JinLiDa granules alleviates cardiac hypertrophy and inflammation in diabetic cardiomyopathy by regulating TP53

Ting Fang; Jingyi Wang; Shengnan Sun; Xiaoqing Deng; Mei Xue; Fei Han; Bei Sun; Liming Chen

doi:10.1016/j.phymed.2024.155659

JinLiDa granules alleviates cardiac hypertrophy and inflammation in diabetic cardiomyopathy by regulating TP53

Phytomedicine. 2024 May 10:130:155659. doi: 10.1016/j.phymed.2024.155659. Online ahead of print.

Authors

Ting Fang¹, Jingyi Wang¹, Shengnan Sun¹, Xiaoqing Deng¹, Mei Xue², Fei Han¹, Bei Sun³, Liming Chen⁴

Affiliations

¹ NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300134, China.
² Department of Endocrinology, Zhongnan Hospital of Wuhan University, 430071 Wuhan, China.
³ NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300134, China. Electronic address: sun_peipei220@hotmail.com.
⁴ NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300134, China. Electronic address: xfx22081@vip.163.com.

PMID: 38759318
DOI: 10.1016/j.phymed.2024.155659

Abstract

Background: JinLiDa granules (JLD) is a traditional Chinese medicine (TCM) used to treat type 2 diabetes mellitus with Qi and Yin deficiency. Clinical evidence has shown that JLD can alleviate diabetic cardiomyopathy, but the exact mechanism is not yet clear.

Purpose: The purpose of this study was to examine the potential role and mechanism of JLD in the treatment of diabetic cardiomyopathy through network pharmacological analysis and basic experiments.

Methods: The targets of JLD associated with diabetic cardiomyopathy were examined by network pharmacology. Protein interaction analysis was performed on the targets, and the associated pathways were searched by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Diabetic mice were treated with low or high doses of JLD by gavage, and AC16 and H9C2 cardiomyocytes exposed to high-glucose conditions were treated with JLD. The analysis results were verified by various experimental techniques to examine molecular mechanisms.

Results: Network pharmacological analysis revealed that JLD acted on the tumor suppressor p53 (TP53) during inflammation and fibrosis associated with diabetic cardiomyopathy. The results of basic experiments showed that after JLD treatment, ventricular wall thickening in diabetic mouse hearts was attenuated, cardiac hypertrophy and myocardial inflammation were alleviated, and the expression of cardiac hypertrophy- and inflammation-related factors in cardiomyocytes exposed to a high-glucose environment was decreased. Cardiomyocyte morphology also improved after JLD treatment. TP53 expression and the tumor necrosis factor (TNF) and transforming growth factor beta-1 (TGFβ1) signaling pathways were significantly altered, and inhibiting TP53 expression effectively alleviated the activation of the TNF and TGFβ1 signaling pathways under high glucose conditions. Overexpression of TP53 activated these signaling pathways.

Conclusions: JLD acted on TP53 to regulate the TNF and TGFβ1 signaling pathways, effectively alleviating cardiomyocyte hypertrophy and inflammation in high glucose and diabetic conditions. Our study provides a solid foundation for the future treatment of diabetic cardiomyopathy with JLD.

Keywords: Diabetic cardiomyopathy; JinLiDa granules; Network pharmacology; TNF and TGFβ1 signaling pathway; Tumor suppressor p53.