{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T13:35:15Z","timestamp":1786368915741,"version":"build-2736575974"},"reference-count":46,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T00:00:00Z","timestamp":1780099200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"vor","delay-in-days":72,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Parkinson\u2019s disease (PD) is a progressive neurodegenerative disorder lacking disease-modifying therapies. Rotenone (Rot) is widely used to model PD, but its neurotoxicity is not fully understood beyond mitochondrial complex I inhibition. Here, we identify a glycolytic mechanism that contributes to Rot-induced neuronal damage downstream of complex I inhibition. Our in vitro data demonstrate that Rot enhances glycolytic flux, leading to accumulation of methylglyoxal-derived hydroimidazolones (MG-Hs), which drive irreversible cellular damage. Shikonin effectively attenuates Rot-induced apoptosis by inhibiting PKM2, thereby suppressing glycolysis and reducing MG-Hs formation. In a rat model, shikonin robustly improves motor function and preserves nigrostriatal dopaminergic neurons. Collectively, our findings reveal a previously unrecognized glycolytic-mediated pathway involving PKM2-driven glycolysis and MG-Hs accumulation that contributes to rotenone neurotoxicity alongside mitochondrial dysfunction, and highlight shikonin as a promising neuroprotective agent for Parkinson\u2019s disease intervention.<\/jats:p>","DOI":"10.1038\/s41598-026-54865-7","type":"journal-article","created":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T03:45:43Z","timestamp":1780112743000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["PKM2-driven glycolysis mediates rotenone neurotoxicity via MG-Hs in Parkinson\u2019s disease"],"prefix":"10.1038","volume":"16","author":[{"given":"Rong","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia Wen","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Mu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lang","family":"Qu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,30]]},"reference":[{"key":"54865_CR1","doi-asserted-by":"publisher","first-page":"177523","DOI":"10.1016\/j.ejphar.2025.177523","volume":"998","author":"D Soni","year":"2025","unstructured":"Soni, D. et al. Auranofin-loaded chitosan-lipid hybrid nanoparticle protects against rotenone model of Parkinson\u2019s disease via modulation of GSK-3beta\/ Nrf2\/HO-1 signaling. Eur. J. Pharmacol. 998, 177523. https:\/\/doi.org\/10.1016\/j.ejphar.2025.177523 (2025).","journal-title":"Eur. J. Pharmacol."},{"key":"54865_CR2","doi-asserted-by":"publisher","first-page":"e70413","DOI":"10.1002\/jbt.70413","volume":"39","author":"S Upadhayay","year":"2025","unstructured":"Upadhayay, S., Soni, D., Puneet, K., Raloxifene & Antioxidant, F. E. Anti-Inflammatory, and Antiapoptotic Action Against Haloperidol-Induced Tardive Dyskinesia in Rats via Activation of the GPER1\/PI3k\/Akt\/Nrf2\/HO-1 Signaling Pathways. J. Biochem. Mol. Toxicol. 39, e70413. https:\/\/doi.org\/10.1002\/jbt.70413 (2025).","journal-title":"J. Biochem. Mol. Toxicol."},{"key":"54865_CR3","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1007\/s11064-024-04319-1","volume":"50","author":"M Aqeel","year":"2025","unstructured":"Aqeel, M. et al. Glycyrrhizic Acid Mitigates Haloperidol-Induced Neurotoxicity in SHSY-5Y Cells and Rats Via Activation of PI3k\/Akt\/Nrf2 Pathways. Neurochem Res. 50, 75. https:\/\/doi.org\/10.1007\/s11064-024-04319-1 (2025).","journal-title":"Neurochem Res."},{"key":"54865_CR4","doi-asserted-by":"publisher","first-page":"2921","DOI":"10.1007\/s10787-024-01510-2","volume":"32","author":"D Soni","year":"2024","unstructured":"Soni, D., Upadhayay, S., Dhureja, M., Arthur, R. & Kumar, P. Crosstalk between gut-brain axis: unveiling the mysteries of gut ROS in progression of Parkinson\u2019s disease. Inflammopharmacology 32, 2921\u20132941. https:\/\/doi.org\/10.1007\/s10787-024-01510-2 (2024).","journal-title":"Inflammopharmacology"},{"key":"54865_CR5","doi-asserted-by":"publisher","first-page":"866","DOI":"10.1289\/ehp.1002839","volume":"119","author":"CM Tanner","year":"2011","unstructured":"Tanner, C. M. et al. Rotenone, paraquat, and Parkinson\u2019s disease. Environ. Health Perspect. 119, 866\u2013872. https:\/\/doi.org\/10.1289\/ehp.1002839 (2011).","journal-title":"Environ. Health Perspect."},{"key":"54865_CR6","doi-asserted-by":"publisher","first-page":"101164","DOI":"10.1016\/j.redox.2019.101164","volume":"24","author":"V Tapias","year":"2019","unstructured":"Tapias, V., McCoy, J. L. & Greenamyre, J. T. Phenothiazine normalizes the NADH\/NAD(+) ratio, maintains mitochondrial integrity and protects the nigrostriatal dopamine system in a chronic rotenone model of Parkinson\u2019s disease. Redox Biol. 24, 101164. https:\/\/doi.org\/10.1016\/j.redox.2019.101164 (2019).","journal-title":"Redox Biol."},{"key":"54865_CR7","unstructured":"Konnova, E. A. & Swanberg, M. Animal Models of Parkinson\u2019s Disease. In: (eds Stoker, T. B. & Greenland, J. C.) Parkinson\u2019s Disease: Pathogenesis and Clinical Aspects: Brisbane (AU), (2018)."},{"key":"54865_CR8","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1038\/nrneurol.2015.197","volume":"11","author":"L Klingelhoefer","year":"2015","unstructured":"Klingelhoefer, L. & Reichmann, H. Pathogenesis of Parkinson disease\u2013the gut-brain axis and environmental factors. Nat. Rev. Neurol. 11, 625\u2013636. https:\/\/doi.org\/10.1038\/nrneurol.2015.197 (2015).","journal-title":"Nat. Rev. Neurol."},{"key":"54865_CR9","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1016\/j.freeradbiomed.2013.01.003","volume":"62","author":"LH Sanders","year":"2013","unstructured":"Sanders, L. H. & Greenamyre, T. Oxidative damage to macromolecules in human Parkinson disease and the rotenone model. Free Radic Biol. Med. 62, 111\u2013120. https:\/\/doi.org\/10.1016\/j.freeradbiomed.2013.01.003 (2013).","journal-title":"Free Radic Biol. Med."},{"key":"54865_CR10","doi-asserted-by":"publisher","first-page":"110","DOI":"10.3389\/fcell.2017.00110","volume":"5","author":"N Plotegher","year":"2017","unstructured":"Plotegher, N. & Duchen, M. R. Crosstalk between Lysosomes and Mitochondria in Parkinson\u2019s Disease. Front. Cell. Dev. Biol. 5, 110. https:\/\/doi.org\/10.3389\/fcell.2017.00110 (2017).","journal-title":"Front. Cell. Dev. Biol."},{"key":"54865_CR11","doi-asserted-by":"publisher","first-page":"15136","DOI":"10.1073\/pnas.0807581105","volume":"105","author":"WS Choi","year":"2008","unstructured":"Choi, W. S., Kruse, S. E., Palmiter, R. D. & Xia, Z. Mitochondrial complex I inhibition is not required for dopaminergic neuron death induced by rotenone, MPP+, or paraquat. Proc. Natl. Acad. Sci. U S A. 105, 15136\u201315141. https:\/\/doi.org\/10.1073\/pnas.0807581105 (2008).","journal-title":"Proc. Natl. Acad. Sci. U S A"},{"key":"54865_CR12","doi-asserted-by":"publisher","first-page":"855","DOI":"10.3389\/fimmu.2019.00855","volume":"10","author":"S Wetzels","year":"2019","unstructured":"Wetzels, S. et al. Methylglyoxal-Derived Advanced Glycation Endproducts Accumulate in Multiple Sclerosis Lesions. Front. Immunol. 10, 855. https:\/\/doi.org\/10.3389\/fimmu.2019.00855 (2019).","journal-title":"Front. Immunol."},{"key":"54865_CR13","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/j.semcancer.2017.05.006","volume":"49","author":"N Rabbani","year":"2018","unstructured":"Rabbani, N., Xue, M., Weickert, M. O. & Thornalley, P. J. Multiple roles of glyoxalase 1-mediated suppression of methylglyoxal glycation in cancer biology-Involvement in tumour suppression, tumour growth, multidrug resistance and target for chemotherapy. Semin Cancer Biol. 49, 83\u201393. https:\/\/doi.org\/10.1016\/j.semcancer.2017.05.006 (2018).","journal-title":"Semin Cancer Biol."},{"key":"54865_CR14","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1038\/s41398-021-01392-w","volume":"11","author":"T Hara","year":"2021","unstructured":"Hara, T. et al. Glyoxalase I disruption and external carbonyl stress impair mitochondrial function in human induced pluripotent stem cells and derived neurons. Transl Psychiatry. 11, 275. https:\/\/doi.org\/10.1038\/s41398-021-01392-w (2021).","journal-title":"Transl Psychiatry"},{"key":"54865_CR15","doi-asserted-by":"publisher","unstructured":"Wiatrak, B., Kubis-Kubiak, A., Piwowar, A. & Barg, E. PC12 cell line: Cell types, coating of culture vessels, differentiation and other culture conditions. Cells 9. https:\/\/doi.org\/10.3390\/cells9040958 (2020).","DOI":"10.3390\/cells9040958"},{"key":"54865_CR16","doi-asserted-by":"publisher","first-page":"112","DOI":"10.4103\/1673-5374.224380","volume":"13","author":"SJ Wang","year":"2018","unstructured":"Wang, S. J. et al. Effect of moxibustion on mTOR-mediated autophagy in rotenone-induced Parkinson\u2019s disease model rats. Neural Regen Res. 13, 112\u2013118. https:\/\/doi.org\/10.4103\/1673-5374.224380 (2018).","journal-title":"Neural Regen Res."},{"key":"54865_CR17","doi-asserted-by":"publisher","first-page":"931","DOI":"10.1038\/s41591-018-0051-5","volume":"24","author":"SP Yun","year":"2018","unstructured":"Yun, S. P. et al. Block of A1 astrocyte conversion by microglia is neuroprotective in models of Parkinson\u2019s disease. Nat. Med. 24, 931\u2013938. https:\/\/doi.org\/10.1038\/s41591-018-0051-5 (2018).","journal-title":"Nat. Med."},{"key":"54865_CR18","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1016\/j.nbd.2009.01.016","volume":"34","author":"JR Cannon","year":"2009","unstructured":"Cannon, J. R. et al. A highly reproducible rotenone model of Parkinson\u2019s disease. Neurobiol. Dis. 34, 279\u2013290. https:\/\/doi.org\/10.1016\/j.nbd.2009.01.016 (2009).","journal-title":"Neurobiol. Dis."},{"key":"54865_CR19","doi-asserted-by":"publisher","first-page":"1547","DOI":"10.1002\/mds.27077","volume":"32","author":"T Chotibut","year":"2017","unstructured":"Chotibut, T. et al. Ceftriaxone reduces L-dopa-induced dyskinesia severity in 6-hydroxydopamine parkinson\u2019s disease model. Mov. Disord. 32, 1547\u20131556. https:\/\/doi.org\/10.1002\/mds.27077 (2017).","journal-title":"Mov. Disord"},{"key":"54865_CR20","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1111\/j.1755-5949.2012.00337.x","volume":"18","author":"R Kimura","year":"2012","unstructured":"Kimura, R. et al. Acute exposure to the mitochondrial complex I toxin rotenone impairs synaptic long-term potentiation in rat hippocampal slices. CNS Neurosci. Ther. 18, 641\u2013646. https:\/\/doi.org\/10.1111\/j.1755-5949.2012.00337.x (2012).","journal-title":"CNS Neurosci. Ther."},{"key":"54865_CR21","doi-asserted-by":"publisher","first-page":"1316","DOI":"10.1111\/jcmm.13432","volume":"22","author":"WL Hou","year":"2018","unstructured":"Hou, W. L. et al. Inhibition of mitochondrial complex I improves glucose metabolism independently of AMPK activation. J. Cell. Mol. Med. 22, 1316\u20131328. https:\/\/doi.org\/10.1111\/jcmm.13432 (2018).","journal-title":"J. Cell. Mol. Med."},{"key":"54865_CR22","doi-asserted-by":"publisher","first-page":"8516","DOI":"10.1074\/jbc.M210432200","volume":"278","author":"N Li","year":"2003","unstructured":"Li, N. et al. Mitochondrial complex I inhibitor rotenone induces apoptosis through enhancing mitochondrial reactive oxygen species production. J. Biol. Chem. 278, 8516\u20138525. https:\/\/doi.org\/10.1074\/jbc.M210432200 (2003).","journal-title":"J. Biol. Chem."},{"key":"54865_CR23","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1016\/j.biopha.2016.03.021","volume":"80","author":"M Paul-Samojedny","year":"2016","unstructured":"Paul-Samojedny, M. et al. Methylglyoxal (MGO) inhibits proliferation and induces cell death of human glioblastoma multiforme T98G and U87MG cells. Biomed. Pharmacother. 80, 236\u2013243. https:\/\/doi.org\/10.1016\/j.biopha.2016.03.021 (2016).","journal-title":"Biomed. Pharmacother"},{"key":"54865_CR24","doi-asserted-by":"publisher","first-page":"322","DOI":"10.1016\/j.bcp.2018.08.041","volume":"156","author":"A Roy","year":"2018","unstructured":"Roy, A. et al. Methylglyoxal at metronomic doses sensitizes breast cancer cells to doxorubicin and cisplatin causing synergistic induction of programmed cell death and inhibition of stemness. Biochem. Pharmacol. 156, 322\u2013339. https:\/\/doi.org\/10.1016\/j.bcp.2018.08.041 (2018).","journal-title":"Biochem. Pharmacol."},{"key":"54865_CR25","doi-asserted-by":"publisher","first-page":"129424","DOI":"10.1016\/j.foodchem.2021.129424","volume":"352","author":"P Liu","year":"2021","unstructured":"Liu, P. et al. Cytotoxicity of adducts formed between quercetin and methylglyoxal in PC-12 cells. Food Chem. 352, 129424. https:\/\/doi.org\/10.1016\/j.foodchem.2021.129424 (2021).","journal-title":"Food Chem."},{"key":"54865_CR26","doi-asserted-by":"publisher","first-page":"558","DOI":"10.1016\/j.apsb.2021.09.019","volume":"12","author":"D Du","year":"2022","unstructured":"Du, D. et al. Metabolic dysregulation and emerging therapeutical targets for hepatocellular carcinoma. Acta Pharm. Sin B. 12, 558\u2013580. https:\/\/doi.org\/10.1016\/j.apsb.2021.09.019 (2022).","journal-title":"Acta Pharm. Sin B"},{"key":"54865_CR27","doi-asserted-by":"publisher","first-page":"1400","DOI":"10.1016\/j.celrep.2020.01.012","volume":"30","author":"J Bellier","year":"2020","unstructured":"Bellier, J. et al. Methylglyoxal Scavengers Resensitize KRAS-Mutated Colorectal Tumors to Cetuximab. Cell. Rep. 30, 1400\u20131416e1406. https:\/\/doi.org\/10.1016\/j.celrep.2020.01.012 (2020).","journal-title":"Cell. Rep."},{"key":"54865_CR28","doi-asserted-by":"publisher","first-page":"e0126459","DOI":"10.1371\/journal.pone.0126459","volume":"10","author":"W Li","year":"2015","unstructured":"Li, W. et al. Shikonin Suppresses Skin Carcinogenesis via Inhibiting Cell Proliferation. PLoS One. 10, e0126459. https:\/\/doi.org\/10.1371\/journal.pone.0126459 (2015).","journal-title":"PLoS One"},{"key":"54865_CR29","doi-asserted-by":"publisher","first-page":"1276","DOI":"10.4103\/1673-5374.235076","volume":"13","author":"LX Liu","year":"2018","unstructured":"Liu, L. X. et al. Differences in brain pathological changes between rotenone and 6-hydroxydopamine Parkinson\u2019s disease models. Neural Regen Res. 13, 1276\u20131280. https:\/\/doi.org\/10.4103\/1673-5374.235076 (2018).","journal-title":"Neural Regen Res."},{"key":"54865_CR30","doi-asserted-by":"publisher","first-page":"703","DOI":"10.3390\/biom3030703","volume":"3","author":"BA Silva","year":"2013","unstructured":"Silva, B. A., Einarsdottir, O., Fink, A. L. & Uversky, V. N. Biophysical Characterization of alpha-Synuclein and Rotenone Interaction. Biomolecules 3, 703\u2013732. https:\/\/doi.org\/10.3390\/biom3030703 (2013).","journal-title":"Biomolecules"},{"key":"54865_CR31","doi-asserted-by":"publisher","first-page":"e017820","DOI":"10.1161\/JAHA.120.017820","volume":"9","author":"DJ Tyrrell","year":"2020","unstructured":"Tyrrell, D. J., Blin, M. G., Song, J., Wood, S. C. & Goldstein, D. R. Aging Impairs Mitochondrial Function and Mitophagy and Elevates Interleukin 6 Within the Cerebral Vasculature. J. Am. Heart Assoc. 9, e017820. https:\/\/doi.org\/10.1161\/JAHA.120.017820 (2020).","journal-title":"J. Am. Heart Assoc."},{"key":"54865_CR32","doi-asserted-by":"publisher","first-page":"1865","DOI":"10.1016\/j.freeradbiomed.2012.02.038","volume":"52","author":"Y Arimura","year":"2012","unstructured":"Arimura, Y. et al. Mitochondrial superoxide production contributes to vancomycin-induced renal tubular cell apoptosis. Free Radic Biol. Med. 52, 1865\u20131873. https:\/\/doi.org\/10.1016\/j.freeradbiomed.2012.02.038 (2012).","journal-title":"Free Radic Biol. Med."},{"key":"54865_CR33","doi-asserted-by":"publisher","first-page":"835","DOI":"10.3892\/ijo.2020.5089","volume":"57","author":"S Sudsaward","year":"2020","unstructured":"Sudsaward, S. et al. Endoplasmic reticulum stress, unfolded protein response and autophagy contribute to resistance to glucocorticoid treatment in human acute lymphoblastic leukaemia cells. Int. J. Oncol. 57, 835\u2013844. https:\/\/doi.org\/10.3892\/ijo.2020.5089 (2020).","journal-title":"Int. J. Oncol."},{"key":"54865_CR34","doi-asserted-by":"publisher","first-page":"6586","DOI":"10.1007\/s12035-019-1559-5","volume":"56","author":"JN He","year":"2019","unstructured":"He, J. N. et al. Rapamycin Removes Damaged Mitochondria and Protects Human Trabecular Meshwork (TM-1) Cells from Chronic Oxidative Stress. Mol. Neurobiol. 56, 6586\u20136593. https:\/\/doi.org\/10.1007\/s12035-019-1559-5 (2019).","journal-title":"Mol. Neurobiol."},{"key":"54865_CR35","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1016\/j.etap.2008.10.003","volume":"27","author":"S Swarnkar","year":"2009","unstructured":"Swarnkar, S., Tyagi, E., Agrawal, R., Singh, M. P. & Nath, C. A comparative study on oxidative stress induced by LPS and rotenone in homogenates of rat brain regions. Environ. Toxicol. Pharmacol. 27, 219\u2013224. https:\/\/doi.org\/10.1016\/j.etap.2008.10.003 (2009).","journal-title":"Environ. Toxicol. Pharmacol."},{"key":"54865_CR36","doi-asserted-by":"publisher","first-page":"870","DOI":"10.1089\/ars.2015.6539","volume":"25","author":"F Sotzny","year":"2016","unstructured":"Sotzny, F. et al. TCF11\/Nrf1-Mediated Induction of Proteasome Expression Prevents Cytotoxicity by Rotenone. Antioxid. Redox Signal. 25, 870\u2013885. https:\/\/doi.org\/10.1089\/ars.2015.6539 (2016).","journal-title":"Antioxid. Redox Signal."},{"key":"54865_CR37","doi-asserted-by":"publisher","first-page":"879","DOI":"10.1007\/s10495-019-01566-4","volume":"24","author":"M Wu","year":"2019","unstructured":"Wu, M. et al. Rotenone protects against beta-cell apoptosis and attenuates type 1 diabetes mellitus. Apoptosis 24, 879\u2013891. https:\/\/doi.org\/10.1007\/s10495-019-01566-4 (2019).","journal-title":"Apoptosis"},{"key":"54865_CR38","doi-asserted-by":"publisher","first-page":"112244","DOI":"10.1016\/j.fct.2021.112244","volume":"153","author":"D Tang","year":"2021","unstructured":"Tang, D. et al. Pterostilbene prevents methylglyoxal-induced cytotoxicity in endothelial cells by regulating glyoxalase, oxidative stress and apoptosis. Food Chem. Toxicol. 153, 112244. https:\/\/doi.org\/10.1016\/j.fct.2021.112244 (2021).","journal-title":"Food Chem. Toxicol."},{"key":"54865_CR39","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1196\/annals.1333.020","volume":"1043","author":"RH Nagaraj","year":"2005","unstructured":"Nagaraj, R. H., Oya-Ito, T., Bhat, M. & Liu, B. Dicarbonyl stress and apoptosis of vascular cells: prevention by alphaB-crystallin. Ann. N Y Acad. Sci. 1043, 158\u2013165. https:\/\/doi.org\/10.1196\/annals.1333.020 (2005).","journal-title":"Ann. N Y Acad. Sci."},{"key":"54865_CR40","doi-asserted-by":"publisher","first-page":"C68","DOI":"10.1152\/ajpcell.00117.2018","volume":"317","author":"Y Wang","year":"2019","unstructured":"Wang, Y. et al. Methylglyoxal triggers human aortic endothelial cell dysfunction via modulation of the K(ATP)\/MAPK pathway. Am. J. Physiol. Cell. Physiol. 317, C68\u2013C81. https:\/\/doi.org\/10.1152\/ajpcell.00117.2018 (2019).","journal-title":"Am. J. Physiol. Cell. Physiol."},{"key":"54865_CR41","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1074\/jbc.M116.743823","volume":"292","author":"DH Pfaff","year":"2017","unstructured":"Pfaff, D. H., Fleming, T., Nawroth, P. & Teleman, A. A. Evidence Against a Role for the Parkinsonism-associated Protein DJ-1 in Methylglyoxal Detoxification. J. Biol. Chem. 292, 685\u2013690. https:\/\/doi.org\/10.1074\/jbc.M116.743823 (2017).","journal-title":"J. Biol. Chem."},{"key":"54865_CR42","doi-asserted-by":"publisher","first-page":"1883","DOI":"10.7150\/ijbs.27854","volume":"14","author":"Y Wang","year":"2018","unstructured":"Wang, Y. et al. PKM2 Inhibitor Shikonin Overcomes the Cisplatin Resistance in Bladder Cancer by Inducing Necroptosis. Int. J. Biol. Sci. 14, 1883\u20131891. https:\/\/doi.org\/10.7150\/ijbs.27854 (2018).","journal-title":"Int. J. Biol. Sci."},{"key":"54865_CR43","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1016\/j.canlet.2019.04.033","volume":"459","author":"JC Boulos","year":"2019","unstructured":"Boulos, J. C., Rahama, M., Hegazy, M. F. & Efferth, T. Shikonin derivatives for cancer prevention and therapy. Cancer Lett. 459, 248\u2013267. https:\/\/doi.org\/10.1016\/j.canlet.2019.04.033 (2019).","journal-title":"Cancer Lett."},{"key":"54865_CR44","doi-asserted-by":"publisher","first-page":"840","DOI":"10.1111\/bph.14129","volume":"175","author":"Y Zhang","year":"2018","unstructured":"Zhang, Y. et al. Shikonin inhibits myeloid differentiation protein 2 to prevent LPS-induced acute lung injury. Br. J. Pharmacol. 175, 840\u2013854. https:\/\/doi.org\/10.1111\/bph.14129 (2018).","journal-title":"Br. J. Pharmacol."},{"key":"54865_CR45","doi-asserted-by":"publisher","first-page":"154035","DOI":"10.1016\/j.phymed.2022.154035","volume":"99","author":"G Shu","year":"2022","unstructured":"Shu, G. et al. Preparation of shikonin liposome and evaluation of its in vitro antibacterial and in vivo infected wound healing activity. Phytomedicine 99, 154035. https:\/\/doi.org\/10.1016\/j.phymed.2022.154035 (2022).","journal-title":"Phytomedicine"},{"key":"54865_CR46","doi-asserted-by":"publisher","first-page":"104463","DOI":"10.1016\/j.phrs.2019.104463","volume":"149","author":"C Guo","year":"2019","unstructured":"Guo, C. et al. Pharmacological properties and derivatives of shikonin-A review in recent years. Pharmacol. Res. 149, 104463. https:\/\/doi.org\/10.1016\/j.phrs.2019.104463 (2019).","journal-title":"Pharmacol. Res."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-54865-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-54865-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-54865-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T13:04:37Z","timestamp":1786367077000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-54865-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,30]]},"references-count":46,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["54865"],"URL":"https:\/\/doi.org\/10.1038\/s41598-026-54865-7","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,30]]},"assertion":[{"value":"24 February 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 May 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 May 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The permission of animal use were approved by the Institutional Animal Care and Use Committee of North Sichuan Medical College (approval number NSMC 2024108) and conducted in accordance with ARRIVE guidelines 2.0 and the NIH Guide for the Care and Use of Laboratory Animals. All animal experiments strictly complied with the institutional pain management protocols, and pre-defined study endpoints and humane endpoints were strictly implemented to ensure the welfare of experimental animals.","order":2,"name":"Ethics","label":"Ethics statement","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"24690"}}