Abstract
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 AUC0-∞ 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 Cmax 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.
Highlights
Wogonin (5,7-dihydroxy-8-methoxyflavone, Figure 1) is one of the major flavonoids extracted from the root of Scutellaria baicalensis Gerogi (Scutellariae radix), a flowering plant that has long been known as a traditional remedy in East Asian countries [1]
Accuracies determined for intra- and inter-day were all within 100% ± 10% of the actual values
Taken together with metabolism results, these findings suggest that wogonin is mainly excreted as its conjugated form
Summary
Wogonin has been widely investigated for its antioxidant [2], anti-inflammatory [3,4], and anticancer activities [5,6]. With increasing evidence of its anticancer therapeutic potential and attractive toxicological properties [7,8,9,10,11], wogonin has been recognized as a promising lead compound for new anticancer drug development [12]. Various studies have suggested that wogonin exerts its anticancer effect through modulation of multiple molecular pathways. Wogonin induces apoptosis in hepatocellular carcinoma cells SK-HEP-1 via activation of caspase 3 and alternative expression of p21 protein [13]. Wogonin can induce apoptosis by activating the AMPK and p53 signaling pathways in human glioblastoma cells [14]
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