Japanese herbal medicine Toki-shakuyaku-san (TJ-23) enhances cardiac contractile function in isolated ventricular cardiomyocytes

Toki-shakuyaku-san (TJ-23), a Japanese traditional herbal medicine, has a long history in Asia for the treatment of neurodegenerative, immune, and airway diseases. However, the effect of TJ-23 on heart function has not been elucidated. This study was designed to examine the effect of TJ-23 on ventricular contractile function at the single cardiomyocyte level. Ventricular cardiomyocytes from adult rat hearts were stimulated to contract at 0.5 Hz, and mechanical properties were evaluated using an IonOptix Myocam system. Contractile properties analyzed included peak shortening (PS), time-to-PS (TPS), time-to-90% relengthening (TR90), and maximal velocity of shortening/relengthening (+/-dL/dt). TJ-23 (10(-8)-10(-5) mg/ml) exhibited significant augmentation in PS, with a maximal response of 27.2%. TJ-23 at 10(-7)-10(-5) mg/ml also increased +/-dL/dt, shortened TR90, while had no effect on TPS. Pretreatment with the Na+-K+-ATPase inhibitor ouabain (I-muM), removal of extracellular sodium from contractile buffer (which inhibits Na+/Ca2+ exchanger), or both concurrently abolished the positive effect of TJ-23 in cell shortening without inhibiting the baseline cell shortening. This study demonstrated a direct cardiac stimulatory action of TJ-23 at the cardiomyocyte level, which may be related to, at least in part, a Na+/K+-ATPase and/or Na+/Ca2+ exchanger-dependent mechanism.