Dohongsamul-tang inhibits cardiac remodeling and fibrosis through calcineurin/NFAT and TGF-β/Smad2 signaling in cardiac hypertrophy

Ethnopharmacological relevance: Dohongsammul-tang (DH) is a Korean traditional herbal medicine used to alleviate symptoms caused by extravasated blood. It is known to protect against cardiovascular diseases and promote blood circulation by activating blood circulation to dispel blood stasis. The DH based on the characteristics of its medicinal properties has discovered the potential of alleviating cardiac hypertrophy. Therefore, this study was performed to verify the pharmacological effect of DH on improving cardiovascular disorders and to demonstrate its mutual improvement effect on renal function. Furthermore, aim of this study is founding the new potential beyond the traditional medicinal efficacy of DH, a traditional medicine. Aim of the study: In cardiovascular disease, cardiac hypertrophy refers to a change in the shape of the heart's structure due to pressure overload. It is known that an increase in myofibrils causes thickening of the heart, resulting in high blood pressure. Therefore, suppressing cardiac hypertrophy may be a major factor in lowering the morbidity, mortality, and heart failure associated with cardiovascular disease. Therefore, the study was performed to investigate whether DH, traditionally used, has effects on improving and alleviating cardiac injury and fibrosis caused by cardiac hypertrophy. Materials and methods: Dohongsamul-tang was composed of 6 herbal medicine and each material were boiled with 4 L distilled water for 2 h. The mixture for dohongsamul-tang centrifuged at 3000 rpm for 10 min and concentrated. The concentrated dohongsamul-tang extraction freeze-dried and sotred at 70 degrees C. The powder of dohongsamul-tang was diluted with distilled water and administered orally. In this study, pressure overload was induced by tying the transverse aortic arch, which is connected to the left ventricle, to the thickness of a 27G needle by performing a surgical operation. The resulting cardiac hypertrophy and heart remodeling was induced and maintained for 8 weeks. Results: The study administered propranolol and dohongsamul-tang orally for 10 weeks to investigate their effects on cardiac hypertrophy induced by transverse aortic contraction (TAC) surgery. Results showed that TAC group increased the left ventricle weight and decreased cardiac function, but dohongsamul-tang treatment attenuated these effects. The pressure-volume curve experiment revealed that dohongsamul-tang improved cardiovascular function, which was worsened by TAC group. Dohongsamul-tang treatment also downregulated collagen I and III through the TGF-& beta;/Smad2 signaling pathway and improved hematological biomarkers of cardiac hypertrophy. In addition, dohongsamul-tang treatment improved renal function-related biomarkers, such as blood creatinine, blood urea nitrogen, and neutrophil gelatinase-associated lipocalin, which were increased by TAC-induced cardiac hypertrophy. Conclusions: Taken together, dohongsamul-tang treatment inhibited cardiac remodeling due to pressure overload in the TAC-induced cardiac hypertrophy model, and this effect is thought to be manifested by improving the functional and morphological changes through the calcineurin/NFATc4 and reducing the cardiac fibrosis by suppressing TGF-& beta;/Smad2 signaling pathways.