Effect of Jingfang Granules on carrageenan-induced tail thrombosis in mice based on ERK/p38 MAPK signaling pathway / 中国中药杂志

ABSTRACT

The present study explored the anti-inflammatory and anti-thrombotic mechanism of Jingfang Granules on tail thrombosis induced by carrageenan in mice. Thirty-two male ICR mice were randomly divided into a control group, a model group, a Jingfang Granules group, and a positive drug(aspirin) group, with eight mice in each group. The thrombosis model was induced by intraperitoneal injection of carrageenan(45 mg·kg~(-1)) combined with low-temperature stimulation, and the mice were treated with drugs for 7 days before modeling. Twenty-four hours after modeling, blood was detected for four blood coagulation indices in each group. The enzyme-linked immunosorbent assay(ELISA) was used to detect the activity of plasma interleukin-6(IL-6), interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), and other inflammatory factors. The tails of mice in each group were cut off to observe tail lesions and measure the length of the thrombus. The protein expression and phosphorylation level of extracellular signal-regulated kinase 1/2(ERK1/2) and p38 mitogen-activated protein kinase(p38 MAPK) in spleen tissues were detected by Western blot. The results showed that dark red thrombus appeared in the tails of mice in each group. The length of the black part accounted for about 40% of the total tail in the model group. Additionally, the model group showed prolonged prothrombin time(PT), increased fibrinogen(FIB) content, and shortened activated partial thromboplastin time(APTT). Compared with the model group, the groups with drug intervention displayed shortened black parts in the tail and improved four blood coagulation indices(P<0.05). As revealed by ELISA, the expression levels of TNF-α, IL-1β, and IL-6 in the mouse plasma were significantly up-regulated in the model group, and those in the groups with drug intervention were reduced as compared with the model group(P<0.05). As demonstrated by Western blot, the protein expression and phosphorylation levels of ERK1/2 and p38 MAPK in the spleen tissues were significantly elevated in the model group, while those in the Jingfang Granules group were down-regulated as compared with the model group with a significant difference. Jingfang Granules can inhibit tail thrombosis of mice caused by carrageenan presumedly by inhibiting the activation of ERK1/2 and p38 MAPK signaling pathways.