Aqueous Extract of Whitmania Pigra Whitman Alleviates Thrombus Burden Via Sirtuin 1/NF-κB Pathway.

BACKGROUND: Whitmania pigra Whitman (W pigra), a traditional Chinese medicine, has functions of breaking stagnant and eliminating blood stasis. The aim of this study was to investigate the underlying mechanism of W pigra against deep vein thrombosis (DVT). METHODS: A rat model of DVT induced by inferior vena cava stenosis was successfully established. Rats were administered vehicle (saline solution, p.o.), three doses of W pigra aqueous extract (34.7, 104.2, or 312.5 mg crude W pigra/kg, p.o.), heparin (200 U/kg, i.v.), or clopidogrel (25 mg/kg, p.o.) once daily for 2 d. Thrombus weight and histopathological changes were examined. Blood samples were collected to determine blood cell counts, blood viscosity, blood coagulation, blood fibrinolysis, serum levels of interleukin-1ß, and tumor necrosis factor-α. Protein expressions of Sirtuin1 (SIRT1), acetylated p65 (Ace-p65), and phosphorylated p65 (p-p65) were determined by Western blot. Furthermore, SIRT1-specific inhibitor EX527 was applied to confirm the role of SIRT1 in the antithrombotic effect of W pigra. RESULTS: W pigra significantly decreased thrombus weight. W pigra had no effects on blood cell counts, whole blood viscosity, blood coagulation, blood fibrinolysis. However, it reduced tissue factor protein expression in the vein wall and thrombus. Moreover, it sharply increased SIRT1 protein expression and decreased leukocytes recruitment in the thrombus and vein wall, serum levels of interleukin-1ß and tumor necrosis factor-α, and protein expressions of Ace-p65 and p-p65. Furthermore, the antithrombotic effect of W pigra was significantly abolished by EX527. CONCLUSIONS: Aqueous extract of W pigra effectively reduced DVT burden by inhibiting inflammation via SIRT1/nuclear factor-kappa B signaling pathway.

Evaluation of tetrandrine sustained release calcium alginate gel beads in vitro and in vivo.

An approach for the preparation of tetrandrine sustained release calcium alginate gel beads was described. In vitro the release of tetrandrine from sustained release dosage forms went on a time of 12 hours which fitted non-Fickian diffusion with matrix erosion significantly. In vivo the plasma concentration of tetrandrine extended preparation given in dogs reached Cmax 2.67+/-0.69 microg/ml approximately at 5.67+/-0.58 h after oral administration. The AUC0-->24 and AUC0-->infinity were 24.64+/-6.77 mg.h/l and 29.75+/-5.30 mg.h/l, respectively. The elimination half-time was 9.6+/-2.40 h. While a favorable correlation existed between in vitro and in vivo with a correlative coefficient of 0.9798 through linear regression. An investigation on the quantitative relationship between in vitro release and in vivo absorption is a highly necessary work guided for manufacture, optimization and in vivo evaluation of sustained release dosage by means of in vitro release or dissolution tests.