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Updated: Apr 21, 2026
Herbal Munziq Ameliorates Myocardial Ischemia-Reperfusion Injury by Inhibiting Inflammation
Published on: January 10, 2025
Targeting HMGB1 to Attenuate Myocardial Ischaemia-reperfusion Injury (MIRI)-induced Cognitive Dysfunction
Luyuan Yao1,2, Ye Sun1, Qinjun Chu3
1Department of Anesthesiology, The Second Affiliated Hospital of Dalian Medical University, Dalian, China.
Insights
Myocardial Ischaemia-Reperfusion Injury (MIRI) causes cognitive dysfunction via High-Mobility Group Box 1 (HMGB1). Targeting the HMGB1/Meteorin-like (Metrnl) interaction may offer a novel therapeutic strategy for MIRI-induced cognitive impairment.
Area of Science:
- Cardiovascular Research
- Neuroscience
- Immunology
Background:
- Myocardial Ischaemia-Reperfusion Injury (MIRI) is a significant cause of cognitive dysfunction.
- High-Mobility Group Box 1 (HMGB1) acts as a key mediator in the heart-brain axis during MIRI.
- HMGB1 triggers inflammation and neuroinflammation, disrupting the Blood-Brain Barrier (BBB) and leading to cognitive impairment.
Purpose of the Study:
- To review the role of HMGB1 in MIRI and associated cognitive dysfunction.
- To elucidate the potential interplay between HMGB1 and Meteorin-like (Metrnl).
- To explore the HMGB1/Metrnl antagonism as a therapeutic target for MIRI-induced cognitive impairment.
Main Methods:
- Literature review of recent studies on HMGB1, MIRI, and cognitive dysfunction.
- Analysis of the molecular mechanisms involving HMGB1, TLR2/4, RAGE, and BBB integrity.
- Investigation of the potential functional antagonism between HMGB1 and Metrnl.
Main Results:
- HMGB1, released during MIRI, activates inflammatory pathways (TLR2/4, RAGE).
- This activation leads to neuroinflammation, BBB disruption, microglial activation, and synaptic dysfunction.
- Emerging evidence suggests Metrnl plays a critical role in both MIRI and cognitive function.
Conclusions:
- The HMGB1/Metrnl functional antagonism presents a promising therapeutic avenue for MIRI-induced cognitive impairment.
- Targeting this interplay could mitigate long-term disability and reduce socioeconomic burdens associated with MIRI.
- Further research into the HMGB1/Metrnl axis is crucial for developing effective treatments.
Abstract:
Myocardial Ischaemia-Reperfusion Injury (MIRI) is increasingly recognized as a contributor to cognitive dysfunction, with High-Mobility Group Box 1 (HMGB1) serving as a pivotal mediator in this heart-brain axis. Released from damaged cardiomyocytes, HMGB1 acts as a Damage-Associated Molecular Pattern (DAMP), activating Toll-Like Receptor 2/4 (TLR2/4) and the Receptor for Advanced Glycation End Products (RAGE), thereby triggering systemic inflamma-tion and neuroinflammation that disrupts Blood-Brain Barrier (BBB) integrity, promotes microglial activation, and induces synaptic dysfunction, ultimately leading to cognitive impairment. This article reviews recent studies on the role of HMGB1 in MIRI and cognitive dysfunction and aims to elucidate its potential interplay with the recently identified adipokine, Meteorin-like (Metrnl), which has also been shown to be critically involved in both MIRI and cognition; subsequently, the HMGB1/Metrnl functional antagonism may be a potential therapeutic mechanism for MIRI-induced cognitive impairment. Addressing the HMGB1/Metrnl interplay offers a pathway to mitigate the long-term disability and loss of independence associated with MIRI-induced cognitive impairment, potentially alleviating the substantial socioeconomic burden and caregiver strain that follows major cardiac events.
