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Chrysin alleviates pressure overload-induced myocardial remodeling through regulating the PI3K/AKT/NRF2 pathway-mediated oxidative stress response
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Yijia Wang1, Xing Feng1, Shuhui Zhao1, Yuchong Fu1, Ao Zhang1, Xiaofeng Shen2, Bowen Yu2, Yihao Wang2, Jiahui Lin2, Bing Zhang3, Weiping Ji2, 4, Lianpin Wu5, 6, Xiaoling Guo1, 5, 6
Animal Models and Experimental Medicine | 2026, 9(7) : 1373 - 1394
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Animal Models and Experimental Medicine | 2026, 9(7): 1373-1394
• Regular Articles •
Chrysin alleviates pressure overload-induced myocardial remodeling through regulating the PI3K/AKT/NRF2 pathway-mediated oxidative stress response
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Yijia Wang1, Xing Feng1, Shuhui Zhao1, Yuchong Fu1, Ao Zhang1, Xiaofeng Shen2, Bowen Yu2, Yihao Wang2, Jiahui Lin2, Bing Zhang3, Weiping Ji2, 4, Lianpin Wu5, 6, Xiaoling Guo1, 5, 6
Affiliations
  • 1Basic Medical Research Center, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China
  • 2Department of General Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China
  • 3Engineering Research Center of Techniques and Instruments for Diagnosis and Treatment of Congenital Heart Disease, Institute of Developmental and Regenerative Medicine, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
  • 4National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
  • 5Zhejiang-Ireland Joint Laboratory for Precision Diagnosis and Treatment of Valvular Heart Diseases, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
  • 6Department of Cardiology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
Published: 2026-07-28 doi: 10.1002/ame2.70230
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Background:

Oxidative stress plays a pivotal role in the pathogenesis of heart failure and is closely linked to myocardial remodeling, which includes myocardial hypertrophy and fibrosis. Chrysin (CHR) has multiple medicinal effects such as antioxidant, anti-inflammatory, and anti-apoptosis. This research seeks to investigate whether CHR can protect against pressure overload-induced myocardial remodeling and to explore the underlying mechanism.

Methods:

Transverse aortic constriction (TAC) surgery was conducted to establish a model of cardiac hypertrophy on male C57BL/6J mice. A model of cardiomyocyte hypertrophy in H9C2 cells induced by angiotensin II (Ang II) was also established.

Results:

The results showed that CHR significantly improved survival and cardiac function, reduced myocardial hypertrophy and fibrosis, inhibited the expression of inflammatory mediators TNF-α and IL-1β, suppressed cell apoptosis rate, downregulated the levels of Bcl-2 Associated X protein (BAX) and Cleaved-Caspase-3, and upregulated B-cell lymphoma/leukemia 2 (BCL-2) expression in TAC surgical mice or AngⅡ-treated H9C2 cells. CHR could also upregulate the levels of antioxidant enzymes SOD1 and HO-1 by mediating the nuclear translocation and expression of NRF2 to counteract oxidative stress response. The further mechanism investigation utilizing bioinformatics analysis and western blot revealed that the disease of heart failure is associated with the phosphatidylinositol-3-kinase (PI3K)/serine/threonine-protein kinase B (AKT) signaling pathway.

Conclusions:

Collectively, our findings demonstrated that CHR might exert the improvement effects on pressure overload-induced myocardial remodeling with hypertrophy and fibrosis through regulating the PI3K/AKT/NRF2 pathway-mediated oxidative stress response to alleviate myocardial cell inflammation and apoptosis, suggesting that CHR may be a promising therapeutic agent for cardiac diseases induced by pressure overload.

apoptosis  /  chrysin  /  inflammation  /  myocardial remodeling  /  oxidative stress
Yijia Wang, Xing Feng, Shuhui Zhao, Yuchong Fu, Ao Zhang, Xiaofeng Shen, Bowen Yu, Yihao Wang, Jiahui Lin, Bing Zhang, Weiping Ji, Lianpin Wu, Xiaoling Guo. Chrysin alleviates pressure overload-induced myocardial remodeling through regulating the PI3K/AKT/NRF2 pathway-mediated oxidative stress response[J]. Animal Models and Experimental Medicine, 2026 , 9 (7) : 1373 -1394 . DOI: 10.1002/ame2.70230
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Funding
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  • The Key Research and Development Program of Zhejiang Province(2023C03018)
  • Natural Science Foundation of Zhejiang Province(LY24H020008)
  • Jie Bang Gua Shuai Project of Wenzhou Science and Technology Bureau(ZY2023022; ZY2024019)
Appendix
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Year 2026 volume 9 Issue 7
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35
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Article Info
doi: 10.1002/ame2.70230
  • Receive Date：2026-01-11
  • Online Date：2026-08-06
  • Published：2026-07-28
Article Data
Affiliations
History
  • Received：2026-01-11
  • Revised：2026-03-31
  • Accepted：2026-05-03
Funding
The Key Research and Development Program of Zhejiang Province(2023C03018)
Natural Science Foundation of Zhejiang Province(LY24H020008)
Jie Bang Gua Shuai Project of Wenzhou Science and Technology Bureau(ZY2023022; ZY2024019)
Affiliations
    1Basic Medical Research Center, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China
    2Department of General Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China
    3Engineering Research Center of Techniques and Instruments for Diagnosis and Treatment of Congenital Heart Disease, Institute of Developmental and Regenerative Medicine, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
    4National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
    5Zhejiang-Ireland Joint Laboratory for Precision Diagnosis and Treatment of Valvular Heart Diseases, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
    6Department of Cardiology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, China

Corresponding:

Weiping Ji, Department of General Surgery, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China. Email:
Lianpin Wu, Zhejiang-Ireland Joint Laboratory for Precision Diagnosis and Treatment of Valvular Heart Diseases, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China. Email:
Xiaoling Guo, Basic Medical Research Center, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, 109 Xueyuan West Road, Wenzhou 325027, Zhejiang, China. Email:
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表12种不同金属材料的力学参数
科
Family		 属数
Number of
genus		 种数
Number of
species		 占总种数比例
Percentage of
total species (%)		 属
Genus		 种数
Number of
species		 占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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