Wogonin is a natural anticancer candidate. The purpose of this study was to explore the pharmacokinetic profiles, tissue distribution, excretion and plasma protein binding of wogonin in Sprague-Dawley rats. A rapid, sensitive, and specific LC-MS/MS method has been developed for the determination of wogonin in different rat biological samples. After i.v. dosing of wogonin at different levels (10, 20 and 40 mg/kg) the elimination half-life was approximately 14 min, the AUC 0-∞ increased in a dose disproportional manner from 112.13 mg/L·min for 10 mg/kg to 758.19 mg/L·min for 40 mg/kg, indicating a non linear pharmacokinetic profile. After i.g. dosing at 100 mg/kg, plasma levels of wogonin peaked at 28 min with a C max value of 300 ng/mL and a very low oral bioavailability (1.10%). Following i.v. single dose (20 mg/kg), wogonin was detected in all examined tissues (including testis) with the highest levels in kidney and liver. Approximately 21% of the administered dose was excreted as unchanged drug (mainly via non-biliairy fecal route (16.33%). Equilibrium dialysis was used to evaluate plasma protein binding of wogonin at three concentrations (0.1, 0.5 and 2 µg/mL). Results indicated a very high protein binding degree (over 90%), reducing substantially the free fraction of the compound.
Palmitoyl ascorbate (PA) as an antioxidant has the potential for the treatment of cancer. In the present study, a nanocarrier system was developed for co-delivery of docetaxel (DOC) with palmitoyl ascorbate and the therapeutic efficacy of a combination drug regimen was investigated. For this purpose, different ratios of docetaxel and palmitoyl ascorbate were co-encapsulated in a liposome and they all showed high encapsulation efficiency. The average diameters of the liposomes ranged from 140 to 170 nm. Negative zeta potential values were observed for all systems, ranged from −40 mV to −56 mV. Studies on drug release and cellular uptake of the co-delivery system demonstrated that both drugs were effectively taken up by the cells and released slowly. Moreover, the liposome loading drugs with DOC/PA concentration ratio of 1:200 showed the highest anti-tumor activity to three different types of tumor cells. The higher in vivo therapeutic efficacy with lower systemic toxicity of the DOC-PA200-LPs was also verified by the H22 tumor bearing mice model. Our results showed that such co-loaded delivery systems could serve as a promising therapeutic approach to improve clinical outcomes against hepatic carcinoma.
Background
The aim of this study was to assess the hypoglycemic effect of
Cyclocarya paliurus
extract (CPE) on diabetes mellitus (DM) mice.
Material/Methods
A DM mouse model was established to test FBG, TC, and TG. The DM mice were divided into 3 groups: a DM group, a DM+CPE (0.5 g/Kg) group, and a DM+CPE (1.0 g/Kg) group. The FBG and body weight were measured. The glucose tolerance ability was determined by OGTT test. FINS was measured to calculate ISI and IRI. Serum MDA, SOD, and GSH-Px levels were detected. NIT-1 cells were cultured
in vitro
and divided into 4 groups: a control group, a STZ group, a STZ+CPE (80 μg/mL) group, and a STZ+CPE (160 μg/mL) group. Cell apoptosis and ROS content were assessed by flow cytometry. Cell proliferation was detected by EdU staining.
Results
Compared with the control group, FBG, TC, and TG were significantly increased in the DM group. CPE gavage obviously reduced FBG level, increased body weight, enhanced glucose tolerance, elevated FINS level and ISI, and reduced IRI, all in a dose-dependent manner. CPE gavage reduced serum MDA content and increased SOD and GSH-Px enzyme activities in DM mice. STZ markedly enhanced ROS production, induced apoptosis, and inhibited proliferation in NIT-1 cells. CPE treatment clearly reduced ROS production and apoptosis, enhanced cell proliferation, and alleviated STZ damage to NIT-1 cells.
Conclusions
CPE has the effects of decreasing blood glucose and insulin resistance, and enhancing glucose tolerance in DM mice, which may be related to its effects of reducing oxidation and reduced apoptosis, and relieving STZ in pancreatic beta cell injury.
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