Introduction

As the standard of living steadily improves, the aging population is on the rise, and myocardial infarction (MI) stands as the foremost contributor to both morbidity and mortality within the realm of cardiovascular diseases worldwide [1]. While modern reperfusion therapy serves as the most efficacious approach for diminishing infarct size and ameliorating clinical outcomes after MI, heart failure remains the primary cause of death subsequent to MI. The process of heart remodeling following MI is acknowledged as the initial phase leading toward heart failure [2, 3]. Consequently, the reversal of ventricular remodeling emerges as a highly desirable prospect for the treatment of MI. Certain angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), when administered as long-term treatment, have demonstrated the capacity to attenuate ventricular remodeling [4,5,6]. However, a significant number of patients encounter intolerance to ACEIs/ARBs due to conditions such as renal dysfunction, hypotension, or hyperkalemia, among others. Hence, there exists considerable interest in identifying novel therapeutic agents capable of enhancing ventricular remodeling, thereby addressing this pressing concern.

Myocardial fibrosis and ventricular remodeling have been identified as crucial pathological factors contributing to unfavorable outcomes following MI [7]. Of notable significance, the TGF‐β1/Smad signaling pathway exhibits a close association with both myocardial fibrosis and ventricular remodeling [8, 27,28,29]. TCM compounds are known to comprise a diverse array of Chinese medicinal ingredients that act through various targets, channels, and pathways to address diseases. Among these, icariin, the primary active ingredient derived from the Chinese herbal medicine Epimedium brevicornu Maxim, has garnered considerable interest [30, 31]. Several species of Epimedium can be used to extract it, including Epimedium sagitta, Epimedium pilose, Epimedium Wushan, and Epimedium korean. Icariin has been shown to protect the myocardium from ischemia and reperfusion in previous studies [32,33,34,35]. Icariin has a therapeutic effect on coronary heart disease, but its mechanism remains largely unclear. According to TCM principles, ventricular dysfunction and heart failure arise from Qi deficiency and blood stasis [36, 37]. In this study, icariin therapy exhibited notable improvements in LVEF and FS while concurrently reducing LVEDD and LVESD compared to the MI group. Moreover, this study sheds light on the hitherto unexplored function and mechanism of icariin in mitigating cardiac fibrosis.

The TGF-β1/Smad signaling pathway assumes a pivotal role in cardiac fibrosis and ventricular remodeling [38]. This study sought to quantify the changes in the expression levels of key molecules within the TGF-β1 signaling pathway. Notably, following MI, there was evident overexpression of TGF-β1 in the myocardium, whereas treatment with icariin resulted in a significant reduction in TGF-β1 in the ischemic myocardium. To validate this hypothesis, Western blotting was performed on M2-type macrophages induced by IL4, revealing that icariin supplementation led to decreased levels of TGF-β1 and Smad2/3. Presently, research concerning the antitumor activity of icariin has emerged as a prominent area of interest. These findings demonstrate that icariin effectively inhibits M2 macrophage polarization, signifying its potential to modulate the tumor microenvironment. Prior studies have already established icariin's ability to inhibit M2 macrophage polarization while promoting M1 macrophage polarization [18, 39]. There is still work to be done to determine whether icariin affects myocardial fibrosis and ventricular remodeling by regulating macrophage polarization.

In conclusion, the present study provides compelling evidence that icariin significantly reduces cardiac fibrosis and ameliorates cardiac function in rats with myocardial infarction. The potential protective effects of icariin are closely associated with modulation of the TGF-β1/Smad signaling pathway. However, it is essential to acknowledge certain limitations within this study. First, the follow-up period for the MI rats was relatively short, thereby precluding the observation of long-term changes in cardiac function. Second, given the intricate molecular mechanisms involved, the precise mechanisms through which icariin confers protective effects on cardiac fibrosis remain incompletely elucidated. Thus, further investigations are warranted to validate and expand upon the present findings.

Limitations of the study

Firstly, the selection of icariin dosage in our study was based on a review of pertinent literature. However, it is noteworthy that there is a dearth of dose–response investigations aimed at determining the most efficacious icariin dosage for achieving optimal outcomes. Additionally, comprehensive long-term safety evaluations for icariin treatment are presently lacking. Secondly, we did not employ TTC staining to validate the myocardial infarction's extent. Lastly, it should be acknowledged that this study was characterized by a limited sample size, an absence of power calculations, and the potential influence of uncontrolled confounding variables.

Conclusion

The findings of the current study suggest that icariin possesses the capacity to enhance cardiac function and mitigate ventricular remodeling in rats following MI. These results underscore icariin's potential as a viable therapeutic target for addressing myocardial injury and ventricular remodeling.