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Qihuang Zhuyu Formula Attenuates Myocardial Ischemia Reperfusion Injury by Regulating Autophagy via the NF-κB
Siyuan Yin1,2,3, Manlu Fan4,5, Chunxiao Wang6
1Department of Cardiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China.
Introduction:
Myocardial Ischemia Reperfusion Injury (MIRI) contributes to adverse cardiovascular outcomes. Dysregulated myocardial autophagy plays a key role in MIRI, yet therapeutic strategies targeting this process are limited. Qihuang Zhuyu Formula (QHZYF), a traditional Chinese herbal compound, exhibits cardiovascular protective effects, but its molecular mechanism in MIRI remains unclear. The NF-κB P65/TRAIL signaling axis regulates autophagy in MIRI and may serve as a critical target for QHZYF intervention.
Methods:
QHZYF components were analyzed using UPLC-Q-TOF-MS. Network pharmacology identified the NF-κB P65/TRAIL pathway as a core mechanism. In vivo, a rat MIRI model was treated with QHZYF; myocardial injury was assessed via histology, electrocardiography, echocardiography, immunohistochemistry, western blot, and RT-qPCR. In vitro, H9C2 cells underwent hypoxia/reoxygenation and were treated with QHZYF. Autophagy and pathway-related markers, including NF-κB p65, TRAIL, Beclin 1, LC3, and P62, were measured.
Results:
Network pharmacology and experimental results confirmed that QHZYF targets NF-κB P65/TRAIL to restore myocardial autophagic homeostasis. Treatment reduced cardiomyocyte injury and normalized autophagy markers in both in vivo and in vitro models.
Discussion:
This study demonstrates that QHZYF exerts cardioprotective effects against MIRI by regulating autophagy and suppressing NF-κB P65/TRAIL signaling. Integration of compound analysis and experimental models revealed the pathway's key role in autophagic imbalance and myocardial injury. QHZYF intervention restored autophagic homeostasis and mitigated cardiomyocyte damage, highlighting its potential application for MIRI prevention and therapy.
Conclusion:
QHZYF alleviates myocardial autophagy imbalance via the NF-κB P65/TRAIL pathway, providing mechanistic insight into its therapeutic potential in MIRI management.
Insights
Qihuang Zhuyu Formula (QHZYF) protects the heart from injury after reperfusion by regulating autophagy. This traditional Chinese medicine targets the NF-κB P65/TRAIL pathway to restore cellular balance and reduce damage.
Area of Science:
- Cardiovascular Research
- Traditional Chinese Medicine
- Molecular Biology
Background:
- Myocardial Ischemia Reperfusion Injury (MIRI) leads to significant cardiovascular morbidity and mortality.
- Autophagy dysregulation is a critical factor in MIRI pathogenesis, yet effective therapeutic targets remain scarce.
- Qihuang Zhuyu Formula (QHZYF), a herbal compound, shows cardiovascular benefits, but its underlying molecular mechanisms in MIRI are not fully understood.
Purpose of the Study:
- To elucidate the molecular mechanism of QHZYF in mitigating MIRI.
- To investigate the role of the NF-κB P65/TRAIL signaling axis in QHZYF's cardioprotective effects.
- To evaluate QHZYF's ability to restore myocardial autophagic homeostasis.
Main Methods:
- Component analysis of QHZYF using UPLC-Q-TOF-MS.
- Network pharmacology to identify the NF-κB P65/TRAIL pathway as a key target.
- In vivo MIRI rat model and in vitro H9C2 cell models subjected to hypoxia/reoxygenation.
- Assessment of myocardial injury, autophagy markers (Beclin 1, LC3, P62), and pathway proteins (NF-κB p65, TRAIL) using histological, biochemical, and molecular techniques.
Main Results:
- QHZYF treatment significantly reduced cardiomyocyte injury and improved cardiac function in MIRI models.
- The NF-κB P65/TRAIL pathway was identified as a central target of QHZYF.
- QHZYF effectively normalized myocardial autophagy markers, restoring autophagic homeostasis in both in vivo and in vitro settings.
Conclusions:
- QHZYF demonstrates significant cardioprotective effects against MIRI by modulating autophagy.
- The therapeutic action of QHZYF is mediated through the suppression of the NF-κB P65/TRAIL signaling pathway.
- QHZYF represents a promising therapeutic strategy for managing MIRI by restoring autophagic balance and preventing cardiomyocyte damage.
