Ginsenoside Rg1 exerts anti-arrhythmic effect by inhibiting I CaL through cAMP-PKA and PI3K-AKT signaling pathways in rat ventricular myocytes after myocardial ischemia-reperfusion injury

Figure 1.. The effects of Rg1 on the L-type calcium current (ICaL) of rat ventricular myocytes, current–voltage relationship, and concentration-dependence in rat ventricular myocytes. (A–F) represent control group (A) and five experimental groups treated with Rg1 at concentrations of Rg1: 20, 40, 80, 160, and 320 mg/L, respectively; (G) shows the effect of Rg1 on the current–voltage relationship curve of ICaL; and (H) shows the concentration-dependence effect of Rg1 on ICaL. (*P < .05 vs Control group; #P < .05 vs I/R group).

Figure 2.. Effects of Rg1-IPost treatments on cardiac function, dynamic action potential duration restitution (APDR), and its slope factor in myocardial I/R injury. (A) and (B) show representative heart function in the I/R group and Rg1-IPost group, respectively. (C) and (D) compare the percentage recovery of left ventricular developed pressure (LVDP) and the extent of reperfusion-induced spasm between the two groups. (E) and (H) show the single exponential function fitting curves of APD90 at different pacing intervals (PI) and the corresponding fast time constant (τ). (F) and (I) show the exponential restitution curves of APD90 at different diastolic intervals (DI) and the associated τ values. (G) and (J) compare the maximum slope factor (f) of the APD90 restitution curve across different diastolic intervals (DI). (*P < .05 vs Control group; #P < .05 vs I/R group).

Figure 3.. Effects of Rg1-IPost treatment on action potential duration (APD) alternans in myocardial I/R injury. (A, B, and C) show electrical alternans of APD90 at different pacing intervals (PI) in the control group, I/R group, and Rg1-IPost group, respectively. (D) illustrates the changes in PI, corresponding APD90, and the occurrence of 2:1 capture in each group. (E) shows the amplitude of APD90 alternans, calculated as the difference between the maximum and minimum APD90 values in each group. (*P < .05 vs Control group; #P < .05 vs I/R group).

Figure 4.. Effects of Rg1-IPost on the induction of ventricular tachycardia (VT) in myocardial I/R injury. (A), (B), and (C) illustrate the types and duration of ventricular tachyarrhythmia induced at different pacing intervals (PI) in the control group, I/R group, and Rg1-IPost group, respectively. (D) shows the comparison of PI thresholds required to induce VT among the three groups. (E) presents the incidence rates of VT in each group.(*P < .05 vs Control group; #P < 0.05 vs I/R group).

Figure 5.. Effects of Rg1-IPost on the ICaL, its I–V relationship curve, and the steady-state activation and inactivation curves of ICaL in ventricular myocytes in myocardial I/R injury. A, B, and C show representative ICaL traces in ventricular myocytes from the control group, I/R group, and Rg1-IPost group, respectively. (D) compares the I–V relationship curve of ICaL in ventricular myocytes among the control group, I/R group, and Rg1-IPost group. (E) and (F) illustrate the steady-state activation and inactivation curves of ICaL in the control group, I/R group, and Rg1-IPost group, respectively. (G) compares the maximum half-inactivation potential of steady-state activation and inactivation in the control group, I/R group, and Rg1-IPost group. (H) presents the slope factor of steady-state activation and inactivation in the control group, I/R group, and Rg1-IPost group. (*P < .05 vs Control group; #P < .05 vs I/R group).

Figure 6.. Effects of Rg1-IPost on the steady-state activation and inactivation curves of ICaL in ventricular myocytes following myocardial I/R injury. (A) and (B) shows the steady-state activation and inactivation curves in the control group, I/R group, and Rg1-IPost group, respectively. (C) compares the maximum half-inactivation potential of steady-state activation and inactivation in the control group, I/R group, and Rg1-IPost group. (D) presents the slope factor of steady-state activation and inactivation in the control group, I/R group, and Rg1-IPost group. (*P < .05 vs Control group; #P < .05 vs I/R group).

Figure 7.. Effects of ginsenoside Rg1 on cAMP-PKA and PI3K-AKT signaling pathways during IR injury. (A) Western blot analysis of cAMP and p-PKA levels in cardiomyocytes following IR injury with or without Rg1 treatment. IR significantly increased cAMP and p-PKA expression, while Rg1 treatment reversed these effects. (B) Quantification of cAMP and p-PKA protein levels normalized to GAPDH as a loading control. (C) Western blot analysis showing the expression of p-AKT and AKT in cardiomyocytes after IR injury with or without Rg1 treatment. IR significantly reduced p-AKT levels, whereas Rg1 treatment increased p-AKT expression, restoring the activation of the PI3K-AKT pathway. (D) Quantification of p-AKT and AKT protein levels normalized to GAPDH (n = 3). (*P < .05 vs Control group; #P < .05 vs I/R group).