[Value of ginsenoside Rb1 in alleviating coronary artery lesion in a mouse model of Kawasaki disease].

OBJECTIVE: To study the effect and related signaling pathways of ginsenoside Rb1 in the treatment of coronary artery lesion (CAL) in a mouse model of Kawasaki disease (KD).
METHODS: BALB/c mice were randomly divided into a control group, a model group, an aspirin group, a low-dose ginsenoside Rb1 group (50 mg/kg), and a high-dose ginsenoside Rb1 group (100 mg/kg), with 12 mice in each group. All mice except those in the control group were given intermittent intraperitoneal injection of 10% bovine serum albumin to establish a mouse model of KD. The mice in the aspirin group, the low-dose ginsenoside Rb1 group, and the high-dose ginsenoside Rb1 group were given the corresponding drug by gavage for 20 days after modeling. Hematoxylin and eosin staining was used to observe the pathological changes of coronary artery tissue. ELISA was used to measure the levels of the inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in serum and coronary artery tissue. Western blot was used to measure the relative expression levels of proteins involved in the regulation of the AMPK/mTOR autophagy signaling pathway and the PI3K/Akt oxidative stress signaling pathway in coronary artery tissue.
RESULTS: The observation of pathological sections showed that compared with the model group, the high-dose ginsenoside Rb1 group had significant improvement in the symptoms of vascular wall thickening, intimal edema, fiber rupture, and inflammatory infiltration of endothelial cells. Compared with the control group, the model and low-dose ginsenoside Rb1 groups had significant increases in the levels of TNF-α, IL-6, and IL-1β in serum and coronary artery tissue (P<0.05); the model group had significant increases in the expression levels of P-AMPK/AMPK, P-mTOR/mTOR, and P-P70S6/P70S6 in coronary artery tissue (P<0.05) and significant reductions in the expression levels of P-PI3K/PI3K, P-AKT/AKT, and P-GSK-3β/GSK-3β in coronary artery tissue (P<0.05). Compared with the model group, the aspirin group and the high-dose ginsenoside Rb1 group had significant reductions in the levels of TNF-α, IL-6, and IL-1β (P<0.05); the low- and high-dose ginsenoside Rb1 groups had significant reductions in the expression levels of P-AMPK/AMPK, P-mTOR/mTOR, and P-P70S6/P70S6 (P<0.05) in a dose-dependent manner between the two groups (P<0.05); the low-dose ginsenoside Rb1 group had no significant change in the expression level of P-PI3K/PI3K (P>0.05) and had significant increases in the expression levels of P-AKT/AKT and P-GSK-3β/GSK-3β (P<0.05), while the high-dose ginsenoside Rb1 group had significant increases in the relative protein expression levels of the above three proteins (P<0.05). Compared with the low-dose ginsenoside Rb1 group, the aspirin group and the high-dose ginsenoside Rb1 group had significant reductions in the levels of TNF-α, IL-6, and IL-1β (P<0.05); the high-dose ginsenoside Rb1 group had significant increases in the expression levels of P-PI3K/PI3K and P-AKT/AKT (P<0.05).
CONCLUSIONS: Ginsenoside Rb1 can effectively alleviate CAL in a mouse model of KD in a dose-dependent manner, possibly by regulating the AMPK/mTOR/P70S6 autophagy signaling pathway to inhibit CAL inflammation and regulating the PI3K/AKT/GSK-3β oxidative stress signaling pathway to exert a biological activity of protection against coronary artery endothelial cell injury.