Shakuyaku-Kanzo-To Prevents Angiotensin Ⅱ-Induced Cardiac Hypertrophy in Neonatal Rat Ventricular Myocytes

The global incidence of mortality due to heart failure (HF) is on the rise, presenting a significant challenge in various regions, including Japan. There is an urgent need for innovative prevention and treatment strategies to address this issue. Traditional medicine, particularly Japanese Kampo medicine (JKM), has been proposed as a potential therapeutic approach and has undergone examination in clinical trials related to HF. However, the deficiency of robust scientific evidence underscores the necessity for further exploration into the cardioprotective mechanisms of JKM. This study systematically examines the cardioprotective effects of Shakuyaku-kanzo-to (SKT), a specific JKM with limited application in cardiac care. Utilizing neonatal rat ventricular myocytes, we assessed the direct effects of SKT on myocardial hypertrophy. Methodologies included immunohistochemistry for cell size and a plate reader for quantifying cell survival, intracellular calcium levels ([Ca²⁺]_i), and reactive oxygen species (ROS) production. In addition, quantitative reverse transcription polymerase chain reaction (RT-PCR) was employed for gene expression analysis. The findings reveal that SKT significantly mitigates angiotensin Ⅱ (AngⅡ)-induced cardiomyocyte hypertrophy and cell death, while also reducing elevated [Ca²⁺]_i and ROS production associated with this condition. Furthermore, co-administration of nifedipine, an L-type Ca²⁺ channel (L-Ca²⁺) blocker, demonstrated that SKT antagonizes L-Ca²⁺ actions. These results indicate that SKT offers protection against AngⅡ-induced cardiomyocyte hypertrophy by inhibiting L-Ca²⁺-mediated pathways. Consequently, this research highlights the potential of SKT as a promising therapeutic agent for cardiac applications, paving the way for new preventive and treatment strategies for HF.