces amyloid-\u03b2 production in cell and mouse models of Alzheimer\u2019s disease","volume":"37","author":"Cheng","year":"2013","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"14643","DOI":"10.1073\/pnas.1416637111","article-title":"Structure of nicastrin unveils secrets of \u03b3-secretase","volume":"111","author":"Bolduc","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_25","first-page":"383796","article-title":"The Alzheimer\u2019s amyloid-degrading peptidase, neprilysin: Can we control it?","volume":"2012","author":"Nalivaeva","year":"2012","journal-title":"Int. J. Alzheimer\u2019s Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1021\/acschemneuro.0c00011","article-title":"Molecular Mechanism of Apoptosis by Amyloid \u03b2-Protein Fibrils Formed on Neuronal Cells","volume":"11","author":"Takada","year":"2020","journal-title":"ACS Chem. Neurosci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/1742-2094-6-41","article-title":"ER stress in Alzheimer\u2019s disease: A novel neuronal trigger for inflammation and Alzheimer\u2019s pathology","volume":"6","author":"Salminen","year":"2009","journal-title":"J. Neuroinflamm."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"102294","DOI":"10.1016\/j.ctim.2019.102294","article-title":"Oxidative stress in alzheimer\u2019s disease: A review on emergent natural polyphenolic therapeutics","volume":"49","author":"Cassidy","year":"2020","journal-title":"Complement. Ther. Med."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Huang, W., Gong, Y., and Yan, L. (2023). ER Stress, the Unfolded Protein Response and Osteoclastogenesis: A Review. Biomolecules, 13.","DOI":"10.3390\/biom13071050"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1007\/s12161-010-9139-3","article-title":"Antioxidant activity of pink-flesh guava (Psidium guajava L.): Effect of extraction techniques and solvents","volume":"4","author":"Musa","year":"2011","journal-title":"Food Anal. Methods"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1186\/s13065-017-0324-y","article-title":"Optimization of phenolics and flavonoids extraction conditions of Curcuma Zedoaria leaves using response surface methodology","volume":"11","author":"Azahar","year":"2017","journal-title":"Chem. Cent. J."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1016\/j.jiec.2021.03.031","article-title":"Optimization of phenolics and flavonoids extraction from the fruit of Empetrum nigrum var. japonicum from Jeju Island in South Korea","volume":"98","author":"Zhang","year":"2021","journal-title":"J. Ind. Eng. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.trac.2019.05.037","article-title":"Green extraction of natural products. Origins, current status, and future challenges","volume":"118","author":"Chemat","year":"2019","journal-title":"TrAC Trends Anal. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1016\/j.bjp.2017.03.004","article-title":"Qualitative and quantitative analysis of the phenolic content of Connarus var. angustifolius, Cecropia obtusa, Cecropia palmata and Mansoa alliacea based on HPLC-DAD and UHPLC-ESI-MS\/MS","volume":"27","author":"Pires","year":"2017","journal-title":"Rev. Bras. Farmacogn."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1039\/b000080i","article-title":"Sample preparation in the determination of phenolic compounds in fruits","volume":"125","author":"Antolovich","year":"2000","journal-title":"Analyst"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1917890","DOI":"10.1155\/2021\/1917890","article-title":"Diplazium esculentum (Retz.) Sw.: Ethnomedicinal, Phytochemical, and Pharmacological Overview of the Himalayan Ferns","volume":"2021","author":"Semwal","year":"2021","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Watanabe, M., Miyashita, T., and Devkota, H.P. (2021). Phenolic compounds and ecdysteroids of Diplazium esculentum (Retz.) Sw. (Athyriaceae) from Japan and their chemotaxonomic significance. Biochem. Syst. Ecol., 94.","DOI":"10.1016\/j.bse.2020.104211"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1016\/0031-9422(81)85203-X","article-title":"A flavanone glycoside from Diplazium esculentum","volume":"20","author":"Srivastava","year":"1981","journal-title":"Phytochemistry"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"117818","DOI":"10.1016\/j.jep.2024.117818","article-title":"The traditional utilization, biological activity and chemical composition of edible fern species","volume":"324","author":"Dvorakova","year":"2024","journal-title":"J. Ethnopharmacol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2115","DOI":"10.3390\/nu6052115","article-title":"Antioxidant activity in extracts of 27 indigenous Taiwanese vegetables","volume":"6","author":"Chao","year":"2014","journal-title":"Nutrients"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3717328","DOI":"10.1155\/2018\/3717328","article-title":"Combined Donepezil and Ethanolic Extract of Propolis Improved Memory Better Than Donepezil and Propolis Monotherapy in Wild Type Drosophila melanogaster","volume":"2018","author":"Ayikobua","year":"2018","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2511","DOI":"10.1007\/s11011-021-00749-w","article-title":"Combination of donepezil and gallic acid improves antioxidant status and cholinesterases activity in aluminum chloride-induced neurotoxicity in Wistar rats","volume":"36","author":"Obafemi","year":"2021","journal-title":"Metab. Brain Dis."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1016\/j.bbagen.2008.01.017","article-title":"Flavonols and flavones as BACE-1 inhibitors: Structure-activity relationship in cell-free, cell-based and in silico studies reveal novel pharmacophore features","volume":"1780","author":"Shimmyo","year":"2008","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"562","DOI":"10.6026\/97320630010562","article-title":"Molecular docking of fisetin with AD associated AChE, ABAD and BACE1 proteins","volume":"10","author":"Dash","year":"2014","journal-title":"Bioinformation"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1007\/s12272-001-1139-9","article-title":"Beta-secretase (BACE1) inhibitors from Perilla frutescens var. acuta","volume":"31","author":"Choi","year":"2008","journal-title":"Arch. Pharm. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"98","DOI":"10.3389\/fnagi.2013.00098","article-title":"Neprilysin and A\u03b2 Clearance: Impact of the APP Intracellular Domain in NEP Regulation and Implications in Alzheimer\u2019s Disease","volume":"5","author":"Grimm","year":"2013","journal-title":"Front. Aging Neurosci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2944","DOI":"10.1021\/acschemneuro.3c00486","article-title":"Oxidative Stress Occurs Prior to Amyloid A\u03b2 Plaque Formation and Tau Phosphorylation in Alzheimer\u2019s Disease: Role of Glutathione and Metal Ions","volume":"14","author":"Roy","year":"2023","journal-title":"ACS Chem. Neurosci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1007\/s00401-005-1038-0","article-title":"The unfolded protein response is activated in Alzheimer\u2019s disease","volume":"110","author":"Hoozemans","year":"2005","journal-title":"Acta Neuropathol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1007\/s00401-017-1694-x","article-title":"IRE1 signaling exacerbates Alzheimer\u2019s disease pathogenesis","volume":"134","author":"Cornejo","year":"2017","journal-title":"Acta Neuropathol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1038\/s41419-022-05153-5","article-title":"ER stress and UPR in Alzheimer\u2019s disease: Mechanisms, pathogenesis, treatments","volume":"13","author":"Ajoolabady","year":"2022","journal-title":"Cell Death Dis."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Sirichai, P., Kittibunchakul, S., Thangsiri, S., On-Nom, N., Chupeerach, C., Temviriyanukul, P., Inthachat, W., Nuchuchua, O., Aursalung, A., and Sahasakul, Y. (2022). Impact of Drying Processes on Phenolics and In Vitro Health-Related Activities of Indigenous Plants in Thailand. Plants, 11.","DOI":"10.3390\/plants11030294"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Inthachat, W., Temviriyanukul, P., On-Nom, N., Kanoongon, P., Thangsiri, S., Chupeerach, C., and Suttisansanee, U. (2023). Optimization of Phytochemical-Rich Citrus maxima Albedo Extract Using Response Surface Methodology. Molecules, 28.","DOI":"10.3390\/molecules28104121"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"101","DOI":"10.4103\/0974-8490.197797","article-title":"Synergisms in Alpha-glucosidase Inhibition and Antioxidant Activity of Camellia sinensis L. Kuntze and Eugenia uniflora L. Ethanolic Extracts","volume":"9","author":"Vinholes","year":"2017","journal-title":"Pharmacogn. Res"},{"key":"ref_54","first-page":"1934578X1501001110","article-title":"Combination of antioxidants from different sources could offer synergistic benefits: A case study of tea and ginger blend","volume":"10","author":"Makanjuola","year":"2015","journal-title":"Nat. Prod. Commun."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3038","DOI":"10.1016\/j.bbadis.2018.06.017","article-title":"Depletion of Ubiquilin induces an augmentation in soluble ubiquitinated Drosophila TDP-43 to drive neurotoxicity in the fly","volume":"1864","author":"Jantrapirom","year":"2018","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1354393","DOI":"10.3389\/fsufs.2024.1354393","article-title":"Antioxidant and antimicrobial activities of mango peel and radish peel-a comparative investigation","volume":"8","author":"Koirala","year":"2024","journal-title":"Front. Sustain. Food Syst."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/29\/10\/2204\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:42:04Z","timestamp":1760107324000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/29\/10\/2204"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,8]]},"references-count":56,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2024,5]]}},"alternative-id":["molecules29102204"],"URL":"https:\/\/doi.org\/10.3390\/molecules29102204","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,8]]}}}