Identification of the metabolites of baicalein in human plasma.

The metabolites of baicalein in human plasma were investigated after taking baicalein, which is one of the main bioactive flavones in Scutellaria baicalensis Georgi. Five metabolites (M1-M5) together with the parent drug baicalein (P) were detected and identified by the HPLC-diode-array detector (DAD) and LC-MS/MS methods. Among them, 7-methoxybaicalein 6-O-glucuronide (M5) is a new metabolite. Based on the results, the proposed metabolic pathway of baicalein in humans was inferred.

[Study on bile excretion of scutellarein].

OBJECTIVE: A HPLC-ECD method was established to determine scutellarin in rat bile. METHOD: The analytical column was Prontosil C18 (4.6 mm x 250 mm, 5 microm), and the mobile phase was consisted of methanol, 50 mmol x L(-1) phosphate buffer (adjusted by phosphoric acid to pH 2. 6), and tetrahydrofuran (40: 60: 10) , the flow rate was 1.0 mL x min(-1); the potential electrode voltage was 100 mv. RESULT: Concentration profile of scutellarin in rat bile was shown in this paper after oral administration of scutellarein. CONCLUSION: Only scutellarin was detected in rat bile, while both of scutellarin and scutellarein were detected in rat plasma.

Structural characterization of minor metabolites and pharmacokinetics of ganoderic acid C2 in rat plasma by HPLC coupled with electrospray ionization tandem mass spectrometry.

The metabolites and pharmacokinetics of ganoderic acid C2 (GAC2), a bioactive triterpenoid in Ganoderma lucidum in rat plasma were investigated by high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS). Totally, ten minor phase I metabolites of GAC2 were characterized after oral administration of GAC2, on the basis of their mass fragmentation pathways or direct comparison with authentic compounds by high-performance liquid chromatography coupled with diode array detection and electrospray ion trap tandem mass spectrometry (HPLC-DAD-ESI-MS(n)), and liquid chromatography coupled with electrospray ionization hybrid ion trap and time-of-flight mass spectrometry (LC-ESI-IT-TOF/MS) methods. Moreover, a rapid and specific method for quantification of GAC2 in rat plasma after oral administration was developed by using a liquid-liquid extraction procedure and HPLC-ESI-MS/MS analysis. It is the first time to report the metabolites and pharmacokinetics of GAC2.

Identification of major compounds in rat bile after oral administration of total triterpenoids of Ganoderma lucidum by high-performance liquid chromatography with electrospray ionization tandem mass spectrometry.

Triterpenoids are the main bioactive components of Ganoderma lucidum, a famous traditional Chinese medicine. After oral administration of total triterpenoids of G. lucidum (TTGL), the rat bile was analyzed by high-performance liquid chromatography coupled with diode array detection and electrospray ion trap tandem mass spectrometry (HPLC-DAD-ESI-MS(n)) and liquid chromatography coupled with electrospray ionization hybrid ion trap and time-of-flight mass spectrometry (LC-ESI-IT-TOF/MS). From rat bile and TTGL samples, a total of 31 triterpenoids, including seven new compounds, were identified or tentatively characterized based on their fragmentation behaviors. Among them, 22 triterpenoids were identified from TTGL and 29 triterpenoids were detected from rat bile after oral administration of TTGL. The results indicated that the majority of triterpenoids detected in TTGL extract could be excreted through rat bile. It is the first report on excretion of total triterpenoids of G. lucidum in rat bile.

Antifibrotic effects of chronic baicalein administration in a CCl4 liver fibrosis model in rats.

Baicalein was a major bioactive flavonoid derived from Radix Scutellariae in Xiao-Chai-Hu-Tang which was commonly used to treat chronic hepatitis and liver fibrosis in China. The aim of this study was to assess whether chronic baicalein administration could prevent liver fibrosis induced by carbon tetrachloride (CCl(4)) in rats and investigate its possible protective mechanism. The antifibrotic effects of baicalein were assessed directly by hepatic histology and indirectly by measuring levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), hepatic hyaluronic acid, laminin and procollagen type III (PCIII) in serum, as well as hydroxyproline and matrix metalloproteinases (MMPs) in liver. In addition, we further investigated protein synthesis of platelet derived growth factor (PDGF) beta receptor which has been identified as attractive target for therapeutic intervention. CCl(4) treatment increased levels of AST, ALT, hyaluronic acid, laminin, and PCIII in serum, as well as hydroxyproline and MMPs in liver. Baicalein treatment (20, 40, or 80 mg/kg for 10 weeks) dose-dependently decreased levels of these markers. Baicalein also reduced inflammation, destruction of liver architecture, and collagen accumulation and significantly inhibited protein synthesis of PDGF-beta receptor. Together, our results suggest that chronic baicalein administration inhibits stellate cell activation and proliferation by the down-regulation of PDGF-beta receptor and prevents the development of CCl(4) induced liver fibrosis in rats.

Metabolites of scutellarein in rat plasma.

The metabolism of scutellarein was investigated in rats. Four metabolites (M1-M4) together with scutellarein were detected and identified as scutellarein-glucuronides in rat plasma by HPLC-DAD, HPLC-MS, and HPLC-MS/MS.