Comparative pharmacokinetic investigation on baicalin and wogonoside in type 2 diabetic and normal rats after oral administration of traditional Chinese medicine Huanglian Jiedu decoction.

Huanglian Jiedu decoction (HLJDD) is used traditionally in China for the treatment of diabetes mellitus in clinical practice, which has been proved to be effective. The purpose of this study was to investigate the pharmacokinetic characteristics (especially the area under the curve, AUC) of baicalin and wogonoside in type 2 diabetic rats after oral administration of HLJDD extract and to explore its possible mechanism. HLJDD extract and Radix scutellariae extract were prepared and the contents of baicalin and wogonoside contained in two extracts were assayed with high performance liquid chromatography (HPLC). Type 2 diabetic rats were induced by high fat diet and intraperitoneal injection of streptozotocin. Pharmacokinetics of baicalin and wogonoside in type 2 diabetic and normal control rats after oral administration of HLJDD extract or Radix scutellariae extract were investigated. Pharmacokinetics of baicalin in type 2 diabetic and normal rats after oral administration of pure baicalin was also investigated. The pharmacokinetic parameters (especially AUCs) of baicalin and wogonoside in type 2 diabetic rats after oral administration of HLJDD extract were remarkably different from those in normal rats. And the alterations of the AUCs of baicalin and wogonoside in type 2 diabetic rats after oral administration of Radix scutellariae extract were similar to those after oral administration of HLJDD extract. Moreover, the increase of the AUC of baicalin in type 2 diabetic rats after oral administration of pure baicalin was similar to that after oral administration of HLJDD extract or Radix scutellariae extract. The pharmacokinetic behaviors of baicalin and wogonoside (especially the systemic exposure [AUCs] of baicalin and wogonoside) were significantly altered in type 2 diabetic rats after orally administrated HLJDD extract. And the increased AUCs of baicalin and wogonoside in type 2 diabetic rats after oral administration of HLJDD extract resulted from neither the effects of other herbs contained in HLJDD nor the effects of other components contained in Radix scutellariae. It might result from the effects of the pathological status of type 2 diabetes mellitus.

He MY ，Deng YX ，Shi QZ ，Zhang XJ ，Lv Y ... -  《-》

Comparative pharmacokinetics of baicalin after oral administration of pure baicalin, Radix scutellariae extract and Huang-Lian-Jie-Du-Tang to rats.

Lu T ，Song J ，Huang F ，Deng Y ，Xie L ，Wang G ，Liu X ... -  《JOURNAL OF ETHNOPHARMACOLOGY》

Comparative pharmacokinetics of baicalin and wogonoside by liquid chromatography-mass spectrometry after oral administration of Xiaochaihu Tang and Radix scutellariae extract to rats.

The aim of this study was to compare the pharmacokinetics of baicalin and wogonoside in rats following oral administration of Xiaochaihu Tang (Minor Radix Bupleuri Decoction) and Radix scutellariae extract. Thus, a specific LC-MS method was developed and validated for the determination of these flavonoids in the plasma of rats after oral administration Xiaochaihu Tang and Radix scutellariae extract. Chromatographic separation was performed on a Zorbax SB C(18) column (150mmx4.6mm, i.d.: 5microm) with 0.1% formic acid in water and acetonitrile by linear gradient elution. Baicalin, wogonoside and carbamazepine (internal standard, I.S.) were detected in select-ion-monitoring (SIM) mode with a positive electrospray ionization (ESI) interface. The following ions: m/z 447 for baicalin, m/z 461 for wogonoside and m/z 237 for the I.S. were used for quantitative determination. The calibration curves were linear over the concentration ranges from 0.1231 to 6.156microg mL(-1) for baicalin and 0.08832 to 4.416microg mL(-1) for wogonoside. The lower limit of detection (LLOD) based on a signal-to-noise ratio of 2 was 0.06155microg mL(-1) for baicalin and 0.04416microg mL(-1) for wogonoside. Intra-day and inter-day precisions (RSD%) were within 10% and accuracy (RE%) ranged from -6.4 to 4.4%. The extraction recovery at three QC concentrations ranged from 74.7 to 86.0% for baicalin and from 71.3 to 83.7% for wogonoside. The plasma concentrations of baicalin and wogonoside in rats at designated time periods after oral administration were successfully determined using the validated method, pharmacokinetic parameters were estimated by a non-compartment model. Following oral administration of Xiaochaihu Tang and Radix scutellariae extract, the t(1/2) of baicalin was 3.60+/-0.90 and 5.64+/-1.67, the C(max1) was 1.64+/-0.99 and 5.66+/-2.02, the t(max1) was 0.13+/-0.05 and 0.20+/-0.07, the C(max2) was 2.43+/-0.46 and 3.18+/-1.66, and the t(max2) were 6.40+/-1.67 and 5.66+/-2.02, respectively. Following oral administration of Xiaochaihu Tang and Radix scutellariae extract, the t(1/2) of wogonoside was 4.97+/-1.68 and 7.71+/-1.55, the C(max1) was 1.39+/-0.83 and 1.45+/-0.37, the t(max1) was 0.21+/-0.20 and 0.17+/-0.01, the C(max2) was 1.90+/-0.55 and 1.42+/-0.70, and the t(max2) was 5.60+/-1.67 and 5.20+/-1.79, respectively. A significant difference (p<0.05) was observed for t(1/2), and the elimination of baicalin and wogonoside in Xiaochaihu Tang was increased.

Zhu Z ，Zhao L ，Liu X ，Chen J ，Zhang H ，Zhang G ，Chai Y ... -  《-》

Hypolipidemic effect of the Chinese polyherbal Huanglian Jiedu decoction in type 2 diabetic rats and its possible mechanism.

Huanglian Jiedu Decoction (HLJDD) is used traditionally in China for the treatment of diabetes mellitus in clinical practice, which has been proved to be effective. In present investigation, the 3D-HPLC fingerprint of HLJDD and the contents of main components (namely berberine, baicalin and geniposide) contained in the extract of HLJDD were assayed with high performance liquid chromatography (HPLC). Type 2 diabetic rats were induced by high fat diet and streptozotocin. Type 2 diabetic rats were treated with HLJDD extract for 30d, while blood glucose and body weight were monitored during the experiment. At the end of experiment, the levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) were assayed. Intestinal mucosa homogenate was prepared and the activity of pancreatic lipase was analyzed. Moreover, the olive oil loading test (OOLT) was performed and the inhibitory effect of HLJDD extract on the pancreatic lipase in vitro was evaluated. The results showed that, after the treatment of HLJDD extract, the final body weight and the levels of fasting plasma glucose, TC, TG and LDL-C were significantly reduced while the HDL-C level was increased in type 2 diabetic rats. The OOLT showed that HLJDD extract could lower the postprandial plasma TG level of type 2 diabetic rats. The activity of pancreatic lipase in type 2 diabetic rats was decreased after the treatment of HLJDD extract. Moreover, HLJDD extract could inhibit the activity of pancreatic lipase in vitro. In conclusion, the TCM prescription HLJDD possessed potent lipid-modulating effect on type 2 diabetic rats. And HLJDD extract exerted hypolipidemic effects partly via inhibiting the increased activity of intestinal pancreatic lipase in type 2 diabetic rats.

Zhang XJ ，Deng YX ，Shi QZ ，He MY ，Chen B ，Qiu XM ... -  《-》

Comparative pharmacokinetics of baicalin in normal and the type 2 diabetic rats after oral administration of the Radix scutellariae extract.

Deng YX ，Shi QZ ，Chen B ，Zhang XJ ，Liu SZ ，Qiu XM ... -  《-》