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Ethnopharmacological Relevance: Luohanguo (LHG) extract major contenting mogrosides, as a nonnutritive sweetener, has been reported to exert a hypoglycemic effect on diabetic patients and animals. As the pharmacokinetics and pharmacodynamics of drugs were changed with diabetes, it may lead to the different pharmacological of mogrosides between diabetic and normal subjects., Aims of the Study: To characterise the pharmacokinetic profiles of mogrosides in T2DM rats., Study Design and Methods: High-fat diet and streptozocin induced type 2 diabetic mellitus rats were used to investigate the pharmacokinetic behavior of mogroside V and mogrosides IIIA 1 , IIA 1 , and IA 1 after T2DM rats orally administrated with mogroside V and 1-3 glucose residues' mogrosides, respectively. The validated convenient UPLC-QTOF/MS and UPLC-MS/MS methods were established to use in the pharmacokinetic studies of mogrosides in normal and T2DM rats. Additionally, the expression of the intestinal tight junction protein zonula occludens-1 (ZO-1) was also detected by immunohistochemical analysis, which assessed the function of passive intestinal permeability in T2DM rats., Results: The results showed that for rats treated with mogroside V, its metabolite mogroside IIIA 1 has a significant increase (p < 0.05) in maximum plasma concentration (C max , 163.80 ± 25.56 ng/mL) and area under the plasma concentration (AUC 0-t , 2327.44 ± 474.63 h·ng/mL) in T2DM rats compared with in normal rats. The mean residence time (MRT 0-t , 12.04 ± 0.97 h) of mogroside V showed a significant decrease (p < 0.05) in T2DM rats. However, the mogrosides IIIA 1 , IIA 1 and IA 1 showed no statistical differences in the normal and T2DM rats after administered with 1-3 glucose residues' mogrosides. Furthermore, the expression level of ZO-1 in the duodenum and colon of T2DM rats were downregulated., Conclusion: The pharmacokinetic profiles of mogroside V and its metabolite mogroside IIIA 1 in T2DM rats and normal rats showed some difference, it might be affected by the metabolic changes in the pathological state of T2DM., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: As one of the new drugs of traditional Chinese medicine, Sanye Tablet is employed as a hypolipidemic in the traditional medicine, but the biopharmaceutical properties of the drug is still unclear., Aim of the Study: Through the study of biopharmaceutical properties, the classical biopharmaceutics classification system (BCS) can be used to classify and predict the in vivo absorption properties. On this basis, the biopharmaceutical properties closely related to traditional Chinese medicine preparations are added and a modified BCS model is established to predict and judge the absorption degree of traditional Chinese medicine compound., Materials and Methods: Representative components of Sanye Tablet were selected and subjected to different in vitro tests. The experimental results were compared with the results of the BCS to evaluate the accuracy and applicability to Sanye Tablet. We take parameters of dissolution and stability based on product characteristics into account. A "modified-BCS" was developed and the results of the improved method and the classic method were compared. Also the ability of each classification system to predict and determine the extent of absorption of the Chinese herbal compound was investigated based on the absolute bioavailability of representative components., Results: For classic BCS, the five representative components (except for nuciferine) are all class III, nuciferine is class I/II obtained by Caco-2 cell assay and class III/IV obtained by everted gut sac assay. For modified BCS, paeoniflorin is class III, rutin, hyperoside and salvianolic acid B are class III/IV, and nuciferine is class I/II based on Caco-2 cell assay, class III/IV based on everted gut sac assay. Nuciferine is the best of the five components, with absolute bioavailability reaching 61.91% based on in vivo bioavailability test., Conclusions: The five representative components (except for nuciferine) are all class III/IV, which correlates well with the absolute bioavailability results and demonstrates that they are poorly absorbed substances. The correlation between the classification results obtained using the "modified-BCS" and absorption in the body is better than the correlation obtained using the classic method, suggesting that the improved BCS is more suitable for the characterization of Sanye Tablet. These results indicate that the oral formulation of Sanye Tablet is a BCS III/IV drug., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Dan-Lou tablet (DLT) is developed from the traditional Chinese medicine (TCM) formula Gualou Xiebai Baijiu Tang which has been used for at least 2000 years in China. DLT has been widely used in clinical practice to treat cardiovascular diseases., Aim of the Study: This study aimed to uncover the pharmacological mechanism of the compounds absorbed into the blood of Dan-Lou tablet (DLT) on coronary heart disease (CHD) using a network pharmacology integrated pharmacokinetics strategy., Materials and Methods: A rapid and sensitive method was developed for the simultaneous determination of the six compounds (puerarin, formononetin, calycosin, paeoniflorin, cryptotanshinone and tanshinone IIA) in rat plasma by liquid chromatography tandem mass spectrometry (LC-MS/MS). Then, the pharmacology network was established based on the relationship between five compounds absorbed into the blood targets (puerarin, formononetin, calycosin, cryptotanshinone and tanshinone IIA) and CHD targets., Results: The intra-and inter-day precision were less than 11% and the accuracy ranged from 88.2% to 112%, which demonstrated that the LC-MS/MS method could be used to evaluate the pharmacokinetic feature of the six compounds in rats after oral administration of DLT. The pathway enrichment analysis revealed that the significant bioprocess networks of DLT on CHD were positive regulation of estradiol secretion, negative regulation of transcription from RNA polymerase II promoter, lipopolysaccharide-mediated signaling pathway and cytokine activity., Conclusion: The proposed network pharmacology integrated pharmacokinetics strategy provides a combination method to explore the therapeutic mechanism of the compounds absorbed into the blood of multi-component drugs on a systematic level., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Da Chuan Xiong Decoction Compound preparation (DCXDCP) is a classic TCM formula of an aqueous extract made from Chuanxiong Rhizoma (Ligusticum chuanxiong Hort., umbelliferae) and Tianma Rhizoma (Gastrodia elata Bl., Orchidaceae). Gastrodin (GAS), a bioactive component of tianma, its pharmacokinetic (PK) behavior significantly changed after oral administration of DCXDCP compared with the extract of tianma. However, little is known about how the ingredients of chuanxiong influenced on the PK of GAS., Aim of the Study: To study the possible PK behavior differences of GAS after individually oral administration of tianma extract and tianma extract mixed with different active ingredients of chuanxiong to rats, as well as explore whether there were some herb-herb interactions., Materials and Methods: Different DCXDCP suspensions were prepared by mixing tianma extract with different active ingredients of chuanxiong. The rats were randomly assigned to six groups and were orally treated with different DCXDCP. At different predetermined time points after administration, the concentrations of GAS in the rat plasma were determined using HPLC, and the main PK parameters were investigated., Results: The results showed that tetramethylpyrazine had no significant effects on the PK parameters of GAS (p>0.05), whereas ferulic acid (FA), total phenolic acids and total alkaloids significantly increased AUC0-∞ (p<0.05). In general the observed changes in the PK parameters of GAS in DCXDCP could be closely related to the total phenolic acids and total alkaloids., Conclusion: It could be shown that total phenolic acids and total alkaloids present in Ligusticum chuanxiong in addition to other components not tested yet play an important role in affecting the PK of gastrodin in DCXDCP., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Ethnopharmacological Relevance: Gastrodia elata Blume, a traditional Chinese herb, was widely used against convulsant, vertigo, paralysis, epilepsy, tetanus, asthma and immune dysfunctions. Gastrodin is one of the major bioactive components of G. elata and it is known for its anticonvulsive, anti-inflammatory, antiepileptic and neuroprotective effects., Materials and Methods: An ultra high performance liquid chromatography-fluorescence detection (UHPLC-FLD) method was developed to determine gastrodin in rat plasma. Gastrodin and Thiamphenicol (internal standard, IS) were extracted from rat plasma by immediately protein precipitation. The pharmacokinetics of gastrodin in rats by following differently administered types was studies: intragastric administration of gastrodin (100mg/kg), parishin (116 mg/kg, with the same mole of gastrodin moiety) and G. elata extract (2.3g/kg, with the same mole of gastrodin moiety). Non-compartmental pharmacokinetic profiles were constructed using the software of WinNonlin (Phoenix, version 6.3), and the pharmacokinetic parameters were compared using unpaired Student's t-test., Results: The results showed that the pharmacokinetic parameters, including Cmax, Tmax, AUC0-∞, t1/2, MRT, Vd, CL, were quite different among the three types of gastrodin administration. The administration of parishin and G. elata extract, which either could convert to gastrodin in vivo or contained free gastrodin and abundant gastrodin conjugates, gave rise to higher elimination half-life (t1/2) and mean residence time (MRT) values for gastrodin compared to free gastrodin administered., Conclusion: The comparison of the pharmacokinetics of gastrodin among three different administered types of gastrodin in rats suggested that administration of parishin or G. elata extract in clinic may result in a longer duration time of action than that of the administration of free gastrodin. The results may provide some guidance for the clinical applications of parishin and G. elata., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Ethnopharmacological Relevance: Zeng-Sheng-Ping (ZSP), also called antitumor B, is a marketed Chinese traditional medicine used for cancer prevention., Aim of the Study: Currently, for the quality control of Chinese traditional medicines, marker compounds are not selected based on bioactivities and pharmaceutical behaviors in most of the cases. Therefore, even if the "quality" of the medicine is controlled, the pharmacological effect could still be inconsistent. The aim of this study is to establish an activity and absorption-based platform to select marker compound(s) for the quality control of Chinese traditional medicines., Materials and Methods: We used ZSP as a reference Chinese traditional medicine to establish the platform. Activity guided fractionation approach was used to purify the major components from ZSP. NMR and MS spectra were used to elucidate the structure of the isolated compounds. MTT assay against oral carcinoma cell line (SCC2095) was performed to evaluate the activities. UPLC-MS/MS was used to quantify the pure compounds in ZSP and the active fraction. The permeabilities of the identified compounds were evaluated in the Caco-2 cell culture model. The intracellular accumulation of the isolated compounds was evaluated in the SCC2095 cells., Results: The major compounds were identified from ZSP. The contents, anti-proliferation activities, permeabilities, and intracellular accumulations of these compounds were also evaluated. The structure of these purified compounds were identified by comparing the NMR and MS data with those of references as rutaevine (1), limonin (2), evodol (3), obacunone (4), fraxinellone (5), dictamnine (6), maackiain (7), trifolirhizin (8), and matrine (9). The IC50 of compounds 5, 6, and 7 against SCC2095 cells were significantly lower than that of ZSP. The uptake permeability of compounds 5, 6, and 7 were 2.58 ± 0.3 × 10(-5), 4.33 ± 0.5 × 10(-5), and 4.27 ± 0.8 × 10(-5) respectively in the Caco-2 cell culture model. The intracellular concentrations of these compounds showed that compounds 5, 6, and 7 were significantly accumulated inside the cells., Conclusion: Based on the activity against oral carcinoma cell line as well as the absorption permeability, compound 5, 6, and 7 are selected as quality control markers for ZSP. An activity and absorption-based platform was established and successfully used for the quality control of ZSP., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

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., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Ethnopharmacological Relevance: Glycyrrhizae uralenis (GU) is often prescribed together with Cortex daphnes (CD) in traditional Chinese medicinal practice to increase the efficacy of CD on the treatment of rheumatoid arthritis (RA), but the reasons were still unknown. In order to clarify the rationality of herbaceous compatibility between CD and GU, the comparative evaluations on pharmacokinetic behaviors of daphnetin (a predominantly active ingredient in CD) after intragastric administration of CD and CD-GU (combination of CD and GU) extract were studied. In addition, the effects of glycyrrhizin and liquiritin, active ingredients of Glycyrrhiza triterpenes and Glycyrrhiza flavones respectively, on the pharmacokinetics of daphnetin were also investigated., Materials and Methods: Five groups of rats were orally administered with CD extract, CD-GU extract, pure daphnetin, co-administration of daphnetin and glycyrrhizin as well as co-administration of daphnetin and liquiritin at the same single dose of daphnetin (20 mg/kg). The rat plasma concentrations of daphnetin were determined by our developed UPLC-MS/MS method. The pharmacokinetics of daphnetin in above groups were investigated and compared., Results: Comparing with oral administration of CD extract, AUC and Tmax of daphnetin significantly increased after giving CD-GU (p<0.05). In addition, in comparison to daphnetin alone, co-administration of daphnetin with liquiritin significantly increased the AUC and Cmax of daphnetin for ~1.5-fold, while co-administered with glycyrrhizin showed limited impact on the pharmacokinetics of daphnetin., Conclusions: In this study, it was found that liquiritin, one of the major components of GU, significantly enhanced the bioavailability of the main component daphnetin in CD. In addition, the bioavailability of daphnetin in the CD-GU prescription was also significantly higher than that in CD alone, which could be due to liquiritin. Such results explained the mechanism of the increased efficacy in treating RA with the combined use of CD and GU., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Ethnopharmacological Relevance: Shaoyao-Gancao Decoction (SGD), a well-known traditional Chinese medicine prescription, is a combination of Radix Paeoniae Alba (Paeonia lactiflora Pall, root) and Glycyrrhizae uralensis (Glycyrrhiza uralensis Fisch., root and rhizome, honeyed) for spasmolysis and emergency pain relief. Paeoniflorin (PF) and glycyrrhetinic acid (GA) are two typical active components of SGD for pain relief., Aim of the Study: To study comparative pharmacokinetics of ten bioactive compounds in SGDs with two different combinations of RP and GU, and therefore to investigate the herb-herb interaction mechanisms of Shaoyao-Gancao Decoction for better spasmolysis and emergency pain relief in rats., Materials and Methods: Herbal IR macro-fingerprinting was implemented to provide the full chemical fingerprints of RP, GU and SGD decoctions and to investigate the variation rule of the full chemical profile of SGDs with various combinations of RP and GU. A specifically developed HPLC-MS/MS assay coupled with protein precipitation method was employed to determine the plasma concentrations of the ten analytes. Male Wistar rats were orally administered with SGD1 (RP:GU, 1:1 (w/w)) and SGD2 ((RP:GU, 4:1 (w/w)) equivalent to 9.5 g/kg body weight of GU., Results: Full chemical fingerprints of RP, GU and SGDs with various combinations of RP and GU were provided in the form of IR macro-fingerprints. Except for liquiritin, there were statistically significant differences (p<0.05 or p<0.01) of these analytes between SGD1 and SGD2 in in vivo pharmacokinetic study. Compared with the results when oral administrated with SGD1, six glycosides (PF, albiflorin, oxypaeoniflorin, isoliquiritin, ononin, and glycyrrhizin) exhibited higher systematic exposure levels (AUC0-t) and slower elimination rates (CL) whereas two glycones (GA and isoliquiritigenin) were the reverse when administrated with SGD2., Conclusions: Increasing the amount of RP attenuated the inhibitory effect of GA via competing being consumed by intestinal bacteria (or β-glucosidase) to reduce the conversion amount of glycyrrhizin to GA and subsequently to afford significantly higher bioavailability and longer efficacy of PF, glycyrrhizin, albiflorin, oxypaeoniflorin, isoliquiritin, and ononin, leading to better spasmolysis and emergency pain relief., (© 2013 Elsevier Ireland Ltd. All rights reserved.)

Ethnopharmacological Relevance: Samul-tang (Si-Wu-tang in Chinese, Shimotsu-to in Japanese), widely used in eastern Asia, is composed of Angelica gigas (Angelicae Gigantis Radix), Cnidium officinale (Cnidii Rhizoma), Paeonia lactiflora (Paeonia Radix) and Rehmannia glutinosa (Rehmanniae Radix Preparata). Paeoniflorin, one of active components in Samul-tang has anti-platelet, anti-inflammation, anti-cancer and neuroprotective properties. However, there is no information about the effects of gender and food intake on the pharmacokinetics of paeoniflorin till now., Aim of the Study: This study was conducted to investigate whether food and gender could influence pharmacokinetic profiles of paeoniflorin after oral administration of Samul-tang., Materials and Methods: Male and female rats were administered with a single oral dose of Samul-tang equivalent to 80 mg/kg of paeoniflorin. Plasma concentrations of paeoniflorin were measured by high-performance liquid chromatography. The statistical differences of each group were evaluated using the analysis of variance (ANOVA) or Student t-test., Results: The pharmacokinetic parameters of paeoniflorin were not significant different by gender difference. However, the maximum plasma concentration (C(max), 0.47±0.29 μg/mL versus 1.10±0.35 μg/mL), area under the concentration-time curve (AUC(0→∞), 1.41±0.89 h · μg/mL versus 3.12±1.61 h · μg/mL) and relative bioavailability (F(rel)=2.21) of fed rats were significantly increased in comparison with those of fasted rats (P<0.05)., Conclusion: Taken together, food intake can affect both the rate and extent of absorption of paeoniflorin when Samul-tang was administered orally. Furthermore, this study demonstrates a readily preparative HPLC method in the research of traditional herbal medicine., (Copyright © 2012. Published by Elsevier Ireland Ltd.)

Natural plant compounds have an unexceptional influence in pharmacy as they provide an uncountable number of invaluable lead molecules. Phytochemical researches nowadays focus on bio-assay guided revealing of the therapeutic profile and synergism of medicinal herbs and their constituents. Assessing the clinical and biological potential and determining the pharmacokinetics of herbal constituents is also an area of much interest. This work was conducted in order to carry out a sensitive liquid chromatography tandem mass spectrum (HPLC-MS/MS) method for the pharmacokinetics study of (+)-pinoresinol-di-β-D-glucopyranoside (PG) in rats' plasma after oral administration of Eucommia ulmoides Oliv extract. The validated method was by means of linearity, precision, matrix effect and recovery so that it could be used for the pharmacokinetic study of PG. The obtained pharmacokinetic parameters shown that PG pertains to one-compartment model and 95% of PG was eliminated within 12h., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Ethnopharmacological Relevance: Da Chuan Xiong Decoction Compound preparation (DCXDCP), the formulation of a classical Chinese prescription recorded in "Xuanminglunfang", was clinically employed to treat migraine's disease., Aim of the Study: In order to investigate the influence of compatibility on the pharmacokinetics of the active ingredient gastrodin (GAS), the comparative evaluations on pharmacokinetics of DCXDCP with various combinations of its constituent herbs in plasma after oral administration were studied., Materials and Methods: The rats were randomly assigned to four groups and orally administered with different prescription proportion of Gastrodia elata Bl. and Ligusticum chuanxiong Hort. (1:0; 1:0.25; 1:2.1; 1:4.2), respectively. At different predetermined time points after administration, the concentrations of GAS in rat plasma were determined by using HPLC, and main pharmacokinetic parameters were investigated., Results: The results showed that the pharmacokinetic parameters, AUC and C(max) of GAS were dramatically different (p<0.05) after oral administration of G. elata Bl. and the different combinations of its constituent herbs., Conclusions: These indicated that the compatibility effects of other ingredients present in DCXDCP could affect the pharmacokinetics of the prescription., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Ethnopharmacological Relevance: Polygonum multiflorum is an important traditional Chinese medicine used for health promotion and disease treatment. One major bioactive compound in P. multiflorum is a stilbene glycoside (2,3,5,4'-tetrahydroxystilbene-2-O-β-d-glucoside, PM-SG), which possesses antioxidative, anti-inflammatory and endothelial-protective activities., Materials and Methods: The purpose of the present study was to investigate in vivo pharmacokinetics and tissue distribution of PM-SG after oral administration of Polygonum multiflorum extract to rats by using a reversed-phase high-performance liquid chromatography coupled with liquid-liquid phase extraction. The pharmacokinetic parameters were determined using both compartmental and non-compartmental analyses., Results: All calibration curves for PM-SG in rat plasma and tissues were linear (all r(2)>0.99) over the range of 0.27-185.00 μg/ml. The intra- and inter-day variations were less than 3% at concentration range of 8.7-131.2 μg/ml and good overall recoveries (97.7-101.5%) were obtained at the same range. The maximum concentration (C(max)) and the time to reach this concentration (T(max)) of PM-SG were 31.9 μg/ml and 40.0 min, respectively. The pharmacokinetic profiles estimated by fitting two-compartment and non-compartment models revealed that PM-SG was rapidly absorbed into the body fluids and widely distributed throughout the body, with great efficiency of utility, followed by quick elimination. The highest PM-SG levels were detected in liver and lungs (90.3 ± 20.8 μg/g and 86.8 ± 9.0 μg/g, respectively) whereas little in brain and testes, indicating PM-SG can hardly penetrate the blood-brain and blood-testicle barriers., Conclusions: This was the first report on the favorable pharmacokinetic profiles of PM-SG in rat plasma and tissues after oral administration. It may provide a meaningful basis for clinical application of such a bioactive compound of herbal medicines., (Crown Copyright © 2011. Published by Elsevier Ireland Ltd. All rights reserved.)

Aim of the Study: To establish a HPLC-MS method and investigate the pharmacokinetic properties of paeoniflorin, albiflorin and oxypaeoniflorin and the pharmacokinetics difference of Radix Paeoniae Rubra and Radix Paeoniae Alba., Materials and Methods: The extracts of Radix Paeoniae Rubra and Radix Paeoniae Alba were separately administrated to rats. The concentrations of paeoniflorin, albiflorin and oxypaeoniflorin in rat plasma were determined by HPLC-ESI-MS method. The plasma samples were pretreated by protein precipitation with methanol and chromatographic separation was performed on a C(18) column with a mobile phase consisted of 0.1% formic acid and methanol (67:33, v/v). The detection was accomplished by multiple-reaction monitoring (MRM) scanning via electrospray ionization (ESI) source operating in the negative ionization mode. Main pharmacokinetic parameters were estimated and the total AUC of the three components were compared., Results: The pharmacokinetic parameters of paeoniflorin, albiflorin and oxypaeoniflorin were significantly different. There was significant difference between the pharmacokinetic characteristics of Radix Paeoniae Rubra and Radix Paeoniae Alba., Conclusions: A specific and sensitive HPLC-ESI-MS method was developed for simultaneous determination of paeoniflorin, albiflorin and oxypaeoniflorin in rat plasma and was successfully applied to pharmacokinetic study. The results might be helpful for the investigation of different effects of Radix Paeoniae Rubra and Radix Paeoniae Alba., (Copyright 2010 Elsevier Ireland Ltd. All rights reserved.)

Aim: White peony root and sulfur fumigated white peony root are produced by different processing methods from the root of Paeonia lactiflora Pall, but the two traditional Chinese medicines are used under the same common name white peony root. In order to clarify the influence of sulfur fumigation on pharmacokinetics of the main monoterpene glucoside components in white peony root, an investigation was carried out to compare the pharmacokinetics of sodium paeoniflorin sulfonate (1) and paeoniflorin (2), benzoylpaeoniflorin sulfonate (3) and benzoylpaeoniflorin (4), as well as 1 in sulfur fumigated white peony root extract (SWPE) and 2 in white peony root extract (WPE)., Materials and Methods: A high-performance liquid chromatographic (HPLC) assay was developed to determine the plasma concentrations of the four analytes. Kunming species of mice were orally administered the four compounds and the two extracts with approximately the same dose., Results: It was found that C(max) and AUC of 1 and 3 were increased (P<0.05), and the T(max) and t(1/2) were prolonged (P<0.05) by comparison with that of 2. Similar results were also observed for the pharmacokinetics parameters of 1 in SWPE and 2 in WPE. However, benzoylpaeoniflorin (4) was not detected in plasma collected at certain intervals after administered orally to mice., Conclusions: These results indicate that sulfonation of the monoterpene components could improve the bioavailability and delay the absorption of them in mice., (Copyright 2010 Elsevier Ireland Ltd. All rights reserved.)

Shuang-Dan (SD) is a traditional Chinese prescription containing Cortex Moutan and Radix Salviae miltiorrhizae and commonly used for treating cardiovascular disease. Paeoniflorin is a main effective ingredient of Cortex Moutan and the pharmacokinetic differences of paeoniflorin following oral administration of pure paeoniflorin, Cortex Moutan extract and SD decoction to rats were studied with approximately the same dose of 30mg/kg paeoniflorin. At different time points (5, 10, 15, 30, 45, 60, 90, 120, 150, 210, 270, 360, 450min), plasma concentration of paeoniflorin was determined using a simple and rapid HPLC-MS method. Unpaired student's t-test was used for the statistical comparison. A bimodal phenomenon was observed in the plasma profile after oral administration of Cortex Moutan extract. Statistically significant increase (P<0.05) in pharmacokinetic parameters of paeoniflorin including AUC(0-t), AUC(0-infinity) and MRT were obtained after oral administration of Cortex Moutan or SD decoction comparing with pure paeoniflorin. The investigation showed that among all calculated parameters, AUC(0-t), AUC(0-infinity), MRT, k(e) and T(1/2), there were no significant differences between the two decoctions. The results indicated that the reason which delay the elimination of paeoniflorin and enhance its bioavailability might be some ingredients in Cortex Moutan extract.

An investigation was designed and conducted to compare the pharmacokinetics difference of paeoniflorin after oral administration of the extracts of Radix Paeoniae Rubra and Radix Paeoniae Alba to rats on separate occasions. Quantification of paeoniflorin in rat plasma was achieved using a simple and rapid HPLC method for pharmacokinetic study. After oral administration of decoctions of Radix Paeoniae Rubra and Radix Paeoniae Alba, paeoniflorin was absorbed and reached a maximum concentration of 3.69+/-1.46 and 1.46+/-0.29 (p<0.05)microg/ml at 1.67+/-0.43 and 0.80+/-0.35 h (p<0.05), respectively. Compared to the AUC (18.85+/-7.54 microg h/ml) after oral administration of the paeoniflorin solution, a smaller AUC (10.61+/-1.51 microg h/ml, p<0.05) and a larger AUC (24.89+/-7.41 microg h/ml) of paeoniflorin after oral administration of the decoctions of Radix Paeoniae Alba and Radix Paeoniae Rubra were obtained, respectively. There were statistically significant differences in pharmacokinetic parameters of paeoniflorin including the t(max), C(max), AUC, t(1/2), CL, and V(d) among the animals orally administered the decoctions of Radix Paeoniae Rubra and Radix Paeoniae Alba. In particular, the parameters of t(max), C(max), and AUC of paeoniflorin were remarkably increased (P<0.05, P<0.001) when oral administering paeoniflorin in the decoctions of Radix Paeoniae Rubra, but t(1/2), V(d), and CL were decreased (P<0.05 or P<0.01), in comparison of the decoction of Radix Paeoniae Alba.

Huang-Lian-Jie-Du-Tang (HLJDT) is an important "heat-clearing" multiherb remedy of traditional Chinese medicine, and Radix scutellariae (Scutellaria baicalensis Georgi, Labiatae) is a key ingredient herb in it. Baicalin and wogonoside are two main effective ingredients enriched in Radix scutellariae. In the present study, pharmacokinetic differences of baicalin following oral administration of pure baicalin, Radix scutellariae extract, baicalin co-administrated with extract of the other three herbs of HLJDT and HLJDT were investigated in male S.D. rats with approximately the same dose of 200 mg/kg baicalin. The pharmacokinetic comparison of wogonoside was conducted only in Radix scutellariae extract and HLJDT. Plasma concentrations of baicalin and wogonoside were determined using HPLC method. Unpaired Student's t-test was used for statistical comparison. The results indicated that baicalin and wogonoside demonstrated bimodal phenomenon in the plasma profile. Some ingredients in the other three herbs of HLJDT, not in Radix scutellariae itself, had pharmacokinetic interaction with baicalin and wogonoside and hence decreased their systematic exposure level (p<0.01). The absorption site of baicalin was preliminary evaluated in rat using in situ absorption in stomach and different intestinal segments and results revealed the existence of double-site absorption of baicalin. The first absorption site was in upper intestinal, probably via directly absorption of baicalin; while the second absorption site was in colon in the form of aglygon.

We carried out three experimental trials to determine antidiabetic effects of Aloe arborescens Miller components. Firstly, ICR mice which received frequent injections of streptozotocin (Sz) in small doses (low-dose Sz-induced diabetes mice) were fed ad libitum with basal diets supplemented with components of Aloe arborescens Miller var. natalensis Berger (Kidachi aloe) and Aloe vera Linne from 31 days before to 73 days after the Sz injections. Variation in blood glucose levels, incidence rates of insulitis and blood insulin levels were examined during the trial. As a result, groups receiving diets supplemented at the rate of 2% with whole leaf of Kidachi aloe and 10 KDa fraction powder (a fraction with less than 10 KDa molecular weight derived from Kidachi aloe leaf skin juice by ultra filtration) significantly suppressed the elevation of blood sugar as compared to a control group receiving basal diet. In contrast, there was no significant effect with Aloe vera leaf pulp powder. Insulitis emerged at the rate of 87% in the basal diet group. On the contrary, the whole aloe leaf and 10 KDa fraction groups significantly decreased the incidence of insulitis and incidence rates of whole aloe leaf and 10 KDa fraction powder were 51 and 38%, respectively. While insulin levels in the basal diet group averaged at 0.05 ng, more than four times the insulin level was observed in the 10 KDa group relative to the basal diet group. Secondary, the inhibitory effects of test materials on intestinal glucose absorption were observed using the jejunum of rats. A strong inhibitory action on intestinal glucose absorption was observed in the 10 KDa fraction powder group. Thirdly, phenol compounds derived from aloe in the blood serum and organs were quantitatively measured by a HPLC following forced administration of aloe components to rats to determine absorption kinetics of aloe components inside the body. The primary component of aloe phenol compounds is the same component of the 10 KDa fraction powder and it was found in the pancreas and liver in addition to in the blood serum. The above results indicate that fore and aft when Sz injections could cause selective toxicity to B cells of islets, the dietary administration of 10 KDa fraction powder to mice would lead to the persistence of aloe phenol compound having an antioxidant activity in the pancreas and blood, which could protect islets of Langerhans from the destruction caused by methyl radical derived from Sz. The results also suggested the possibility of the 10 KDa fraction powder to alleviate the burden of insulin secretion as it has an inhibitory action on glucose absorption in the jejunum of rats.

Paeonia lactiflora Pall. (Ranunculaceae) root and Sinomenium acutum Rehder and Wilson (Menispermaceae) stem are two herbs widely used in Chinese medicine to treat rheumatoid arthritis. While, in theory, either herb could be used alone, in practice, Chinese medicine practitioners prescribe them together. Studies on pharmacokinetic interaction between the active constituents of these two herbs (paeoniflorin and sinomenine, respectively) provide empirical evidence to support their clinical practice. A single dose of paeoniflorin (150 mg/kg) alone and with sinomenine hydrochloride (90 mg/kg) was administered by gastric gavage to unrestrained conscious male Sprague-Dawley rats (n=5 or 6, 240-270 [corrected] g). Blood samples were collected periodically via a jugular vein before and after dosing from 10 min to 12 h. A high-performance liquid chromatographic (HPLC) assay was developed to determine the plasma concentrations of paeoniflorin. Non-compartmental pharmacokinetic profiles were constructed by using the software PK Solutions 2.0. The pharmacokinetic parameters were compared using unpaired Student t-test. After co-administration of sinomenine, the peak plasma concentration of paeoniflorin was elevated (P<0.01), the peak time was delayed (P<0.01), the AUC(0-t) was increased (P<0.001), the mean residence time (MRT) was prolonged (P<0.01), the C(L) was decreased (P<0.01) and the V(d) was reduced (P<0.05). These results indicate that sinomenine hydrochloride at 90 mg/kg significantly improved the bioavailability of paeoniflorin in rats.

The objective of the present study was to investigate the effects of cerebral ischemia-reperfusion on pharmacokinetics of paeoniflorin after intravenous administration of Paeoniae Radix extract (PRE) in rats. The cerebral ischemia-reperfusion rats were induced by occluding the bilateral carotid arteries of normal rats for 2 h, followed by reperfusion. The resultant animals were immediately administrated by PRE (at a dose of 60 mg/kg of paeoniflorin) via the femoral vein, whilst the same dose was injected to the normal rats. Plasma samples were collected at different time to construct pharmacokinetic profiles by plotting drug concentration versus time. Quantification of paeoniflorin in rat plasma was achieved by using a simple and rapid high-performance liquid chromatographic method. In normal rats, the major parameters of distribution half-life (t1/2alpha), elimination half-life (t1/2beta), area under the plasma concentration-time (AUC), mean retention time (MRT), and clearance (CL), estimated by an open two-compartmental model, were 0.69, 18.77 min, 5338.71 (microg min)/ml, 18.13 min and 0.0162 mg/(kg min), respectively. However, in ischemia-reperfusion rats, the corresponding parameters were 2.04, 24.51 min, 9626.00 (microg min)/ml, 29.75 min and 0.0071 mg/(kg min), respectively. The results showed that ischemia- reperfusion significantly increased AUC values, decreased CL values, and prolonged the terminal half-life of paeoniflorin. These findings suggest that the injuries of ischemia-reperfusion could play an important role in pharmacokinetic process of paeoniflorin.

The leaves of Eremophila gilesii have been used traditionally to treat colds, headaches, sores, and chest pains. Our previous screening of Australian native plants showed that the methanol extract of the aerial parts of E. gilesii demonstrated notable inhibition of ADP-induced human platelet aggregation and serotonin release. Subsequent fractionation on the methanol extract led to the isolation of two phenylethanoid glycosides, verbascoside (1) and poliumoside (2). This is the first study reporting the presence of phenylethanoid glycosides in E. gilesii.