The Effects of Puerarin on Rat Ventricular Myocytes and the Potential Mechanism

Abstract

Puerarin, a known isoflavone, is commonly found as a Chinese herb medicine. It is widely used in China to treat cardiac diseases such as angina, cardiac infarction and arrhythmia. However, its cardioprotective mechanism remains unclear. In this study, puerarin significantly prolonged ventricular action potential duration (APD) with a dosage dependent manner in the micromolar range on isolated rat ventricular myocytes. However, submicromolar puerarin had no effect on resting membrane potential (RMP), action potential amplitude (APA) and maximal velocity of depolarization (Vmax) of action potential. Only above the concentration of 10 mM, puerarin exhibited more aggressive effect on action potential, and shifted RMP to the positive direction. Millimolar concentrations of puerarin significantly inhibited inward rectified K+ channels in a dosage dependent manner, and exhibited bigger effects upon Kir2.1 vs Kir2.3 in transfected HEK293 cells. As low as micromolar range concentrations of puerarin significantly inhibited Kv7.1 and IKs. These inhibitory effects may due to the direct inhibition of puerarin upon channels not via the PKA-dependent pathway. These results provided direct preclinical evidence that puerarin prolonged APD via its inhibitory effect upon Kv7.1 and IKs, contributing to a better understanding the mechanism of puerarin cardioprotection in the treatment of cardiovascular diseases.

Inhalation of printer-emitted particles impairs cardiac conduction, hemodynamics, and autonomic regulation and induces arrhythmia and electrical remodeling in rats

“…Meanwhile, PEPs impeded acceleration of repolarization during increased heart rate (i.e., repolarization reserve), manifesting as prolonged QTc, TpTe, and TpTe/QT during stress up through 5 weeks after exposure. To prevent arrhythmia during sympathetic-induced increases in heart rate, healthy cardiomyocytes (rat and human) accelerate repolarization by enhancing the IK s current [104] via K v 7.1 phosphorylation [61]. Importantly, the long-term physiologic effects of PEPs resembled patients with concealed Long QT (LQT) Syndrome 1, who have a mutation in K v 7.1 (a major phosphorylation target of β 1 AR [61]) and prolonged QT and TpTe only during sympatho-excitation [62,63].…”

Puerarin alters the function of monocytes/macrophages and exhibits chondroprotection in mice

“…Additionally, puerarin ameliorates nerve injury-induced depression and pain following spared nerve injury in an arginase 2-dependent manner (27). Furthermore, puerarin attenuates mechanical and chemical nerve injuries in experimental models of cerebral ischemia, diabetic complication and cardiac diseases (6,8,13). These findings indicated the antioxidative, anti-inflammatory and antiapoptotic activities of puerarin in vivo and in vitro.…”

“…Puerarin is a phytoestrogen with potential beneficial effects in attenuating neuronal injury, diabetic kidney disease and heart failure (4-7). The herbal compound modulates oxidative stress and inflammatory responses in cardiovascular diseases (8). Furthermore, it has been reported that puerarin may be beneficial in treating diabetes mellitus (5).…”

Puerarin Enhances Ca2+ Reuptake and Ca2+ Content of Sarcoplasmic Reticulum in Murine Embryonic Stem Cell-Derived Cardiomyocytes via Upregulation of SERCA2a

“…Ohwi , has been wildly utilized in the treatment of cardiovascular diseases [17-18]. So far, anti-inflammatory [19], anti-oxidative [20] and anti-arrhythmia [21] effects of puerarin have been proven. Puerarin also shows acute inhibitory effects on the functional ion channels, such as Na + channels [12], inward rectified K + channels [21] and LTCC [22], in isolated CMs.…”

“…So far, anti-inflammatory [19], anti-oxidative [20] and anti-arrhythmia [21] effects of puerarin have been proven. Puerarin also shows acute inhibitory effects on the functional ion channels, such as Na + channels [12], inward rectified K + channels [21] and LTCC [22], in isolated CMs. Accumulated studies have shown that the PI3K/Akt, JAK/STAT, JNK, ERK1/2 and MAPK signaling pathways mediate the bio-effects of puerarin on various types of cells, i.e CMs [2, 17, 20], astrocytes [23], neurons [24], and retinal ganglion cells [10].…”