# The treatment of myocardial ischemia-reperfusion injury: potential roles of natural drug modulating CaMKII

## TL;DR

This paper reviews how natural drugs may protect the heart from injury by targeting a key protein called CaMKII, offering new insights for treatment strategies.

## Contribution

The paper systematically reviews and evaluates natural drugs targeting CaMKII for myocardial ischemia-reperfusion injury using molecular docking and experimental validation.

## Key findings

- Natural drugs like alkaloids and flavonoids show potential in modulating CaMKII to reduce heart injury.
- Molecular docking confirmed strong binding affinity between selected natural compounds and CaMKII.
- Experimental models support the protective effects of these natural drugs in MIRI.

## Abstract

Myocardial ischemia-reperfusion injury (MIRI) represents a significant challenge in the treatment of cardiovascular diseases, with its complex pathogenesis involving multiple signaling pathways, such as calcium overload, oxidative stress, inflammatory responses, and cell apoptosis. Calcium/calm-odulin-dependent protein kinase II (CaMKII), a key calcium signaling transducer molecule, plays a central regulatory role in the onset and progression of MIRI. We conducted a comprehensive review of the literature on phytochemicals targeting CaMKII as a protective mechanism against MIRI. The search was performed across multiple databases, including PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), and Google Scholar, covering the period from January 2000 to September 2025. A total of 254 articles were retrieved, of which 16 were included in this review. Molecular docking was then performed to evaluate the binding affinity between natural drugs and CaMKII. This paper systematically summarizes the latest research findings on natural drugs that alleviate MIRI by targeting the CaMKII signaling pathway, with a particular focus on the mechanisms of action of representative natural drugs and their experimental validation in animal and cellular models. The aim is to provide a theoretical basis and research directions for the development and clinical application of natural drugs, thereby promoting innovation in prevention and treatment strategies for myocardial ischemia-reperfusion injury.

Diagram illustrating the effect of natural products on heart protection. Categories like alkaloid, flavonoid, glycoside, polyphenol, terpene, and TCM lead to CaM and CaMKII activation under pathological conditions. This results in myocardial protection, shown by a heart with a zoomed-in section of tissue.