Emodin ameliorates myocardial fibrosis in mice by inactivating the ROS/PI3K/Akt/mTOR axis

ABSTRACT

Background

Emodin is a traditional medicine that has been shown to exert anti-inflammatory and anti-oxidative effects. Previous research has indicated that emodin can alleviate myocardial remodeling and inhibit myocardial hypertrophy and fibrosis. However, the mechanism by which emodin affects myocardial fibrosis (MF) has not yet been elucidated.

Methods

Fibroblasts were treated with ANGII, and a mouse model of MF was established by ligation of the left anterior descending coronary artery. Cell proliferation was examined by a Cell Counting Kit-8 (CCK8) assay. Dihydroethidium (DHE) was used to measure reactive oxygen species (ROS) levels, and Masson and Sirius red staining were used to examine changes in collagen fiber levels. PI3K was over-expressed by lentiviral transfection to verify the effect of emodin on the PI3K/AKT/mTOR signaling axis. Changes in cardiac function in each group were examined by echocardiography.

Results

Emodin significantly inhibited fibroblast proliferation, decreased intracellular ROS levels, significantly upregulated collagen II expression, downregulated α-SMA expression, and inhibited PI3K/AKT/mTOR pathway activation in vitro. Moreover, the in vivo results were consistent with the in vitro. Emodin significantly decreased ROS levels in heart tissue and reduced collagen fibrillogenesis. Emodin could regulate the activity of PI3K to increase the expression of collagen II and downregulate α-SMA expression in part through the PI3K/AKT/mTOR pathway, and emodin significantly improved cardiac structure and function in mice.

Conclusions

This study revealed that emodin targeted the PI3K/AKT/mTOR pathway to inhibit the development of myocardial fibrosis and may be an antifibrotic agent for the treatment of cardiac fibrosis.

KEYWORDS:

• Emodin
• myocardial fibrosis
• reactive oxygen species
• collagen synthesis
• PI3K/AKT/mTOR axis

Acknowledgments

We thank Xiang-yun Wu for assistance establishing the MF model.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contributions

All the authors made significant contributions to the work reported, whether in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas. All the authors took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; agreed on the journal to which the article was submitted; and agreed to be accountable for all aspects of the work.

Data availability statement

The data presented in this study are available upon request from the corresponding author.

Ethics approval and consent to participate

All animal treatments were approved (approval no. 2020-ky75) by the Laboratory Animal Welfare and Ethics Committee of the General Hospital of Western Theater Command (Chengdu, China).

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/10641963.2024.2326022

Additional information

Funding

This work was supported by Key Research and Development Projects of the Sichuan Provincial Department of Science and Technology [2019YFS0198], Hospital Management Research of Western Theater General Hospital [2021-XZYG-C16], and the Sichuan Natural Science Foundation General Project [2022NSFSC0738].