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Updated: Jan 2, 2026
Improved Rodent Model of Myocardial Ischemia and Reperfusion Injury
Published on: March 7, 2022
Ginsenoside Rg3-loaded, reactive oxygen species-responsive polymeric nanoparticles for alleviating myocardial
1First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China; Tianjin Key Laboratory of Translational Research of TCM Prescription and Syndrome, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.
Abstract:
Myocardial ischemia-reperfusion injury (MIRI) is a serious threat to the health and lives of patients without any effective therapy. Excessive production of reactive oxygen species (ROS) is considered a principal cause of MIRI. Some natural products, including ginsenoside Rg3 (Rg3), exhibit robust antioxidant activity. However, the lack of an effective delivery strategy for this hydrophobic compound hinders its clinical application. In addition, therapeutic targets and molecular mechanisms of Rg3 require further elucidation to establish its mode of action. This study aimed to generate ROS-responsive nanoparticles (PEG-b-PPS) via the self-assembly of diblock copolymers of poly (ethylene glycol) (PEG) and poly (propylene sulfide) (PPS) and use them for Rg3 encapsulation and delivery. We identified FoxO3a as the therapeutic target of Rg3 using molecular docking and gene silencing. In rat ischemia-reperfusion model, an intramyocardial injection of Rg3-loaded PEG-b-PPS nanoparticles improved the cardiac function and reduced the infarct size. The mechanism of action was established as Rg3 targeting of FoxO3a, which inhibited the promotion of oxidative stress, inflammation, and fibrosis via downstream signaling pathways. In conclusion, this approach, involving ROS-responsive drug release, together with the identification of the target and mechanism of action of Rg3, provided an effective strategy for treating ischemic diseases and oxidative stress and could accelerate the implementation of hydrophobic natural products in clinical applications.
Insights
Ginsenoside Rg3 delivered via ROS-responsive nanoparticles effectively treats myocardial ischemia-reperfusion injury by targeting FoxO3a, reducing oxidative stress and improving cardiac function.
Area of Science:
- Biomedical Engineering
- Cardiovascular Research
- Pharmacology
Background:
- Myocardial ischemia-reperfusion injury (MIRI) lacks effective therapies, with excessive reactive oxygen species (ROS) production as a key cause.
- Ginsenoside Rg3 (Rg3), a natural product, shows antioxidant potential but faces delivery challenges due to its hydrophobicity.
- Understanding Rg3's therapeutic targets and mechanisms is crucial for its clinical application.
Purpose of the Study:
- To develop ROS-responsive nanoparticles (PEG-b-PPS) for Rg3 delivery.
- To identify the molecular target and elucidate the mechanism of action of Rg3 in MIRI.
- To evaluate the therapeutic efficacy of Rg3-loaded nanoparticles in a rat MIRI model.
Main Methods:
- Self-assembly of poly (ethylene glycol)-poly (propylene sulfide) (PEG-b-PPS) diblock copolymers to create ROS-responsive nanoparticles.
- Molecular docking and gene silencing to identify Rg3's therapeutic target (FoxO3a).
- Intramyocardial injection of Rg3-loaded nanoparticles in a rat MIRI model to assess cardiac function and infarct size.
Main Results:
- Rg3-loaded PEG-b-PPS nanoparticles were successfully generated for hydrophobic drug delivery.
- FoxO3a was identified as the direct therapeutic target of Rg3.
- Treatment with Rg3-loaded nanoparticles significantly improved cardiac function and reduced infarct size in rats.
Conclusions:
- The study presents an effective strategy for MIRI treatment using ROS-responsive Rg3 delivery targeting FoxO3a.
- This approach mitigates oxidative stress, inflammation, and fibrosis, offering a promising therapeutic avenue.
- The findings facilitate the clinical translation of hydrophobic natural products like Rg3 for ischemic diseases.
