Astragali Radix−Notoginseng Radix et Rhizoma medicine pair prevents cardiac remodeling by improving mitochondrial dynamic balance

Astragali Radix and Notoginseng Radix et Rhizoma are commonly used in the treatment of cardiovascular diseases. However, whether Astragali Radix−Notoginseng Radix et Rhizoma medicine pair (AN) can improve cardiac remodeling and the underlying mechanism is still unclear. This study aimed to evaluate the cardioprotective effect and potential mechanism of AN on cardiac remodeling by using the method of transverse constriction of the aorta (TAC) to mice and angiotensin II-induced neonatal rat cardiomyocytes and fibroblasts in vitro. HPLC-Q-TOF-MS/MS was used to characterize the 23 main components of AN. AN significantly improved the cardiac function of mice induced with TAC. In addition, AN significantly reduced levels of NT-proBNP, CTn-T and IL-6 in the serum and improved inflammatory cell infiltration. Then, the size of TAC-induced hearts was close to normal after AN treatment. AN improved the cross-sectional area of cardiomyocytes and alleviated the upregulation of cardiac hypertrophy marker genes (ANP, BNP and MYH7) in vivo and in vitro. Meanwhile, AN alleviated collagen deposition in TAC-induced mice. AN also reduced the expression of fibrosis-related indicators (COL1A1 and COL3A1) and inhibited the activation of the TGF-β1/Smad3 pathway. Therefore, AN could improve TAC-induced cardiac remodeling. Furthermore, AN downregulated p-Drp1 (Ser616) expression and upregulated the expression of MFN-2 and OPA1 in vivo and in vitro, thereby restoring the balance between mitochondrial fusion and fission. In conclusion, this study elucidated that AN could improve cardiac remodeling by regulating mitochondrial dynamic balance, which provided experimental data for the rational application of Chinese medicine prescription with AN as the main component in clinical practice.