{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T21:41:36Z","timestamp":1769722896502,"version":"3.49.0"},"reference-count":40,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,7,29]],"date-time":"2021-07-29T00:00:00Z","timestamp":1627516800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Hubei Provincial Key Research and Development Program","award":["2020BBA050"],"award-info":[{"award-number":["2020BBA050"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Tartary buckwheat is used as an ingredient in flour and tea, as well as in traditional Chinese medicine for its antioxidant effects. Here, we found that an ethanol extract of tartary buckwheat (TBE) potently induced autophagy flux in HeLa cells by suppressing mTORC1 activity, as revealed by dephosphorylation of the mTORC1 substrates Ulk1, S6K, and 4EBP, as well as by the nuclear translocation of transcriptional factor EB. In addition to non-selective bulk autophagy, TBE also induced aggrephagy, which is defined as autophagy against aggregated proteins. Quercetin is a flavonol found at high levels in TBE. We showed that quercetin induced both non-selective bulk autophagy and aggrephagy. These effects were also observed in Huh-7 cells derived from hepatocytes. Thus, aggrephagy induction by TBE and quercetin may relieve alcoholic hepatitis, which is closely linked to the accumulation of protein aggregations called Mallory\u2013Denk bodies.<\/jats:p>","DOI":"10.3390\/antiox10081217","type":"journal-article","created":{"date-parts":[[2021,7,29]],"date-time":"2021-07-29T10:47:46Z","timestamp":1627555666000},"page":"1217","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Quercetin in Tartary Buckwheat Induces Autophagy against Protein Aggregations"],"prefix":"10.3390","volume":"10","author":[{"given":"Sumiko","family":"Ikari","sequence":"first","affiliation":[{"name":"Center for Frontier of Oral Sciences, Graduate School of Dentistry, Osaka University, Osaka 5650871, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiang","family":"Yang","sequence":"additional","affiliation":[{"name":"Hubei Provincial Key Lab for Quality and Safety of Traditional Chinese Medicine Health Food, Daye 435100, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiou-Ling","family":"Lu","sequence":"additional","affiliation":[{"name":"Center for Frontier of Oral Sciences, Graduate School of Dentistry, Osaka University, Osaka 5650871, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuancai","family":"Liu","sequence":"additional","affiliation":[{"name":"Hubei Provincial Key Lab for Quality and Safety of Traditional Chinese Medicine Health Food, Daye 435100, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feike","family":"Hao","sequence":"additional","affiliation":[{"name":"Center for Frontier of Oral Sciences, Graduate School of Dentistry, Osaka University, Osaka 5650871, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guoqiang","family":"Tong","sequence":"additional","affiliation":[{"name":"Jing Brand Company, Ltd., Daye 435100, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiguang","family":"Lu","sequence":"additional","affiliation":[{"name":"Jing Brand Company, Ltd., Daye 435100, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3581-7961","authenticated-orcid":false,"given":"Takeshi","family":"Noda","sequence":"additional","affiliation":[{"name":"Center for Frontier of Oral Sciences, Graduate School of Dentistry, Osaka University, Osaka 5650871, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1146\/annurev-cellbio-092910-154005","article-title":"The Role of Atg Proteins in Autophagosome Formation","volume":"27","author":"Mizushima","year":"2011","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1038\/s41580-020-0241-0","article-title":"Mechanisms Governing Autophagosome Biogenesis","volume":"21","author":"Nakatogawa","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"5425","DOI":"10.1074\/jbc.R117.810739","article-title":"Autophagy and Disease","volume":"293","author":"Thorburn","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/nchembio.500","article-title":"Chemical Modulators of Autophagy as Biological Probes and Potential Therapeutics","volume":"7","author":"Fleming","year":"2011","journal-title":"Nat. Chem. Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1016\/j.jep.2016.10.069","article-title":"Autophagy Modulators from Traditional Chinese Medicine: Mechanisms and Therapeutic Potentials for Cancer and Neurodegenerative Diseases","volume":"194","author":"Wang","year":"2016","journal-title":"J. Ethnopharmacol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Ikari, S., Lu, S.-L., Hao, F., Imai, K., Araki, Y., Yamamoto, Y., Tsai, C.-Y., Nishiyama, Y., Shitan, N., and Yoshimori, T. (2020). Starvation-Induced Autophagy via Calcium-Dependent TFEB Dephosphorylation Is Suppressed by Shigyakusan. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0230156"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4770","DOI":"10.3390\/ijms12084770","article-title":"Anti-Fatigue Properties of Tartary Buckwheat Extracts in Mice","volume":"12","author":"Jin","year":"2011","journal-title":"Int. J. Mol. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2018\/6712407","article-title":"The Effects of Buckwheat Leaf and Flower Extracts on Antioxidant Status in Mouse Organs","volume":"2018","author":"Sadauskiene","year":"2018","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/j.indcrop.2013.04.039","article-title":"Flavonoid Composition, Antibacterial and Antioxidant Properties of Tartary Buckwheat Bran Extract","volume":"49","author":"Wang","year":"2013","journal-title":"Ind. Crop. Prod."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0076-6879(08)03601-X","article-title":"Monitoring Autophagy in Mammalian Cultured Cells through the Dynamics of LC3","volume":"Volume 452","author":"Kimura","year":"2009","journal-title":"Methods in Enzymology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"5720","DOI":"10.1093\/emboj\/19.21.5720","article-title":"LC3, a Mammalian Homologue of Yeast Apg8p, Is Localized in Autophagosome Membranes after Processing","volume":"19","author":"Kabeya","year":"2000","journal-title":"EMBO J."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"452","DOI":"10.4161\/auto.4451","article-title":"Dissection of the Autophagosome Maturation Process by a Novel Reporter Protein, Tandem Fluorescent-Tagged LC3","volume":"3","author":"Kimura","year":"2007","journal-title":"Autophagy"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Noda, T. (2017). Regulation of Autophagy through TORC1 and MTORC1. Biomolecules, 7.","DOI":"10.3390\/biom7030052"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"84","DOI":"10.4161\/auto.1.2.1697","article-title":"Lysosomal Turnover, but Not a Cellular Level, of Endogenous LC3 Is a Marker for Autophagy","volume":"1","author":"Tanida","year":"2005","journal-title":"Autophagy"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1083\/jcb.152.4.657","article-title":"Dissection of Autophagosome Formation Using Apg5-Deficient Mouse Embryonic Stem Cells","volume":"152","author":"Mizushima","year":"2001","journal-title":"J. Cell Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.ceb.2009.12.004","article-title":"The Role of the Atg1\/ULK1 Complex in Autophagy Regulation","volume":"22","author":"Mizushima","year":"2010","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3396","DOI":"10.1016\/j.febslet.2007.06.040","article-title":"Human WIPI-1 Puncta-Formation: A Novel Assay to Assess Mammalian Autophagy","volume":"581","author":"Ruckerbauer","year":"2007","journal-title":"FEBS Lett."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1126\/science.1204592","article-title":"TFEB Links Autophagy to Lysosomal Biogenesis","volume":"332","author":"Settembre","year":"2011","journal-title":"Science"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1038\/ncb2152","article-title":"AMPK and MTOR Regulate Autophagy through Direct Phosphorylation of Ulk1","volume":"13","author":"Kim","year":"2011","journal-title":"Nat. Cell Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1128\/MCB.24.1.200-216.2004","article-title":"MTOR Controls Cell Cycle Progression through Its Cell Growth Effectors S6K1 and 4E-BP1\/Eukaryotic Translation Initiation Factor 4E","volume":"24","author":"Fingar","year":"2004","journal-title":"MCB"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1714","DOI":"10.1016\/j.jmb.2016.02.004","article-title":"Mechanisms of Selective Autophagy","volume":"428","author":"Zaffagnini","year":"2016","journal-title":"J. Mol. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/j.molcel.2009.01.020","article-title":"A Role for NBR1 in Autophagosomal Degradation of Ubiquitinated Substrates","volume":"33","author":"Kirkin","year":"2009","journal-title":"Mol. Cell"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1016\/j.cell.2007.10.035","article-title":"Homeostatic Levels of P62 Control Cytoplasmic Inclusion Body Formation in Autophagy-Deficient Mice","volume":"131","author":"Komatsu","year":"2007","journal-title":"Cell"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"994","DOI":"10.3136\/nskkk1962.39.994","article-title":"An Enzyme Degrading Rutin in Tartary Buckwheat Seeds","volume":"39","author":"Yasuda","year":"1992","journal-title":"Nippon Shokuhin Kogyo Gakkaishi"},{"key":"ref_25","first-page":"796","article-title":"Purification, characterization and partial primary structure analysis of rutin-degrading enzyme in tartary buckwheat seeds","volume":"33","author":"Zhang","year":"2017","journal-title":"Sheng Wu Gong Cheng Xue Bao"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"French, S., Masouminia, M., Samadzadeh, S., Tillman, B., Mendoza, A., and French, B. (2017). Role of Protein Quality Control Failure in Alcoholic Hepatitis Pathogenesis. Biomolecules, 7.","DOI":"10.3390\/biom7010011"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1083\/jcb.200412022","article-title":"Impairment of Starvation-Induced and Constitutive Autophagy in Atg7-Deficient Mice","volume":"169","author":"Komatsu","year":"2005","journal-title":"J. Cell Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"966","DOI":"10.4161\/auto.7.9.15863","article-title":"Quercetin Induces Protective Autophagy in Gastric Cancer Cells: Involvement of Akt-MTOR- and Hypoxia-Induced Factor 1\u03b1-Mediated Signaling","volume":"7","author":"Wang","year":"2011","journal-title":"Autophagy"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1007\/s00418-011-0869-0","article-title":"Proteasome Inhibition by Quercetin Triggers Macroautophagy and Blocks MTOR Activity","volume":"137","author":"Klappan","year":"2012","journal-title":"Histochem. Cell Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.phrs.2015.06.006","article-title":"Quercetin Inhibits the MTORC1\/P70S6K Signaling-Mediated Renal Tubular Epithelial\u2013Mesenchymal Transition and Renal Fibrosis in Diabetic Nephropathy","volume":"99","author":"Lu","year":"2015","journal-title":"Pharmacol. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1038\/s41419-020-03183-5","article-title":"Quercetin Promotes in Vitro Maturation of Oocytes from Humans and Aged Mice","volume":"11","author":"Cao","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"613006","DOI":"10.3389\/fcell.2020.613006","article-title":"Quercetin Suppresses Apoptosis and Attenuates Intervertebral Disc Degeneration via the SIRT1-Autophagy Pathway","volume":"8","author":"Wang","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1002\/tox.23020","article-title":"Quercetin Induces Autophagy in Myelodysplastic Bone Marrow Including Hematopoietic Stem\/Progenitor Compartment","volume":"36","author":"Daw","year":"2021","journal-title":"Environ. Toxicol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1080\/15569527.2020.1860082","article-title":"Quercetin Protects Retina External Barrier from Oxidative Stress Injury by Promoting Autophagy","volume":"40","author":"Li","year":"2021","journal-title":"Cutan. Ocul. Toxicol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1080\/01616412.2016.1240393","article-title":"Quercetin Attenuates Neuronal Autophagy and Apoptosis in Rat Traumatic Brain Injury Model via Activation of PI3K\/Akt Signaling Pathway","volume":"38","author":"Du","year":"2016","journal-title":"Neurol. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/15548627.2020.1797280","article-title":"Guidelines for the Use and Interpretation of Assays for Monitoring Autophagy (4th Edition)","volume":"17","author":"Klionsky","year":"2021","journal-title":"Autophagy"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2018\/5073420","article-title":"Enhancing TFEB-Mediated Cellular Degradation Pathways by the MTORC1 Inhibitor Quercetin","volume":"2018","author":"Huang","year":"2018","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1101\/gad.2016211","article-title":"Autophagy-Deficient Mice Develop Multiple Liver Tumors","volume":"25","author":"Takamura","year":"2011","journal-title":"Genes Dev."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Yu, X., Xu, Y., Zhang, S., Sun, J., Liu, P., Xiao, L., Tang, Y., Liu, L., and Yao, P. (2016). Quercetin Attenuates Chronic Ethanol-Induced Hepatic Mitochondrial Damage through Enhanced Mitophagy. Nutrients, 8.","DOI":"10.3390\/nu8010027"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.fct.2018.12.028","article-title":"Quercetin Alleviates Ethanol-Induced Liver Steatosis Associated with Improvement of Lipophagy","volume":"125","author":"Zeng","year":"2019","journal-title":"Food Chem. Toxicol."}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/10\/8\/1217\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:36:34Z","timestamp":1760164594000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/10\/8\/1217"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,29]]},"references-count":40,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2021,8]]}},"alternative-id":["antiox10081217"],"URL":"https:\/\/doi.org\/10.3390\/antiox10081217","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,29]]}}}