Abstract
Higenamine, a natural product with multiple targets in heart diseases, is originally derived from Aconitum, which has been traditionally used in China for the treatment of heart disease, including heart failure, arrhythmia, bradycardia, cardiac ischemia/reperfusion injury, cardiac fibrosis, etc. This study is aimed to clarify the role of higenamine in heart diseases. Higenamine has effects on improving energy metabolism of cardiomyocytes, anti-cardiac fibroblast activation, anti-oxidative stress and anti-apoptosis. Accumulating evidence from various studies has shown that higenamine exerts a wide range of cardiovascular pharmacological effects in vivo and in vitro, including alleviating heart failure, reducing cardiac ischemia/reperfusion injury, attenuating pathological cardiac fibrosis and dysfunction. In addition, several clinical studies have reported that higenamine could continuously increase the heart rate levels of healthy volunteers as well as patients with heart disease, but there are variable effects on systolic blood pressure and diastolic blood pressure. Moreover, the heart protection and therapeutic effects of higenamine on heart disease are related to regulating LKB1/AMPKα/Sirt1, mediating the β2-AR/PI3K/AKT cascade, induction of heme oxygenase-1, suppressing TGF-β1/Smad signaling, and targeting ASK1/MAPK (ERK, P38)/NF-kB signaling pathway. However, the interventional effects of higenamine on heart disease and its underlying mechanisms based on experimental studies have not yet been systematically reviewed. This paper reviewed the potential pharmacological mechanisms of higenamine on the prevention, treatment, and diagnosis of heart disease and clarified its clinical applications. The literature shows that higenamine may have a potent effect on complex heart diseases, and proves the profound medicinal value of higenamine in heart disease.
Highlights
Natural products represent an important source of compounds used in the discovery of new therapeutic agents (Harvey et al, 2015), which have relatively single compounds with good drug characteristics, including structural diversity and complexity, high selectivity and specific pharmacological activities, as well as novel therapeutic effects and mechanisms of action (Barnett and Stallforth, 2018; Ekiert and Szopa, 2020)
The results indicate that area under the concentration-time curve (AUC) increases proportionally with the dose increase of higenamine, and when the dose continues to increase, the percentage of higenamine excreted in the urine remains unchanged
Serum metabolomics analyses indicated that the therapeutic effects of higenamine on chronic heart failure (CHF) rats were primarily related to the comprehensively regulation of mitochondrial energy metabolism metabolites, including acetylphosphate, coenzyme
Summary
Natural products represent an important source of compounds used in the discovery of new therapeutic agents (Harvey et al, 2015), which have relatively single compounds with good drug characteristics, including structural diversity and complexity, high selectivity and specific pharmacological activities, as well as novel therapeutic effects and mechanisms of action (Barnett and Stallforth, 2018; Ekiert and Szopa, 2020). Based on the effectiveness and safety of clinical medicine practice, higenamine has attracted much attention as a promising chemical compound and natural product for the prevention, diagnosis, and treatment of heart disease. It is worth mentioning that higenamine has been approved for clinical research by the China Food and Drug Administration (CFDA) It has been approved by clinical trials to detect coronary artery stenosis and myocardial ischemia by myocardial perfusion imaging with certain specificity and safety (Zheng et al, 2005). Studies designed to evaluate the potential pharmacological effects and biological mechanisms of higenamine in the prevention, diagnosis, and treatment of heart disease are necessary for researchers. This study provided a synthetic summary of the recent research progress of higenamine on cardiovascular pharmacology and its mechanism of action, thereby contributing to the further clinical practice and application of the drug
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