ZHANG Xinru,JIANG Zhonghui,GAO Zhuye,et al.Effects and mechanisms of kurarinone on myocardial remodeling induced by cardiac ischemia⁃reperfusion[J].Medical Journal of Wuhan University,2026,47(10):1295-1301.
ZHANG Xinru,JIANG Zhonghui,GAO Zhuye,et al.Effects and mechanisms of kurarinone on myocardial remodeling induced by cardiac ischemia⁃reperfusion[J].Medical Journal of Wuhan University,2026,47(10):1295-1301.DOI: 10.14188/j.1671-8852.2025.1458.
Effects and mechanisms of kurarinone on myocardial remodeling induced by cardiac ischemia⁃reperfusion
To explore the effect and molecular mechanism of kurarinone (KAR) on myocardial remodeling induced by myocardial ischemia‑reperfusion injury (MIRI).
Methods
2
Mouse models of myocardial ischemia‑reperfusion (I/R) were constructed
and the mice were randomly divided into four groups: sham operation + vehicle group (Sham+Veh)
sham operation + KAR group (Sham+KAR)
I/R + vehicle group (I/R+Veh)
and I/R + KAR group (I/R+KAR). The endpoint was set at 7 days after sham or I/R operation
and mouse hearts and serum were collected for pathological and biochemical analysis. Gross cardiac morphology and cardiac function were assessed. Commercial assay kits were used to detect serum levels of myocardial injury markers. HE staining and wheat germ agglutinin (WGA) staining were used to observe cardiomyocyte morphological changes. Picro sirius red (PSR) staining was used to evaluate the degree of myocardial fibrosis. TUNEL staining was used to assess cardiomyocyte apoptosis. Western blot was used to detect the expression of myocardial oxidative stress‑related proteins.
Results
2
KAR significantly improved cardiac function and reduced infarct size in mice after MIRI (
P
<
0.05)
alleviated myocardial structural damage and attenuated cardiac remodeling (
P
<
0.05)
and decreased oxidative stress and cardiomyocyte apoptosis (
P
<
0.05). Mechanistically
KAR promoted the expression of downstream antioxidant genes SOD2 and HO‑1 by upregulating Nrf2 protein expression.
Conclusion
2
Kurarinone ameliorates myocardial remodeling and oxidative stress injury after myocardial ischemia‑reperfusion by regulating the Nrf2/HO‑1 pathway.
关键词
Keywords
references
WANG L , LI D D , YAO F , et al . Serpina3k lactylation protects from cardiac ischemia reperfusion injury [J ] . Nat Commun , 2025 , 16 ( 1 ): 1012 .
BURKE R M , BURGOS VILLAR K N , SMALL E M . Fibroblast contributions to ischemic cardiac remodeling [J ] . Cell Signal , 2021 , 77 : 109824 .
WU X K , REBOLL M R , KORF‑KLINGEBIEL M , et al . Angiogenesis after acute myocardial infarction [J ] . Cardiovasc Res , 2021 , 117 ( 5 ): 1257 ‑ 1273 .
KURA B , SZEIFFOVA BACOVA B , KALOCAYOVA B , et al . Oxidative stress‑responsive microRNAs in heart injury [J ] . Int J Mol Sci , 2020 , 21 ( 1 ): 358 .
YAZAL T , LEE P Y , CHEN P R , et al . Kurarinone exerts anti‑inflammatory effect via reducing ROS production, suppressing NLRP3 inflammasome, and protecting against LPS‑induced sepsis [J ] . Biomed Pharmacother , 2023 , 167 : 115619 .
KWON M , OH T , JANG M , et al . Kurarinone induced p53‑independent G 0 /G 1 cell cycle arrest by degradation of K‑RAS via WDR76 in human colorectal cancer cells [J ] . Eur J Pharmacol , 2022 , 923 : 174938 .
MIN J S , KIM D E , JIN Y H , et al . Kurarinone inhibits HCoV‑OC43 infection by impairing the virus‑induced autophagic flux in MRC‑5 human lung cells [J ] . J Clin Med , 2020 , 9 ( 7 ): 2230 .
NISHIKAWA S , INOUE Y , HORI Y , et al . Anti‑inflammatory activity of kurarinone involves induction of HO‑1 via the KEAP1/Nrf2 pathway [J ] . Antioxidants , 2020 , 9 ( 9 ): 842 .
LU Q B , SUN H T , ZHOU K , et al . Therapeutic targeting of Decr1 ameliorates cardiomyopathy by suppressing mitochondrial fatty acid oxidation in diabetic mice [J ] . J Cachexia Sarcopenia Muscle , 2025 , 16 ( 2 ): e13761 .
YANG X X , SHI T T , MU J K , et al . Protective effects of kurarinone and norkurarnone on cardiomyocytes of neonatal rats suffering from hypoxia/reoxygenation injury [J ] . Tradit Chin Drug Res Clin Pharmacol , 2019 , 30 ( 7 ): 761 ‑ 765 .
GBD 2019 Diseases and Injuries Collaborators . Global burden of 369 diseases and injuries in 204 countries and territories, 1990‑2019: A systematic analysis for the Global Burden of Disease Study 2019 [J ] . Lancet , 2020 , 396 ( 10258 ): 1204 ‑ 1222 .
ZHANG Z Y , YANG Z H , WANG S , et al . Targeting MAPK‑ERK/JNK pathway: A potential intervention mechanism of myocardial fibrosis in heart failure [J ] . Biomed Pharmacother , 2024 , 173 : 116413 .
TANG K T , LIN C C , LIN S C , et al . Kurarinone attenuates collagen‑induced arthritis in mice by inhibiting Th1/Th17 cell responses and oxidative stress [J ] . Int J Mol Sci , 2021 , 22 ( 8 ): 4002 .
WENG Z B , ZENG F , WANG M X , et al . Antimicrobial activities of lavandulylated flavonoids in Sophora flavences against methici llin‑resistant Staphylococcus aureus via membrane disruption [J ] . J Adv Res , 2024 , 57 : 197 ‑ 212 .
HE J F , LIU D Y , ZHAO L X , et al . Myocardial ischemia/reperfusion injury: Mechanisms of injury and implications for management (Review) [J ] . Exp Ther Med , 2022 , 23 ( 6 ): 430 .
CHEN Y , LIU C , ZHOU P , et al . Coronary endothelium No‑reflow injury is associated with ROS‑modified mitochondrial fission through the JNK‑Drp1 signaling pathway [J ] . Oxid Med Cell Longev , 2021 , 2021 ( 1 ): 6699516 .
LIU Z X , HAN X , YOU Y , et al . Shuangshen ningxin formula attenuates cardiac microvascular ischemia/reperfusion injury through improving mitochondrial function [J ] . J Ethnopharmacol , 2024 , 323 : 117690 .
CHEN W X , ZHANG Y , WANG Z X , et al . Dapagliflozin alleviates myocardial ischemia/reperfusion injury by reducing ferroptosis via MAPK signaling inhibition [J ] . Front Pharmacol , 2023 , 14 : 1078205 .
LI H Y , YANG D H , ZHANG Y M , et al . Geniposide suppresses NLRP3 inflammasome‑mediated pyroptosis via the AMPK signaling pathway to mitigate myocardial ischemia/reperfusion injury [J ] . Chin Med , 2022 , 17 ( 1 ): 73 .
HEUSCH G . Myocardial ischemia/reperfusion: Translational pathophysiology of ischemic heart disease [J ] . Med , 2024 , 5 ( 1 ): 10 ‑ 31 .
XU S J , WU B X , ZHONG B Y , et al . Naringenin alleviates myocardial ischemia/reperfusion injury by regulating the nuclear factor‑erythroid factor 2‑related factor 2 (Nrf2)/System xc‑/ glutathione peroxidase 4 (GPX4) axis to inhibit ferroptosis [J ] . Bioengineered , 2021 , 12 ( 2 ): 1 0924‑ 10934 .
WANG L Y , LIU J , WANG Z R , et al . Dexmedetomidine abates myocardial ischemia reperfusion injury through inhibition of pyroptosis via regulation of miR‑665/MEF2D/Nrf2 axis [J ] . Biomed Pharmacother , 2023 , 165 : 115255 .
WANG Z R , YAO M R , JIANG L Y , et al . Dexmedetomidine attenuates myocardial ischemia/reperfusion‑induced ferroptosis via AMPK/GSK‑3β/Nrf2 axis [J ] . Biomed Pharmacother , 2022 , 154 : 113572 .
Mechanism and application of histone deacetylase inhibitors in cardiac remodeling
Research advance on the relationship between intestinal fungi and digestive system tumor
Advances in health education for venous thromboembolism prevention
Research progress on ADAMTS4 in acute lung injury/acute respiratory distress syndrome
Efficacy and safety of laparoscopic modified non⁃mesh iliopubic ligament suspension in the treatment of pelvic organ prolapse
Related Author
ZHANG Xinru
TANG Qizhu
ZHANG Xinru
KONG Chunyan
TANG Qizhu
ZHANG Xinru
KONG Chunyan
TANG Qizhu
Related Institution
Department of Cardiovascular Medicine, Renmin Hospital of Wuhan University & Hubei Provincial Key Laboratory of Metabolism and Related Chronic Diseases
Department of Cardiovascular Medicine, Renmin Hospital of Wuhan University & Hubei Provincial Key Laboratory of Metabolism and Related Chronic Diseases
Dept. of Cardiovascular Medicine, Renmin Hospital of Wuhan University & Hubei Provincial Key Laboratory of Metabolism and Related Chronic Diseases