{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:46:52Z","timestamp":1785422812660,"version":"3.56.0"},"reference-count":30,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T00:00:00Z","timestamp":1774915200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Heilongjiang Chinese Medicine Administration","award":["ZHY2024-094"],"award-info":[{"award-number":["ZHY2024-094"]}]},{"DOI":"10.13039\/501100003851","name":"Heilongjiang Provincial Department of Education","doi-asserted-by":"publisher","award":["2024-KYYWF-0612"],"award-info":[{"award-number":["2024-KYYWF-0612"]}],"id":[{"id":"10.13039\/501100003851","id-type":"DOI","asserted-by":"publisher"}]},{"award":["2024-KYYWF-0612"],"award-info":[{"award-number":["2024-KYYWF-0612"]}],"id":[{"id":"https:\/\/ror.org\/04rn1rm44","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014902","name":"Jiamusi University","doi-asserted-by":"publisher","award":["DJXSTD202409"],"award-info":[{"award-number":["DJXSTD202409"]}],"id":[{"id":"10.13039\/501100014902","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014902","name":"Jiamusi University","doi-asserted-by":"publisher","award":["JMSUGPZR2023-013"],"award-info":[{"award-number":["JMSUGPZR2023-013"]}],"id":[{"id":"10.13039\/501100014902","id-type":"DOI","asserted-by":"publisher"}]},{"award":["DJXSTD202409"],"award-info":[{"award-number":["DJXSTD202409"]}],"id":[{"id":"https:\/\/ror.org\/01vasff55","id-type":"ROR","asserted-by":"publisher"}]},{"award":["JMSUGPZR2023-013"],"award-info":[{"award-number":["JMSUGPZR2023-013"]}],"id":[{"id":"https:\/\/ror.org\/01vasff55","id-type":"ROR","asserted-by":"publisher"}]},{"name":"First Affiliated Hospital of Jiamusi University","award":["202302"],"award-info":[{"award-number":["202302"]}]},{"award":["202302"],"award-info":[{"award-number":["202302"]}],"id":[{"id":"https:\/\/ror.org\/01djnt473","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005046","name":"Heilongjiang Provincial Natural Science Foundation of China","doi-asserted-by":"crossref","award":["LH2024H005"],"award-info":[{"award-number":["LH2024H005"]}],"id":[{"id":"10.13039\/501100005046","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Myocardial ischemia\u2013reperfusion injury (MIRI) significantly compromises the clinical benefits of revascularization and constitutes a central pathological mechanism worsening prognosis in myocardial infarction patients. Accordingly, dissecting the molecular mechanisms underlying MIRI and formulating effective therapeutic interventions are of great clinical significance. Lycium barbarum polysaccharide (LBP), the primary active constituent of Lycium barbarum, has garnered considerable attention in the prevention and treatment of cardiovascular diseases due to its anti-inflammatory, antioxidant, vasomotor function-improving, and antithrombotic properties. This study aims to investigate the ability of LBP to alleviate MIRI, with a specific focus on its role in modulating the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome. Myocardial ischemia\/reperfusion (I\/R) models in rats and hypoxia\/reoxygenation (H\/R) models in H9c2 cells were established. Myocardial injury and the therapeutic effect of LBP were evaluated by 2,3,5-Triphenyl tetrazolium chloride (TTC) staining, Hematoxylin-eosin (H&amp;E) staining, Terminal deoxynucleotidyl transferase dUTP Nick-End Labeling (TUNEL) staining, and Enzyme-linked immunosorbent assay (ELISA). To elucidate the specific mechanism underlying LBP against MIRI, an Nrf2-overexpressing cell line was generated in H9c2 cells, and pharmacological inhibition of Nrf2 with ML385 was applied for complementary validation. The effects of LBP on H\/R-induced oxidative stress, inflammatory response (IL-18, IL-1\u03b2), and pyroptosis-related protein expression (NLRP3, apoptosis associated speck-like protein containing a CARD (ASC), cysteine-dependent aspartate-specific proteases (caspase)-1, Gasdermin D (GSDMD)) were systematically evaluated. LBP administration conferred robust cardioprotection in I\/R rats, as evidenced by a significant reduction in myocardial infarct size, improved preservation of myocardial fiber architecture, and attenuated leakage of cardiac injury biomarkers (lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB)). Mirroring these in vivo findings, LBP pretreatment effectively shielded H9c2 cardiomyocytes from H\/R insult, markedly enhancing cell viability while curtailing reactive oxygen species (ROS) accumulation and apoptotic activation. A pivotal finding was the pronounced downregulation of Nrf2 in the H\/R group, a deficit that was conclusively reversed by LBP treatment. To decisively establish a causal role for Nrf2, we employed a loss-of-function approach; Nrf2 inhibition completely abrogated the protective benefits of LBP, culminating in exacerbated tissue damage, a surge in ROS, and the upregulation of key pyroptosis effectors (NLRP3, ASC, caspase-1, GSDMD). Conversely, a complementary gain-of-function experiment demonstrated that Nrf2 overexpression alone was sufficient to mimic LBP\u2019s effects, significantly blunting H\/R-induced ROS production and pyroptosis. LBP alleviates MIRI by inhibiting pyroptosis through activating the Nrf2\/NLRP3 axis, thus representing a promising therapeutic candidate for ischemic heart disease with the potential to improve patient outcomes.<\/jats:p>","DOI":"10.3390\/ijms27073198","type":"journal-article","created":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T08:08:34Z","timestamp":1775030914000},"page":"3198","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Lycium Barbarum Polysaccharide Antagonizes Cardiomyocyte Pyroptosis by Inhibiting the Nrf2\/NLRP3 Signal Pathway Against Myocardial Ischemia\u2013Reperfusion Injury"],"prefix":"10.3390","volume":"27","author":[{"given":"Liuxin","family":"Wu","sequence":"first","affiliation":[{"name":"School of Pharmaceutical Sciences, Jiamusi University, Jiamusi 154003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Lin","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Jiamusi University, Jiamusi 154003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomeng","family":"Yin","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Jiamusi University, Jiamusi 154003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Jiamusi University, Jiamusi 154003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyan","family":"Ma","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Jiamusi University, Jiamusi 154003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shulin","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Jiamusi University, Jiamusi 154003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moyan","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Jiamusi University, Jiamusi 154003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangyuan","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Jiamusi University, Jiamusi 154003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingyuan","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Jiamusi University, Jiamusi 154003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"155649","DOI":"10.1016\/j.phymed.2024.155649","article-title":"The pathological mechanisms and potential therapeutic drugs for myocardial ischemia reperfusion injury","volume":"129","author":"Zhang","year":"2024","journal-title":"Phytomedicine"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e3","DOI":"10.1161\/CIRCRESAHA.121.318992","article-title":"CIRKIL Exacerbates Cardiac Ischemia\/Reperfusion Injury by Interacting with Ku70","volume":"130","author":"Xiao","year":"2022","journal-title":"Circ. 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