{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T13:09:13Z","timestamp":1779196153671,"version":"3.51.4"},"reference-count":38,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:00:00Z","timestamp":1779148800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical and Health Science Program of Zhejiang Province","award":["2024KY924"],"award-info":[{"award-number":["2024KY924"]}]},{"name":"Medical and Health Science Program of Zhejiang Province","award":["2023KY708"],"award-info":[{"award-number":["2023KY708"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Background: Pyrroloquinoline quinone (PQQ), a naturally occurring redox cofactor with potent antioxidant and anti-inflammatory properties, has been shown to protect against cardiac injury. However, its therapeutic potential in diabetic cardiomyopathy (DCM) induced by Type 2 diabetes mellitus (T2DM) and the underlying mechanisms remain poorly understood. Methods: A T2DM mouse model was established via a high-fat diet and low-dose STZ. We investigated the cardioprotective effects of 12-week oral PQQ administration, assessing fasting blood glucose, oral glucose tolerance, cardiac function, myocardial histopathology, blood biochemistry, mitophagy, and NLRP3 inflammasome activation. In vitro experiments using AC16 cardiomyocytes exposed to palmitic acid and high glucose were also conducted. Results: Results showed PQQ significantly improved cardiac function, attenuated remodeling, and reduced proinflammatory cytokines in mice with T2DM, regulated key mitophagy-related proteins (Parkin, Beclin-1, LC3B-II, p62), and downregulated NLRP3 inflammasome pathway components (Caspase-1, NLRP3, IL-1\u03b2, IL-18). In vitro experiments demonstrated that PQQ reduced reactive oxygen species (ROS) production, improved mitochondrial membrane potential, promoted mitophagy, and inhibited NLRP3 inflammasome-mediated pyroptosis. Conclusions: PQQ alleviates DCM in mice with T2DM by improving mitochondrial quality control, promoting mitophagy, and subsequently inhibiting NLRP3 inflammasome-mediated pyroptosis, highlighting its potential as a promising therapeutic agent for T2DM-associated cardiomyopathy.<\/jats:p>","DOI":"10.3390\/metabo16050340","type":"journal-article","created":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T11:53:10Z","timestamp":1779191590000},"page":"340","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pyrroloquinoline Quinone Mitigates Type 2 Diabetes-Induced Cardiac Injury Through Mitochondrial Quality Control and Inhibition of NLRP3-Dependent Pyroptosis"],"prefix":"10.3390","volume":"16","author":[{"given":"Xue","family":"Zhang","sequence":"first","affiliation":[{"name":"School of Pharmacy, School of Food Science and Engineering, Hangzhou Medical College, Hangzhou 310013, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Pharmacy, School of Food Science and Engineering, Hangzhou Medical College, Hangzhou 310013, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhijing","family":"Fu","sequence":"additional","affiliation":[{"name":"School of Pharmacy, School of Food Science and Engineering, Hangzhou Medical College, Hangzhou 310013, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhuoling","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Pharmacy, School of Food Science and Engineering, Hangzhou Medical College, Hangzhou 310013, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qixin","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Pharmacy, School of Food Science and Engineering, Hangzhou Medical College, Hangzhou 310013, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanan","family":"Shen","sequence":"additional","affiliation":[{"name":"School of Pharmacy, School of Food Science and Engineering, Hangzhou Medical College, Hangzhou 310013, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yukai","family":"Jin","sequence":"additional","affiliation":[{"name":"School of Pharmacy, School of Food Science and Engineering, Hangzhou Medical College, Hangzhou 310013, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dengfeng","family":"Xu","sequence":"additional","affiliation":[{"name":"School of Pharmacy, School of Food Science and Engineering, Hangzhou Medical College, Hangzhou 310013, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yin","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, School of Food Science and Engineering, Hangzhou Medical College, Hangzhou 310013, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuefeng","family":"Qu","sequence":"additional","affiliation":[{"name":"School of Pharmacy, School of Food Science and Engineering, Hangzhou Medical College, Hangzhou 310013, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yangjunna","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, School of Food Science and Engineering, Hangzhou Medical College, Hangzhou 310013, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1080\/09168451.2015.1062715","article-title":"Recent progress in studies on the health benefits of pyrroloquinoline quinone","volume":"80","author":"Akagawa","year":"2016","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"5276","DOI":"10.7150\/ijbs.75402","article-title":"Mitochondrial quality control in diabetic cardiomyopathy: From molecular mechanisms to therapeutic strategies","volume":"18","author":"Cai","year":"2022","journal-title":"Int. J. Biol. Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1038\/s41401-020-0487-2","article-title":"Pyrroloquinoline quinone promotes mitochondrial biogenesis in rotenone-induced Parkinson\u2019s disease model via AMPK activation","volume":"42","author":"Cheng","year":"2021","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1021\/acs.chemrestox.1c00340","article-title":"Pyrroloquinoline Quinone Chemistry, Biology, and Biosynthesis","volume":"35","author":"Cordell","year":"2022","journal-title":"Chem. Res. Toxicol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Dabravolski, S.A., Sadykhov, N.K., Kartuesov, A.G., Borisov, E.E., Sukhorukov, V.N., and Orekhov, A.N. (2022). The Role of Mitochondrial Abnormalities in Diabetic Cardiomyopathy. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23147863"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1161\/CIRCRESAHA.118.314665","article-title":"Diabetic Cardiomyopathy","volume":"124","author":"Dillmann","year":"2019","journal-title":"Circ. Res."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Doblado, L., Lueck, C., Rey, C., Samhan-Arias, A.K., Prieto, I., Stacchiotti, A., and Monsalve, M. (2021). Mitophagy in Human Diseases. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22083903"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"110178","DOI":"10.1016\/j.jnutbio.2025.110178","article-title":"Protective effects of pyrroloquinoline quinone in CNS disorders","volume":"149","author":"Aboulhassane","year":"2026","journal-title":"J. Nutr. Biochem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1007\/s11033-025-10491-6","article-title":"Current study on Pyrroloquinoline quinone (PQQ) therapeutic role in neurodegenerative diseases","volume":"52","author":"Xie","year":"2025","journal-title":"Mol. Biol. Rep."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e404","DOI":"10.1038\/emm.2017.199","article-title":"Nanocurcumin-pyrroloquinoline formulation prevents hypertrophy-induced pathological damage by relieving mitochondrial stress in cardiomyocytes under hypoxic conditions","volume":"49","author":"Nehra","year":"2017","journal-title":"Exp. Mol. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"102379","DOI":"10.1016\/j.cpcardiol.2024.102379","article-title":"COMMENT ON \u201cRevisiting Beta-Blocker Therapy in Heart Failure with Preserved Ejection Fraction\u201d, Current Problems in Cardiology (2023), doi: https:\/\/doi.org\/10.1016\/j.cpcardiol.2023.102203","volume":"49","author":"Kaddoura","year":"2024","journal-title":"Curr. Probl. Cardiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.1007\/s00394-021-02768-w","article-title":"Pyrroloquinoline quinone ameliorates diabetic cardiomyopathy by inhibiting the pyroptosis signaling pathway in C57BL\/6 mice and AC16 cells","volume":"61","author":"Qu","year":"2022","journal-title":"Eur. J. Nutr."},{"key":"ref_13","first-page":"268","article-title":"Potential physiological importance of pyrroloquinoline quinone","volume":"14","author":"Rucker","year":"2009","journal-title":"Altern. Med. Rev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.bbrc.2012.10.055","article-title":"Pyrroloquinoline quinone, a novel protein tyrosine phosphatase 1B inhibitor, activates insulin signaling in C2C12 myotubes and improves impaired glucose tolerance in diabetic KK-A(y) mice","volume":"428","author":"Takada","year":"2012","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1038\/s41419-023-06162-8","article-title":"Pyrroloquinoline quinone inhibits PCSK9-NLRP3 mediated pyroptosis of Leydig cells in obese mice","volume":"14","author":"Wang","year":"2023","journal-title":"Cell Death Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/j.intimp.2019.04.040","article-title":"Protective effects of pyrroloquinoline quinine against oxidative stress-induced cellular senescence and inflammation in human renal tubular epithelial cells via Keap1\/Nrf2 signaling pathway","volume":"72","author":"Wang","year":"2019","journal-title":"Int. Immunopharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1146\/annurev.nu.10.070190.001501","article-title":"The cofactor pyrroloquinoline quinone","volume":"10","author":"Duine","year":"1990","journal-title":"Annu. Rev. Nutr."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"153319","DOI":"10.1016\/j.phymed.2020.153319","article-title":"Isoliquiritigenin attenuates diabetic cardiomyopathy via inhibition of hyperglycemia-induced inflammatory response and oxidative stress","volume":"78","author":"Gu","year":"2020","journal-title":"Phytomedicine"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1186\/s12933-023-01816-5","article-title":"Insights into SGLT2 inhibitor treatment of diabetic cardiomyopathy: Focus on the mechanisms","volume":"22","author":"Huang","year":"2023","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Jonscher, K.R., Chowanadisai, W., and Rucker, R.B. (2021). Pyrroloquinoline-Quinone Is More Than an Antioxidant: A Vitamin-like Accessory Factor Important in Health and Disease Prevention. Biomolecules, 11.","DOI":"10.3390\/biom11101441"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1434","DOI":"10.1096\/fj.201600906R","article-title":"Early PQQ supplementation has persistent long-term protective effects on developmental programming of hepatic lipotoxicity and inflammation in obese mice","volume":"31","author":"Jonscher","year":"2017","journal-title":"FASEB J."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1038\/ni0311-199","article-title":"Mitochondrial control of the NLRP3 inflammasome","volume":"12","author":"Kepp","year":"2011","journal-title":"Nat. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1042\/bj3070331","article-title":"Levels of pyrroloquinoline quinone in various foods","volume":"307","author":"Kumazawa","year":"1995","journal-title":"Biochem. J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/0304-4165(92)90096-D","article-title":"Trace levels of pyrroloquinoline quinone in human and rat samples detected by gas chromatography\/mass spectrometry","volume":"1156","author":"Kumazawa","year":"1992","journal-title":"Biochim. Biophys. Acta (BBA)-Gen. Subj."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"106823","DOI":"10.1016\/j.intimp.2020.106823","article-title":"Chebulanin exerts its anti-inflammatory and anti-arthritic effects via inhibiting NF-\u03baB and MAPK activation in collagen-induced arthritis mice","volume":"88","author":"Liu","year":"2020","journal-title":"Int. Immunopharmacol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Luo, B., Li, B., Wang, W., Liu, X., Xia, Y., Zhang, C., Zhang, M., Zhang, Y., and An, F. (2014). NLRP3 gene silencing ameliorates diabetic cardiomyopathy in a type 2 diabetes rat model. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0104771"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/S1097-2765(02)00599-3","article-title":"The inflammasome: A molecular platform triggering activation of inflammatory caspases and processing of proIL-beta","volume":"10","author":"Martinon","year":"2002","journal-title":"Mol. Cell"},{"key":"ref_28","unstructured":"(2018). Laboratory Animal\u2014Guideline for Ethical Review of Animal Welfare (Standard No. GB\/T 35892-2018)."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e78","DOI":"10.1002\/cpz1.78","article-title":"Streptozotocin-Induced Diabetic Models in Mice and Rats","volume":"1","author":"Furman","year":"2021","journal-title":"Curr. Protoc."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"101058","DOI":"10.1016\/j.molmet.2020.101058","article-title":"Reappraisal of the optimal fasting time for insulin tolerance tests in mice","volume":"42","author":"Carper","year":"2020","journal-title":"Mol. Metab."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1038\/nature04515","article-title":"Cryopyrin activates the inflammasome in response to toxins and ATP","volume":"440","author":"Mariathasan","year":"2006","journal-title":"Nature"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1916","DOI":"10.4239\/wjd.v15.i9.1916","article-title":"Corilagin alleviates podocyte injury in diabetic nephropathy by regulating autophagy via the SIRT1-AMPK pathway","volume":"15","author":"Lou","year":"2024","journal-title":"World J. Diabetes"},{"key":"ref_33","first-page":"873","article-title":"Pyrroloquinoline quinone attenuates isoproterenol hydrochloride-induced cardiac hypertrophy in AC16 cells by inhibiting the NF-\u03baB signaling pathway","volume":"45","author":"Wen","year":"2020","journal-title":"Int. J. Mol. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"100889","DOI":"10.1016\/j.crfs.2024.100889","article-title":"Pyrroloquinoline Quinone (PQQ): Its impact on human health and potential benefits: PQQ: Human health impacts and benefits","volume":"9","author":"Yan","year":"2024","journal-title":"Curr. Res. Food Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2022","DOI":"10.1161\/CIRCULATIONAHA.118.038868","article-title":"Comparison of the Effects of Glucagon-Like Peptide Receptor Agonists and Sodium-Glucose Cotransporter 2 Inhibitors for Prevention of Major Adverse Cardiovascular and Renal Outcomes in Type 2 Diabetes Mellitus","volume":"139","author":"Zelniker","year":"2019","journal-title":"Circulation"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"103331","DOI":"10.1016\/j.drudis.2022.07.016","article-title":"Current and future approaches for in vitro hit discovery in diabetes mellitus","volume":"27","author":"Zhang","year":"2022","journal-title":"Drug Discov. Today"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1111\/dom.15369","article-title":"FOXO1 reduces STAT3 activation and causes impaired mitochondrial quality control in diabetic cardiomyopathy","volume":"26","author":"Zhou","year":"2024","journal-title":"Diabetes Obes. Metab."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2117","DOI":"10.1056\/NEJMoa1504720","article-title":"Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes","volume":"373","author":"Zinman","year":"2015","journal-title":"N. Engl. J. Med."}],"container-title":["Metabolites"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-1989\/16\/5\/340\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T12:28:01Z","timestamp":1779193681000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-1989\/16\/5\/340"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,19]]},"references-count":38,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["metabo16050340"],"URL":"https:\/\/doi.org\/10.3390\/metabo16050340","relation":{},"ISSN":["2218-1989"],"issn-type":[{"value":"2218-1989","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,19]]}}}