Sodium Houttuyfonate Inhibits Voltage-Gated Peak Sodium Current and Anemonia Sulcata Toxin II-Increased Late Sodium Current in Rabbit Ventricular Myocytes

Abstract

Aim: Sodium houttuyfonate (SH), a chemical compound originating from Houttuynia cordata, has been reported to have anti-inflammatory, antibacterial, and antifungal effects, as well as cardioprotective effects. In this study, we investigated the effects of SH on cardiac electrophysiology, because to the best of our knowledge, this issue has not been previously investigated. Methods: We used the whole-cell patch-clamp technique to explore the effects of SH on peak sodium current (I_Na.P) and late sodium current (I_Na.L) in isolated rabbit ventricular myocytes. To test the drug safety of SH, we also investigated the effect of SH on rapidly activated delayed rectifier potassium current (I_Kr). Results: SH (1, 10, 50, and 100 μmol/L) inhibited I_Na.P in a concentration-dependent manner with an IC₅₀ of 78.89 μmol/L. In addition, SH (100 μmol/L) accelerated the steady state inactivation of I_Na.P. Moreover, 50 and 100 μmol/L SH inhibited Anemonia sulcata toxin II (ATX II)-increased I_Na.L by 30.1 and 57.1%, respectively. However, SH (50 and 100 μmol/L) only slightly affected I_Kr. Conclusions: The inhibitory effects of SH on ATX II-increased I_Na.L may underlie the electrophysiological mechanisms of the cardioprotective effects of SH; SH has the potential to be an effective and safe antiarrhythmic drug.

Novel Meroterpenoids from Hypericum patulum: Highly Potent Late Nav1.5 Sodium Current Inhibitors

“…Compound 2 showed equal and significant inhibitions on the late I Na by both approaches (Figure and Figure S5). The IC 50 value of 2 is 0.2 μM, which is about 1/100 of that of Ranolazine (Ran, a late I Na inhibitor clinically used as a first-line drug for chronic angina) and comparable to that of GS-6615 (the most potent synthetic inhibitor) . To the best of our knowledge, 2 is the most potent natural late I Na inhibitor so far.…”

“…In last 15 years, synthetic late I Na inhibitors, exemplified by ranolazine, GS-458967, GS-462808, and GS6615, have been discovered and proved to be of benefit for treating ischemia, angina, and arrhythmias as well as for improving ventricular pump function. , With regards to natural products (NPs), tetrodotoxin played a critical role in the discovery of late I Na , but only few natural product modulators of late I Na are known (resveratrol, sodium houttuyfonate, and barbaloin) . Considering that NPs are an important resource for the discovery of new drug leads and most synthetic late I Na inhibitors are derivatives of ranolazine, it is of interest to explore new types of late I Na blockers from NPs.…”