PUBLICATION

Qiangxinyin formula protects against isoproterenol-induced cardiac hypertrophy

Authors
Zhou, Z.Y., Ma, J., Zhao, W.R., Shi, W.T., Zhang, J., Hu, Y.Y., Yue, M.Y., Zhou, W.L., Yan, H., Tang, J.Y., Wang, Y.
ID
ZDB-PUB-240530-6
Date
2024
Source
Phytomedicine : international journal of phytotherapy and phytopharmacology   130: 155717155717 (Journal)
Registered Authors
Keywords
Calcium overload, Cardiac fibrosis, Cardiac hypertrophy, Heart failure, Traditional Chinese medicine, Zebrafish
MeSH Terms
  • Drugs, Chinese Herbal*/pharmacology
  • Rats
  • Calcium/metabolism
  • Cardiotonic Agents/pharmacology
  • Myocytes, Cardiac*/drug effects
  • Zebrafish*
  • Cardiomegaly*/chemically induced
  • Cardiomegaly*/drug therapy
  • Cardiomegaly*/prevention & control
  • Animals
  • Cell Line
  • Isoproterenol*
  • Membrane Potential, Mitochondrial/drug effects
PubMed
38810550 Full text @ Phytomedicine
Abstract
Heart failure is a life-threatening cardiovascular disease and characterized by cardiac hypertrophy, inflammation and fibrosis. The traditional Chinese medicine formula Qiangxinyin (QXY) is effective for the treatment of heart failure while the underlying mechanism is not clear. This study aims to identify the active ingredients of QXY and explore its mechanisms protecting against cardiac hypertrophy. We found that QXY significantly protected against isoproterenol (ISO)-induced cardiac hypertrophy and dysfunction in zebrafish. Eight compounds, including benzoylmesaconine (BMA), atractylenolide I (ATL I), icariin (ICA), quercitrin (QUE), psoralen (PRN), kaempferol (KMP), ferulic acid (FA) and protocatechuic acid (PCA) were identified from QXY. PRN, KMP and icaritin (ICT), an active pharmaceutical ingredient of ICA, prevented ISO-induced cardiac hypertrophy and dysfunction in zebrafish. In H9c2 cardiomyocyte treated with ISO, QXY significantly blocked the calcium influx, reduced intracellular lipid peroxidative product MDA, stimulated ATP production and increased mitochondrial membrane potential. QXY also inhibited ISO-induced cardiomyocyte hypertrophy and cytoskeleton reorganization. Mechanistically, QXY enhanced the phosphorylation of Smad family member 2 (SMAD2) and myosin phosphatase target subunit-1 (MYPT1), and suppressed the phosphorylation of myosin light chain (MLC). In conclusion, PRN, KMP and ICA are the main active ingredients of QXY that protect against ISO-induced cardiac hypertrophy and dysfunction largely via the blockage of calcium influx and inhibition of mitochondrial dysfunction as well as cytoskeleton reorganization.
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