Comparative pharmacokinetic investigation on crocetin in hyperlipidemia and normal rats after oral administration.

Crocetin as one of the main components of saffron possesses a lot of pharmacological effects, especially the beneficial effects in the treatment of hyperlipidemia. However, the pharmacokinetics of crocetin in the pathological state of hyperlipidemia has not been reported. In present study, the pharmacokinetics of crocetin in hyperlipidemia rats after oral administration of crocetin was investigated and the possible mechanisms for the pharmacokinetics were explored. High-fat diet was used to induce hyperlipidemia in rats. The pharmacokinetics of crocetin was investigated in hyperlipidemia and normal rats after oral and intravenous administration of crocetin, and the possible mechanisms of the pharmacokinetic changes were investigated in terms of metabolism and absorption using in vitro incubation with liver microsomes and the everted gut sac method, respectively. Results indicated that the AUCs of crocetin in hyperlipidemia rats after oral administration of crocetin were remarkably decreased when compared with those in normal rats. Moreover, crocetin was also metabolized more rapidly in the liver microsomes of hyperlipidemia rats and intestinal absorption of crocetin was significantly reduced in hyperlipidemia rats. It suggested that the remarkably decreased AUCs of crocetin in hyperlipidemia rats might partly result from the result of faster metabolic elimination and reduced absorption of crocetin in the hyperlipidemia pathological state. And the present investigations conducted on rats demonstrate that further investigations into the kinetics of crocetin in humans with hyperlipidemia are necessary in order to ensure an adequate dosage in this indication.

Comparative investigation on the pharmacokinetics of geniposide in type 2 diabetic and normal rats after oral administration of Fructus Gradeniae extract.

Fructus Gradeniae, the fruit of Gardenia jasminoides Ellis, was used alone or in combination with other herb medicines in the treatment of type 2 diabetes mellitus in China for a long time. In present investigation, the HPLC method for the determination of geniposide in rat plasma was developed and validated, and the pharmacokinetics of geniposide in type 2 diabetic rats after oral administration of Fructus Gradeniae extract or pure was studied. The results showed that the pharmacokinetic profile (especially the area under the plasma concentration-time curve, AUC) of geniposide in type 2 diabetic rats after orally administered with Fructus Gradeniae extract or pure geniposide was remarkably different from that in normal rats. The results indicated that the increased AUC of geniposide in type 2 diabetic rats did not result from the effects of other components contained in Fructus Gradeniae. It could be speculated that the increased AUC of geniposide might result from the pathological state of type 2 diabetes mellitus which resulted in the pharmacokinetic alterations of geniposide.

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

ETHNOPHARMACOLOGICAL RELEVANCE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

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.

Antihyperglycemic effect of the traditional Chinese scutellaria-coptis herb couple and its main components in streptozotocin-induced diabetic rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Scutellaria-coptis herb couple (SC) is the main herb couple in many traditional Chinese compound formulas used for the treatment of diabetes mellitus, which has been used to treat diabetes mellitus for thousands of years in China. In this study we provide experimental evidence for the clinical use of SC in the treatment of diabetes mellitus. AIM OF THE STUDY: To confirm the anti-diabetic effect of SC extract and its main components, and to explore its mechanism from the effect on intestinal disaccharidases by in vivo and in vitro experiment. MATERIALS AND METHODS: SC extract was prepared and the main components (namely berberine and baicalin) contained in the extract were assayed with high performance liquid chromatography (HPLC). And diabetic model rats were induced by intraperitoneal injection of streptozotocin (STZ). After grouped randomly, diabetic rats were administered SC extract, berberine, baicalin, berberine+baicalin, acarbose and vehicle for 33d, respectively. Body weight, food intake, urine volume, urine sugars, fasting plasma glucose and fasting plasma insulin were monitored to evaluate the antidiabetic effects on diabetic rats. Intestinal mucosa homogenate was prepared and the activities of intestinal disaccharidases were assayed. Moreover, oral sucrose tolerance test (OSTT) was performed and the inhibitory effects of SC extract and its main components (berberine and baicalin) on the maltase and sucrase in vitro was evaluated. RESULTS: After the treatment of SC extract and its main components, the body weight and the fasting plasma insulin level were found to be increased while food intake, urine volume, urine sugars and fasting plasma were decreased. OSTT showed that SC extract and its main components could lower the postprandial plasma glucose level of diabetic rats. Furthermore, SC extract and its main components could inhibit the activities of intestinal disaccharidases in diabetic rats, whereas only SC extract and berberine could inhibit the activity of maltase in vitro. CONCLUSIONS: According to our present findings, scutellaria-coptis herb couple (SC) possessed potent anti-hyperglycemic effect on STZ-induced diabetic rats. And SC extract and its main components exerted anti-hyperglycemic effect partly via inhibiting the increased activities of intestinal disaccharidases and elevating the level of plasma insulin in diabetic rats induced by STZ.

Anti-hyperglycemic effects and mechanism of traditional Chinese medicine Huanglian Wan in streptozocin-induced diabetic rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Huanglian Wan (HLW) is a prescription of traditional Chinese medicine (TCM), which has been used to treat diabetes mellitus for thousands of years in China. In this study we provide experimental evidence for the clinical use of HLW in the treatment of diabetes mellitus. MATERIALS AND METHODS: HLW extract was prepared and the main components (namely berberine and catalpol) contained in the extract were assayed with high performance liquid chromatography (HPLC), and diabetic model rats were induced by intraperitoneal injection of streptozotocin (STZ). After grouped randomly, diabetic rats were administered low or high dose of HLW extract, acarbose and vehicle for 33 days, respectively. Body weight, food intake, urine volume, urine sugars, fasting plasma glucose and fasting plasma insulin were monitored to evaluate its antidiabetic effects in diabetic rats. Intestinal mucosa homogenate was prepared and the activities of intestinal disaccharidases were assayed. Moreover, oral sucrose tolerance test (OSTT) was performed and the inhibitory effect of HLW extract on the maltase and sucrase in vitro was evaluated. RESULTS: After the treatment of HLW extract, the body weight and the fasting plasma insulin level were found to be increased while food intake, urine volume, urine sugars and fasting plasma were decreased. OSTT showed that HLW extract could lower the postprandial plasma glucose level of diabetic rats. Furthermore, HLW extract could inhibit the activities of sucrase and maltase in vitro. CONCLUSIONS: According to our present findings, the TCM prescription HLW possessed potent anti-hyperglycemic effect on STZ-induced diabetic rats. And HLW extract exerted anti-hyperglycemic effect partly via inhibiting the increased activities of intestinal disaccharidases and elevating the level of plasma insulin in diabetic rats induced by streptozotocin.

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

Radix scutellariaewas used alone or in combinationwith othermedicinal herbs in the treatment oftype 2 diabetes mellitus in China. At present, the pharmacokinetics of baicalin in type 2 diabeticrats following oral administration of Radix scutellariae extract was investigated. The resultsshowed that the pharmacokinetics (especially AUC) of baicalin in type 2 diabetic rats after oraladministration of Radix scutellariae extract was remarkably different from that in normal rats.Then the mechanism which resulted in the increased AUC of baicalin in diabetic rats wasinvestigated from system clearance and presystemic metabolism. And it was found that theincreased AUC of baicalin in diabetic rats at least partly resulted from higher production ofbaicalein in the intestinal tract of type 2 diabetic rats.Moreover, the activity of ß-glucuronidase inintestinal mucosa of type 2 diabetic rats was demonstrated to be higher than that in normal rats,which confirmed the results above. In conclusion, the pharmacokinetic behavior of baicalin wassignificantly altered in type 2 diabetic rats after orally administrated Radix scutellariae extract,which may partly result from the increased activity of intestinal ß-glucuronidase under thepathological state of type 2 diabetes mellitus.

Polysaccharide from Gynura divaricata modulates the activities of intestinal disaccharidases in streptozotocin-induced diabetic rats.

During diabetes, structural and functional changes in the alimentary tract are known to take place resulting in an increased absorption of intestinal glucose and alterations in the activities of brush-border disaccharidases. To elucidate the effect of administrating polysaccharide from Gynura divaricata (PGD) on disaccharidase activities, the specific activities of intestinal disaccharidases, namely sucrase, maltase and lactase, were measured in streptozotocin-induced diabetic rats. Normal control and diabetic rats were treated by oral administration with PGD. Specific activities of intestinal disaccharidases were increased significantly during diabetes, and amelioration of the activities of sucrase and maltase during diabetes was clearly visible by the treatment with PGD. However, the increased activity of lactase during diabetes mellitus was remarkably alleviated by the administration of PGD only in the duodenum. Meanwhile, oral sucrose tolerance tests demonstrated that PGD alleviated the hyperglycaemia during diabetes mellitus, resulting from the amelioration in the activities of intestinal disaccharidases. The present investigation suggests that PGD exerted an anti-diabetic effect partly via inhibiting the increased intestinal disaccharidase activities of diabetic rats. This beneficial influence of administration of PGD on intestinal disaccharidases clearly indicates their helpful role in the management of diabetes.

Increased oral AUC of baicalin in streptozotocin-induced diabetic rats due to the increased activity of intestinal beta-glucuronidase.

The purpose of the study was to investigate the pharmacokinetics of baicalin, a major bioactive component of Scutellariae radix, in diabetic conditions. The 4-week diabetic rats were induced by intraperitoneal administration of streptozotocin. Plasma concentrations of baicalin were measured following oral (200 mg/kg) or intravenous (12 mg/kg) administration. Everted intestinal transport, intestinal mucosal metabolism of baicalin and intestinal beta-glucuronidase activity were also investigated. It was found that the diabetic condition significantly increased the exposure of baicalin following oral doses (AUC 100.77 +/- 4.16 microg x h/mL in diabetic rats vs. 48.48 +/- 7.94 microg x h/mL in normal rats). In contrast, the diabetic condition significantly decreased the exposure of baicalin following intravenous doses (AUC 11.20 +/- 2.28 microg x h/mL in diabetic rats vs. 18.02 +/- 3.45 microg x h/mL in normal rats). We also found lower apparent permeability coefficients of baicalin in the ileum of diabetic rats (8.43 x 10 (-6) +/- 2.40 x 10 (-6) cm/s in diabetic rats vs. 5.21 x 10 (-5) +/- 1.55 x 10 (-5) cm/s in normal rats). Further studies showed that the diabetic condition enhanced the hydrolysis of baicalin to baicalein in intestinal mucosal, accompanied by an increase of beta-glucuronidase activity. All these results suggested that the higher oral exposure of baicalin in diabetic rats did not result from the decreased hepatic metabolism or increased intestinal absorption of baicalin. The enhancement of intestinal beta-glucuronidase activity may partly account for the higher exposure of baicalin in diabetic rats after oral administration.

High-performance liquid chromatographic method for the determination and pharmacokinetic study of wogonoside in rat serum after oral administration of traditional Chinese medicinal preparation Huang-Lian-Jie-Du decoction.

A high-performance liquid chromatographic method for the determination of wogonoside in plasma of rats administrated orally with the traditional Chinese medicinal preparation Huang-Lian-Jie-Du decoction was developed. Sample preparation was carried out by protein precipitation with a mixture of acetonitrile and methanol (1:1, v/v). The extracted sample was separated on a Hypersil C(18) (150 x 5 mm i.d., 5 microm) analytical column by linear gradient elution using 0.05% (v/v) phosphoric acid (containing 5 mm sodium dihydrogen phosphate) and acetonitrile as mobile phase at a flow rate of 1.5 mL/min. The eluate was detected using a UV detector at 276 nm. The assay was linear over the range 0.109-7.0 microg/mL (R(2) = 0.9999, n = 5). Mean recovery was determined as 98.39%. Intra- and inter-day precisions (RSD) were < or =7.59%. The limit of quantitation was 0.109 microg/mL. After validation, the HPLC method developed was applied to investigate the preliminary pharmacokinetics of wogonoside in rat after oral administration of Huang-Lian-Jie-Du decoction.