The occurrence of in-stent restenosis (ISR) poses a significant challenge for percutaneous coronary intervention (PCI). Thus, the promotion of vascular reendothelialization is essential to inhibit endothelial proliferation. In this study, we clarified the mechanism by which Detoxification and Activating Blood Circulation Decoction (DABCD) promotes vascular reendothelialization to avoid ISR by miRNA-126-mediated modulation of the vascular endothelial growth factor (VEGF) signaling pathway. A rat model of post-PCI restenosis was established by balloon injury. The injured aortic segment was collected 14 and 28 d after model establishment. Our findings indicate that on the 14th and 28th days following balloon injury, DABCD reduced intimal hyperplasia and inflammation and promoted vascular reendothelialization. Additionally, DABCD markedly increased NO expression and significantly decreased ET-1 production in rat serum. DABCD also increased the mRNA level of eNOS and the protein expression of VEGF, p-Akt, and p-ERK_1/2 in vascular tissue. Unexpectedly, the expression of miR-126a-5p mRNA was significantly lower in the aortic tissue of balloon-injured rats than in the aortic tissue of control rats, and higher miR-126a-5p levels were observed in the DABCD groups. The results of this study indicated that the vascular reendothelialization effect of DABCD on arterial intimal injury is associated with the inhibition of neointimal formation and the enhancement of vascular endothelial activity. More specifically, the effects of DABCD were mediated, at least in part, through miR-126-mediated VEGF signaling pathway activation.

Nonalcoholic steatohepatitis (NASH) is a subtype of nonalcoholic fatty liver disease (NAFLD) characterized by hepatic steatosis and evidence of hepatocyte injury (ballooning) and inflammation, with or without liver fibrosis. In this study, after 12 weeks of induction, the mice were treated with emodin succinyl ethyl ester (ESEE) for four weeks at doses of 10/30/90 mg/kg/day. The blood analysis of experimental endpoints showed that ESEE exhibited significant therapeutic effects on the progression of disorders of glycolipid metabolism and the induced liver injury in the model animals. Histopathological diagnosis of the liver and total triglyceride measurements revealed that ESEE had a significant therapeutic effect on the histopathological features of nonalcoholic fatty liver disease/hepatitis, such as cellular steatosis and activation of intrahepatic inflammation. Additionally, ESEE was able to improve hepatocyte fat deposition, steatosis, and the course of intrahepatic inflammatory activity. Furthermore, it showed some inhibitory effect on liver fibrosis in the model animals. In summary, this study confirms the therapeutic effects of ESEE on the NAFLD/NASH model in C57BL/6J mice induced by a high-fat, high cholesterol, and fructose diet. These effects were observed through improvements in liver function, inhibition of fibrosis, and inflammatory responses. Changes in blood glucose levels, blood lipid metabolism, liver histopathological staining, liver fibrosis staining, and related pathological scores further supported the therapeutic effects of ESEE. Therefore, this study has important implications for the exploration of novel drugs for nonalcoholic fatty liver disease.

Neuropathic pain is one of the most intractable diseases. The lack of effective therapy measures remains a critical problem due to the poor understanding of the cause of neuropathic pain. The aim of this study was to investigate the effect of dexmedetomidine (Dex) in trigeminal neuropathic pain and the underlying molecular mechanism in order to identify possible therapeutic targets. We used a chronic constriction injury (CCI) model of mice to investigate whether Dex prevents neuropathic pain and the inflammation response. The α 2-adrenoceptors (α2AR) inhibitor BRL44408 and adenovirus for knocking down High mobility group box 1 (HMGB1) was administrated to confirm whether Dex exert its effect through targeting α2AR and HMGB1. The results indicated that Dex significantly inhibited CCI induced neuropathic pain through targeting α2AR and HMGB1. Dex inhibited the inflammatory response through decreasing the release and the mRNA expression of IL-1β, IL-6, and TNF-ɑ while increasing that of IL-10. Moreover, Dex participates in the regulation of HMGB1, Toll-like receptor 4 (TLR4), NFκb (p-65) expression and the phosphorylation of IκB-ɑ. In conclusion, Dex could relieve neuropathic pain through α2AR and HMGB1 and attenuate inflammation response.