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Tanyu Tongzhi Decoction Improves Cardiac Function by Inhibiting Platelet Activation and Alleviating Coronary
Ying Yang1, Xiang Li1, Danli Tang2
1Institute of Basic Theory for Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China.
Insights
Tanyu Tongzhi Decoction (TYTZD) effectively treats coronary heart disease (CHD) with syndrome of intermingled phlegm and blood stasis (SI-GPBS) by inhibiting platelet activation and improving endothelial function. This study elucidates its mechanism, supporting clinical use.
Area of Science:
- Cardiovascular Research
- Traditional Chinese Medicine
- Proteomics
Background:
- Coronary heart disease (CHD) presents a significant global health challenge.
- The syndrome of intermingled phlegm and blood stasis (SI-GPBS) is a key traditional Chinese medicine diagnosis for CHD.
- Tanyu Tongzhi Decoction (TYTZD) shows cardioprotective effects, but its mechanism in SI-GPBS requires elucidation.
Purpose of the Study:
- To investigate the molecular mechanisms of TYTZD in treating CHD with SI-GPBS.
- To identify key molecular targets and pathways regulated by TYTZD.
- To provide an experimental basis for the clinical application of TYTZD.
Main Methods:
- Combined clinical serum proteomics, network pharmacology, and transcriptomics in an APOE-/- mouse model.
- Utilized Western blotting, immunofluorescence, and Carstairs staining for target validation.
- Assessed cardiac function, lipid profiles, and pathological changes.
Main Results:
- Identified 754 differentially expressed proteins in SI-GPBS, highlighting platelet activation pathways and ITGA2B as a hub protein.
- Network pharmacology revealed 94 active ingredients and 144 targets for TYTZD, with key components interacting with ITGA2B.
- TYTZD treatment in mice reduced cardiac damage, lipid deposition, and coronary microthrombosis, downregulating key proteins and inhibiting integrin αIIbβ3 signaling.
Conclusions:
- TYTZD primarily treats CHD with SI-GPBS by inhibiting platelet activation and improving endothelial dysfunction.
- The study demonstrates TYTZD's efficacy in reducing coronary microthrombosis.
- Findings support TYTZD's clinical use and offer insights into TCM syndrome-disease research.
Abstract:
Background: Coronary heart disease (CHD) has a high global disease burden. According to traditional Chinese medicine theory, the main syndrome type of CHD is the syndrome of intermingled phlegm and blood stasis (SI-GPBS). Tanyu Tongzhi Decoction (TYTZD) exerts clear cardioprotective effects on CHD patients with SI-GPBS, while its specific regulatory mechanism remains unclear. Methods: Clinical serum proteomics and network pharmacology were used to screen key targets and pathways for CHD with SI-GPBS. An APOE-/- mouse model of CHD complicated with SI-GPBS was established and treated with TYTZD. Transcriptomics, proteomics and WGCNA were combined to screen core genes, with Western blotting, immunofluorescence, co-localization analysis and Carstairs staining for target verification and observation of coronary microthrombosis and endothelial injury. Results: A total of 754 differentially expressed proteins were identified in CHD patients with SI-GPBS, significantly enriched in the platelet activation pathway, with ITGA2B as the upregulated core hub protein. Network pharmacology found 94 active ingredients and 144 therapeutic targets of TYTZD for CHD with SI-GPBS, and key components bound well with ITGA2B. In APOE-/- mice with SI-GPBS, TYTZD improved cardiac function, reduced blood lipids, myocardial enzymes, aortic lipid deposition and myocardial damage, downregulated ITGA2B, F2RL2, FGA and FGB, inhibited integrin αIIbβ3 signaling, restrained endothelial activation and reduced coronary microthrombosis. Conclusions: TYTZD treats CHD with SI-GPBS mainly by inhibiting platelet activation, improving endothelial dysfunction, and reducing coronary microthrombosis. This study provides experimental basis for TYTZD's clinical application in CHD with SI-GPBS and new ideas for TCM syndrome-disease combination research.