# Gastrodin reduces myocardial ischemia/reperfusion injury via transgelin2/CNPase-mediated apoptosis regulation

## TL;DR

Gastrodin protects heart tissue during reperfusion injury by regulating a protein pathway that reduces cell death.

## Contribution

Gastrodin's protective effect in MIRI is revealed to involve the TG2/CNPase pathway, offering a novel therapeutic mechanism.

## Key findings

- Gastrodin reduces myocardial infarction size and cardiac dysfunction in rats.
- TG2 binds and regulates CNPase, and their imbalance promotes apoptosis in MIRI.
- Gastrodin restores TG2/CNPase balance, thereby inhibiting cardiomyocyte apoptosis.

## Abstract

Myocardial ischemia-reperfusion injury (MIRI) frequently occurs during rapid restoration of blood flow in the infarcted myocardium. While Gastrodin (GAS) mitigates MIRI, its mechanism requires further exploration.

We evaluated GAS effect in SD rats following 45-min left coronary artery ligation and reperfusion. GAS (intraperitoneal) was administered preoperatively for 3 days. Triphenyltetrazolium chloride (TTC) staining was used to detect infarct size. The cardiac function was monitored by the Langendorff isolated cardiac perfusion system. Hematoxylin-Eosin (H&E) staining was applied to detect cardiac injury. H9c2 cells underwent oxygen and glucose deprivation (OGD) and were subsequently restored to normal culture conditions, mimicking MIRI. Cell Counting Kit-8 (CCK-8) was used to detect the cytotoxicity of GAS. Myocardial cell injury was determined by detecting lactate dehydrogenase (LDH) level in the medium. The expression of protein was detected by Western blot (WB) and immunofluorescence (IF) assay. Coimmunocoprecipitation (Co-IP), coupled with molecular docking detected the combination among transgelin2 (TG2), and CNPase.

GAS reduced the size of myocardial infarction, alleviated myocardial fiber damage, and ameliorated MIRI-mediated cardiac dysfunction. Mechanistically, GAS inhibited apoptosis by restoring MIRI-altered TG2/CNPase expression. TG2 directly bound and negatively regulated CNPase. CNPase deficiency enhanced MIRI amelioration by reducing apoptosis.

Taken together, GAS protects against MIRI by modulating apoptosis through the TG2/CNPase pathway, revealing a novel therapeutic target.

Gastrodin alleviates MIRI by suppressing TG2/CNPase-mediated apoptosis. In MIRI, reduced TG2 expression in cardiomyocytes leads to elevated CNPase levels due to disrupted TG2-CNPase binding and regulatory control. This imbalance promotes cardiomyocyte apoptosis. GAS administration counteracts this pathway by enhancing TG2 expression, thereby normalizing CNPase levels and attenuating apoptotic signaling.Diagram showing the process of myocardial ischemia-reperfusion injury (MIRI) in rats. GAS reduces MIRI, reducing CNPase and TG2. CNPase expression is linked to increased Bax, decreased Bcl-2, and increased c-Caspase3, leading to apoptosis. The diagram illustrates the pathway with arrows indicating the relationships between components. Rats are depicted with a heart and syringe.

Gastrodin alleviates MIRI by suppressing TG2/CNPase-mediated apoptosis. In MIRI, reduced TG2 expression in cardiomyocytes leads to elevated CNPase levels due to disrupted TG2-CNPase binding and regulatory control. This imbalance promotes cardiomyocyte apoptosis. GAS administration counteracts this pathway by enhancing TG2 expression, thereby normalizing CNPase levels and attenuating apoptotic signaling.