ArticlePharmacological research2016
Higenamine protects ischemia/reperfusion induced cardiac injury and myocyte apoptosis through activation of β2-AR/PI3K/AKT signaling pathway.
Article in Pharmacological research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 82 citations in OpenAlex.
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- Higenamine Hydrochloride Ameliorates Diabetic Cardiomyopathy Through RhoA/MEK/ERK Pathway.Inflammation · 2025Article
- Systematic understanding of mechanism of Shenfu decoction improve the prognosis of ischemic stroke using a network pharmacology and animal experiment approach.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2025Article
- Therapeutic potential and mechanisms of traditional Chinese medicine in regulating energy metabolism imbalance in heart failure.Chinese herbal medicines · 2025Review
- Temporal Dynamics of Extracellular Matrix Remodeling in Anthracycline-Induced Cardiotoxicity.Cells · 2025Review
- A Narrative Review on Higenamine: Pharmacological Properties and Clinical Applications.Nutrients · 2025Review
- Hypoxia Regulates the Proliferation and Apoptosis of Coronary Artery Smooth Muscle Cells Through HIF-1α Mediated Autophagy in Yak.Biomolecules · 2025Article
- Demonstration of the Protective Effect of Vinpocetine in Diabetic Cardiomyopathy.Journal of clinical medicine · 2024Article
- Liraglutide Attenuates Diabetic Cardiomyopathy via the ILK/PI3K/AKT/PTEN Signaling Pathway in Rats with Streptozotocin-Induced Type 2 Diabetes Mellitus.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Cardiovascular protection of YiyiFuzi powder and the potential mechanisms through modulating mitochondria-endoplasmic reticulum interactions.Frontiers in pharmacology · 2024Review
- Role of cAMP in Cardiomyocyte Viability: Beneficial or Detrimental?Circulation research · 2023Article
- Network pharmacology and molecular docking to explore Polygoni Cuspidati Rhizoma et Radix treatment for acute lung injury.World journal of clinical cases · 2023Article
- Research Progress on Neuroprotective Effects of Isoquinoline Alkaloids.Molecules (Basel, Switzerland) · 2023Review
- Natural Products Targeting PI3K/AKT in Myocardial Ischemic Reperfusion Injury: A Scoping Review.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Fuziline Ameliorates Glucose and Lipid Metabolism by Activating Beta Adrenergic Receptors to Stimulate Thermogenesis.International journal of molecular sciences · 2023Article
- The traditional Chinese medicines treat chronic heart failure and their main bioactive constituents and mechanisms.Acta pharmaceutica Sinica. B · 2023Review
- Exploration of Habitat-Related Chemical Markers forMolecules (Basel, Switzerland) · 2022Article
- Suppressive effects of processed aconite root on dexamethasone-induced muscle ring finger protein-1 expression and its active ingredients.Journal of natural medicines · 2022Article
- Processed lateral root ofFrontiers in pharmacology · 2022Review
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Cardiomyocyte apoptosis contributes to ischemic cardiac injury and the development of heart failure. Higenamine is a key component of the Chinese herb aconite root that has been prescribed for treating symptoms of heart failure for thousands of years in the oriental Asian countries. It has been shown that higenamine has anti-apoptotic effects in a few cell types including cardiomyocytes. However, the pharmacological target and molecular mechanism of higenamine in the heart are still not fully illustrated. Herein, we report that higenamine protected myocyte apoptosis and ischemia/reperfusion (I/R) injury through selective activation of beta2-adrenergic receptor (β2-AR). In particular, we show that higenamine significantly reduced I/R-induced myocardial infarction in mice. In both primary neonatal rat and adult mouse ventricular myocytes, we show higenamine inhibited cell apoptosis and also reduced biochemical markers of apoptosis such as cleaved caspase 3 and 9. More importantly, we show that the anti-apoptotic effects of higenamine in cardiomyocytes were completely abolished by β2-AR but not β1-AR antagonism. Furthermore, we confirmed that higenamine attenuated I/R-induced myocardial injury and reduced cleaved caspases in a β2-AR dependent manner in intact mouse hearts. Higenamine stimulated AKT phosphorylation and required PI3K activation for the anti-apoptotic effect in cardiomyocytes. These findings together suggest that anti-apoptotic and cardiac protective effects of higenamine are mediated by the β2-AR/PI3K/AKT cascade.
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