Active substances and molecular mechanisms of the anti-myocardial ischemia effects of Carthami flos by network pharmacology and in vitro experiments

Abstract

Myocardial ischemia is a predominant cardiovascular disorder that can result in a series of life-threatening cardiovascular diseases. Carthami flos (CF), the flower of Carthamus tinctorius L., is a commonly used herbal medicine in Chinese medicine for treating coronary atherosclerotic heart diseases based on its anti-myocardial ischemia (MI) effects. This paper aimed to investigate the active substances and mechanisms of the anti-MI effects of CF by network pharmacology and in vitro experiments. The results indicated that 9 constituents showed high degree of association with multiple targets of MI, including quercetin, kaempferol, β-sitosterol, luteolin, baicalein, safflomin A, safflomin C, safflower-yellow-B and hydroxysafflor yellow A. In addition, AKT1, EGFR, CASP3, MYC, JUN, ALB, CTNNB1, VEGFA, ESR1, and IL1B were screened as the leading targets with a degree number ≥50. Bioinformatic annotation of GO-MF and KEGG showed that the anti-MI effects of CF are related to apoptosis and response to antioxidative stress pathways. The in vitro results showed that CF reduced LDH and CK levels, alleviated cell cycle arrest, and decreased ROS levels in H2O2-treated H9c2 cells. In addition, CF also promoted the nuclear shift of Nrf2 and the mRNA expressions of Akt, Nrf2 and Bcl-2 but decreased the expression of caspase-3 in H2O2-treated H9c2 cells. Collectively, the anti-MI effects of CF involve inhibiting apoptosis and antioxidative stress in cardiomyoblasts by regulating Akt/Nrf2/Caspase-3/Bcl-2, and the possible active substances of CF are quercetin, kaempferol, β-sitosterol, luteolin, baicalein, safflomin C, safflower-yellow-B, and hydroxysafflor yellow A. The results of this study will be helpful for further drug development of CF and its active monomers.