Stachydrine hydrochloride suppresses phenylephrine-induced pathological cardiac hypertrophy by inhibiting the calcineurin/nuclear factor of activated T-cell signalling pathway.

Abstract

The calcineurin (CaN)/nuclear factor of activated T-cell (NFAT) signalling pathway plays an important role in pathological cardiac hypertrophy. Here, we investigated the potential effects of stachydrine hydrochloride, a bioactive constituent extracted from the Chinese herb Leonurus japonicus Houtt. (Yimucao), on pathological cardiac hypertrophy during chronic α1-adrenergic receptor (α1-AR) activation and the underlying mechanisms. First, by transcriptome analysis, we determined that pathological hypertrophy models could be prepared after phenylephrine stimulation. In primary cultured neonatal rat ventricular myocytes, stachydrine hydrochloride reduced phenylephrine-induced cardiomyocyte surface area and the mRNA expression of cardiac hypertrophy biomarkers (atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), and β-myosin heavy chain/α-myosin heavy chain (β-MHC/α-MHC)). In addition, phenylephrine stimulation potently induced activation of the CaN/NFAT pathway. Interestingly, stachydrine hydrochloride inhibited CaN activation and reduced NFATc3 nuclear translocation in phenylephrine-stimulated neonatal rat ventricular myocytes. In mice treated with phenylephrine, stachydrine hydrochloride treatment decreased cardiac hypertrophy and regulated heart function. Collectively, our data show that stachydrine hydrochloride decreases cardiac hypertrophy in phenylephrine-stimulated hearts by inhibiting the CaN/NFAT pathway, which might contribute to alleviation of pathological cardiac hypertrophy and cardiac dysfunction by stachydrine hydrochloride after phenylephrine stimulation This also indicated that governing of CaN/NFAT pathway might serve as a preventive or therapeutic strategy for pathological cardiac hypertrophy.

• Authors: Jiali Zheng, Jing Tian, Sining Wang, Panwei Hu, Qianfu Wu, Xiaoli Shan, Pei Zhao, Chen Zhang, Wei Guo, Ming Xu, Huihua Chen, Rong Lu
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 883 Pg. 173386 (Sep 15 2020) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 32712088 (Publication Type: Journal Article)
• Copyright: Copyright © 2020. Published by Elsevier B.V.

Chemical References

• NFATC Transcription Factors
• Phenylephrine
• Proline
• Calcineurin
• stachydrine

Topics

• Animals
• Calcineurin (metabolism)
• Cells, Cultured
• Disease Models, Animal
• Gene Expression Regulation
• Hypertrophy, Left Ventricular (chemically induced, enzymology, physiopathology, prevention & control)
• Mice, Inbred C57BL
• Myocytes, Cardiac (drug effects, enzymology, pathology)
• NFATC Transcription Factors (metabolism)
• Phenylephrine
• Proline (analogs & derivatives, pharmacology)
• Rats, Wistar
• Signal Transduction
• Ventricular Function, Left (drug effects)
• Ventricular Remodeling (drug effects)