Exploring the protective effects of PNS on acute myocardial ischaemia-induced heart failure by Transcriptome analysis

Ethnopharmacological relevance: Panax notoginseng saponins (PNS) were extracted from Panax notoginseng (Burkill) F.H. Chen, a natural product often used as a therapeutic agent in China. PNS has showed obvious therapeutic effect in heart failure (HF) treatment. However, its targets and pharmacological mechanisms remain elusive. Aim of the study: This research attempted to determine both the effects and mechanisms of PNS involved in AMI treatment, namely, acute myocardial infarction-induced HF. Materials and methods: An AMI-induced HF model was generated by left anterior descending (LAD) ligation in rats. Transcriptome analyses were performed to identify differentially expressed genes (DEGs) and pathway enrichment. Real-time quantitative PCR (RT-qPCR) verified the HF-related genes differentially expressed after PNS treatment. Finally, a model of H9C2 cells subjected to OGD/R, which is equivalent to oxygen-glucose deprivation/reperfusion, was established to identify the potential mechanism of PNS in the treatment of HF. Results: PNS ameliorated cardiac function and protected against structural alterations of the myocardium in HF rats. Transcriptome analysis showed that PNS upregulated 1749 genes and downregulated 1069 genes in the heart. Functional enrichment analysis demonstrated that the metabolic process was enriched among the DEGs. KEGG pathway analysis revealed that the PPAR signalling pathway was particularly involved in the protective function of PNS. The effects of PNS on the PPAR pathway were validated in vivo; PNS treatment effectively increased the expression of PPAR alpha, RXR alpha, and PGC1 alpha in rats with AMI-induced HF. In addition, PNS was shown to regulate the expression of downstream energy metabolism-related proteins. Interestingly, the addition of the PPAR alpha inhibitor GW6471 abolished the beneficial effects of PNS. Conclusions: PNS exerts a cardioprotective function in a multicomponent and multitarget manner. The PPAR signalling pathway is one of the key pathways by which PNS protects against HF, and PPAR alpha is a possible target for HF treatment.

Automated summary

The study confirmed the cardioprotective effects of PNS and its involvement in metabolic processes through the PPAR signaling pathway in HF treatment. PNS was found to upregulate genes, particularly those related to energy metabolism, and the PPAR alpha pathway was identified as a key mechanism for the protective function of PNS. The inhibition of PPAR alpha abolished the beneficial effects of PNS, suggesting that PPAR alpha may be a potential target for HF treatment.