Tongqiaohuoxue decoction ameliorates obesity-induced inflammation and the prothrombotic state by regulating adiponectin and plasminogen activator inhibitor-1

Tongqiaohuoxue decoction (THD), a water extract of a mixture of eight species of medicinal herbs, has been used for the treatment of blood stasis and hypercoagulation in traditional East Asian medicine since 18th century.To investigate the in vivo efficacy of THD using high-fat diet (HFD)-induced obese mice with chronic inflammation and a prothrombotic state as an early vascular model.THD was prepared by hot water extraction and freeze-drying. Male C57BL/6 mice were divided into three groups. Group 1 (NC) mice were fed normal chow. Mice in group 2 (HFD) and 3 (HFD+THD) were fed with HFD for 12 weeks. In addition, Group 3 mice were administered with 100mg/kg body weight THD for 4 weeks after onset of obesity by HFD for 8 weeks. Glucose tolerance tests and histological tissue examinations were performed. The levels of adipokines, inflammatory markers, and prothrombotic markers were assessed.The oral administration of THD for 4 weeks had no effect on the liver, adipose tissue, or total body weight when the HFD and HFD+THD groups were compared. Nevertheless, mice treated in THD interestingly showed a significant increase in adiponectin in blood and adipose tissue. To verify the effect of THD on adiponectin, 3T3-L1 adipocytes were treated with THD; it stimulated adiponectin production in a dose-dependent manner. In the HFD+THD group, pro-inflammatory cytokines were significantly down-regulated in the blood, adipose tissue, and liver. Insulin resistance was also notably improved by THD. Simultaneously, THD significantly reduced plasminogen activator inhibitor-1 (PAI-1) levels in serum, adipose tissue, and liver. Fibrin deposition and tPA activity, downstream targets of PAI-1, were also notably reduced in the HFD+THD group compared to the HFD group.THD improved obesity-induced inflammation and insulin resistance by increasing adiponectin production. Additionally, THD administration exerted an anti-thrombotic effect through the regulation of PAI-1 and fibrinolysis. This study demonstrates the efficacy of a traditional East Asian medicine by providing scientific evidence and suggesting a possible mechanism of action.