Published online Jul 15, 2023. doi: 10.4239/wjd.v14.i7.1057
Peer-review started: January 20, 2023
First decision: April 11, 2023
Revised: April 14, 2023
Accepted: May 5, 2023
Article in press: May 5, 2023
Published online: July 15, 2023
Processing time: 173 Days and 20.8 Hours
Patients with diabetes mellitus are at higher risk of myocardial ischemia/ reperfusion injury (MI/RI). Shuxin decoction (SXT) is a proven recipe modi-fication from the classic herbal formula "Wu-tou-chi-shi-zhi-wan" according to the traditional Chinese medicine theory. It has been successfully used to alleviate secondary MI/RI in patients with diabetes mellitus in the clinical setting. However, the underlying mechanism is still unclear.
To further determine the mechanism of SXT in attenuating MI/RI associated with diabetes.
This paper presents an ensemble model combining network pharmacology and biology. The Traditional Chinese Medicine System Pharmacology Database was accessed to select key components and potential targets of the SXT. In parallel, therapeutic targets associated with MI/RI in patients with diabetes were screened from various databases including Gene Expression Omnibus, DisGeNet, Genecards, Drugbank, OMIM, and PharmGKB. The potential targets of SXT and the therapeutic targets related to MI/RI in patients with diabetes were intersected and subjected to bioinformatics analysis using the Database for Annotation, Visualization and Integrated Discovery. The major results of bioinformatics analysis were subsequently validated by animal experiments.
According to the hypothesis derived from bioinformatics analysis, SXT could possibly ameliorate lipid metabolism disorders and exert anti-apoptotic effects in MI/RI associated with diabetes by reducing oxidized low density lipoprotein (LDL) and inhibiting the advanced glycation end products (AGE)-receptor for AGE (RAGE) signaling pathway. Subsequent animal experiments confirmed the hypothesis. The treatment with a dose of SXT (2.8 g/kg/d) resulted in a reduction in oxidized LDL, AGEs, and RAGE, and regulated the level of blood lipids. Besides, the expression of apoptosis-related proteins such as Bax and cleaved caspase 3 was down-regulated, whereas Bcl-2 expression was up-regulated. The findings indicated that SXT could inhibit myocardial apoptosis and improve cardiac function in MI/RI in diabetic rats.
This study indicated the active components and underlying molecular therapeutic mechanisms of SXT in MI/RI with diabetes. Moreover, animal experiments verified that SXT could regulate the level of blood lipids, alleviate cardiomyocyte apoptosis, and improve cardiac function through the AGE-RAGE signaling pathway.
Core Tip: Patients with diabetes are susceptible to myocardial ischemia/reperfusion injury (MI/RI). The efficacy of implementing strict glycemic control to reduce cardiovascular mortality in patients with diabetes has not been established to yield significant benefits. Here, we evaluated a recipe [Shuxin decoction (SXT)], which was modified from the classic herbal formula "Wu-tou-chi-shi-zhi-wan" in traditional Chinese medicine. Animal experiments based on findings from network pharmacology indicated that SXT could regulate lipid metabolism, alleviate cardiomyocyte apoptosis, and attenuate MI/RI in diabetes through the advanced glycation end products (AGE)-receptor for AGE signaling pathway. These findings could potentially facilitate developing a novel complementary or alternative form of medicine for effectively managing MI/RI with diabetes.