Frontiers in pharmacology · 2026
Proteomic results indicate inhibition of complement cascades is one of the mechanisms underlying the protective effects of Tongxinluo against myocardial infarction.
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Zhou Ziqin, Zhang Ce, Jiang Yao, Yang Yuejin, Chen Guihao, Pan Qi, Chen Jimei
Аннотация
OBJECTIVE: Tongxinluo (TXL), a traditional Chinese medicine, has demonstrated cardioprotective effects in acute myocardial infarction (AMI), yet its impact on myocardial protein profiles remains largely unexplored. This study aimed to elucidate the proteomic mechanisms underlying the therapeutic effects of TXL in AMI.
METHODS: AMI was induced via left anterior descending artery ligation in C57BL/6J mice. TXL was administered by oral gavage during the acute phase. Myocardial tissues and serum were subjected to 4D label-free quantitative proteomics, Western blotting, ELISA, immunofluorescence, TUNEL staining, and molecular docking analyses. Cardiac function was evaluated by echocardiography and fibrosis was quantified by Sirius red staining.
RESULTS: Proteomic analysis identified 1,061 differentially expressed proteins between TXL- and vehicle-treated AMI mice, with KEGG enrichment highlighting significant downregulation of complement and coagulation cascades. Key complement components C1qa and C1s were markedly upregulated post-AMI but significantly suppressed by TXL. Molecular docking suggested potential interactions between multiple TXL bioactive compounds and C1qa/C1s. TXL treatment reduced complement activation (serum C3a), inhibited cardiomyocyte apoptosis (Bax/Bcl-2, TUNEL), improved left ventricular ejection fraction, and attenuated fibrosis. Notably, TXL monotherapy outperformed C1 inhibitor (C1i) alone, while combining C1i with TXL conferred no additional benefit, indicating that C1 complement inhibition is an intrinsic component of TXL's mechanism.
CONCLUSION: Modulation of C1-associated complement activation may be one of the mechanisms through which TXL protects against AMI, providing novel proteomic-level insights into the cardioprotective actions of this traditional Chinese medicine.
METHODS: AMI was induced via left anterior descending artery ligation in C57BL/6J mice. TXL was administered by oral gavage during the acute phase. Myocardial tissues and serum were subjected to 4D label-free quantitative proteomics, Western blotting, ELISA, immunofluorescence, TUNEL staining, and molecular docking analyses. Cardiac function was evaluated by echocardiography and fibrosis was quantified by Sirius red staining.
RESULTS: Proteomic analysis identified 1,061 differentially expressed proteins between TXL- and vehicle-treated AMI mice, with KEGG enrichment highlighting significant downregulation of complement and coagulation cascades. Key complement components C1qa and C1s were markedly upregulated post-AMI but significantly suppressed by TXL. Molecular docking suggested potential interactions between multiple TXL bioactive compounds and C1qa/C1s. TXL treatment reduced complement activation (serum C3a), inhibited cardiomyocyte apoptosis (Bax/Bcl-2, TUNEL), improved left ventricular ejection fraction, and attenuated fibrosis. Notably, TXL monotherapy outperformed C1 inhibitor (C1i) alone, while combining C1i with TXL conferred no additional benefit, indicating that C1 complement inhibition is an intrinsic component of TXL's mechanism.
CONCLUSION: Modulation of C1-associated complement activation may be one of the mechanisms through which TXL protects against AMI, providing novel proteomic-level insights into the cardioprotective actions of this traditional Chinese medicine.