Gastrodin Alleviates Angiotensin II-Induced Hypertension and Myocardial Apoptosis via Inhibition of the PRDX2/p53 Pathway In Vivo and In Vitro

Gastrodin, a highly potent compound found in the traditional Chinese medicine <i>Gastrodia elata</i> Blume, exhibits significant antihypertensive properties. However, its role and the mechanism behind its protective effects on hypertensive cardiac conditions are not well understood. This study aims to investigate the cardiac protective effects and underlying mechanisms of gastrodin in angiotensin II (Ang II)-induced hypertensive models, both in vivo and in vitro. Treatment with gastrodin significantly decreased blood pressure and the heart weight/tibial length (HW/TL) ratio and attenuated cardiac dysfunction and pathological damage in Ang II-infused C57BL/6 mice. RNA sequencing analysis (RNA-seq) revealed 697 up-regulated and 714 down-regulated transcripts, along with 1105 signaling pathways, in Ang II-infused C57BL/6 mice following gastrodin treatment, compared to Ang II-induced hypertensive mice. Furthermore, the analyses of the top 30 Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway indicated significant enrichment in apoptosis and the peroxiredoxin 2 (PRDX2)/p53 pathway. Consistently, gastrodin treatment significantly reduced myocardial apoptosis in both the cardiac tissues of Ang II-induced hypertensive mice and Ang II-stimulated H9c2 cells. Additionally, gastrodin treatment significantly decreased the protein levels of PRDX2, p53, cleaved caspase-3, cleaved caspase-9, and Bax/Bcl-2 ratio in the cardiac tissues of Ang II-infused mice and H9c2 cells stimulated with Ang II. In conclusion, gastrodin treatment can mitigate hypertension-induced myocardial apoptosis in hypertensive mice by inhibiting the PRDX2/p53 pathway.