Taohong Siwu decoction reduces acute myocardial ischemia-reperfusion injury by promoting autophagy to inhibit pyroptosis

Abstract

Ethnopharmacological relevance: Taohong Siwu decoction (TSD) is a classic traditional Chinese medicine (TCM) prescription used to promote the blood circulation and alleviate blood stasis. TSD consists of Paeonia lactiflora Pall., Conioselinum anthriscoides (H. Boissieu) Pimenov & Kljuykov, Rehmannia glutinosa (Gaertn.) DC., Prunus persica (L.) Batsch, Angelica sinensis (Oliv.) Diels, and Carthamus creticus L. in the ratio of 3:2:4:3:3:2. Studies on the effects of TSD on myocardial ischemia-reperfusion injury (MIRI) from the perspective of autophagy and pyroptosis have not been reported.

Aim of the study: Investigate the effect of TSD on MIRI and explore the underlying mechanisms.

Materials and methods: We searched the main components and corresponding potential targets of TSD on The Pharmacology of Traditional Chinese Medicine Systems database for target prediction. We identified targets for MIRI on Online Mendelian Inheritance in Man and GeneCards databases. The intersection of the compound target and disease target was obtained and a protein-protein interaction network constructed. We undertook enrichment analyses using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases. The results of network pharmacology were verified by in vivo experiments in mice.

Results: In mice, TSD significantly reduced the volume of the myocardial infarct, significantly reduced serum levels of cardiac troponin-nI (CTnI), creatine kinase-myocardial band (CK-MB), malonaldehyde (MDA), interleukin (IL)-6, increased the activity of superoxide dismutase (SOD) and IL-10 level, reduced the level of pyroptosis in myocardial tissue, increased the number of autophagosomes, and significantly reduced the fluorescence intensity of apoptosis-associated speck-like protein (ASC), Nod-like receptor protein 3 (NLRP3), and caspase-1. TSD administration increased the protein expression of microtubule-associated protein light chain 3 (LC3), but reduced the protein expression of p62, NLRP3, ASC, caspase-1, cleaved caspase-1, pro-caspase-1, gasdermin D (GSDMD), GSDMD-N-terminal, IL-18, and IL-1β. Administration of 3-Methyladenin could reverse the effect of TSD in inhibiting inflammation and the release of proinflammatory factors.

Conclusion: TSD treatment alleviated MIRI by promoting autophagy to suppress activation of the NLRP3 inflammasome and reducing the release of proinflammatory factors.

Keywords: Autophagy; Myocardial ischemia–reperfusion injury; NLRP3 inflammasome; Pyroptosis; Taohong Siwu decoction.