Development of an ultra-high-performance liquid chromatography coupled with triple quadrupole mass spectrometry method for comparative pharmacokinetics of six triterpenoids in rat plasma and application to different forms of Phytolacca acinosa.

Phytolacca acinosa is an herb for treatment of ascites and tumor. Two forms of P. acinosa, i.e. raw and vinegar-processed herb, have been used in clinic. However, pharmacokinetic difference between the two forms of P. acinosa has not been fully understood. Herein, a comparative pharmacokinetic method based on liquid chromatography with tandem mass spectrometry was developed for quantification of six bioactive triterpenoids, including esculentoside H, esculentoside T, esculentoside A, esculentoside B, phytolaccagenic acid, and phytolaccagenin in rat plasma after oral administration of different forms of P. acinosa. Separation was performed on an Acquity BEH C18 column (1.7 µm, 2.1 mm × 50 mm). The method was validated over a linear range of 2.0-5000 ng/mL. Intraday and interday bias were within ±5%. Besides, all triterpenoids were stable in plasma during different storage conditions. The described method was successfully applied to a comparative pharmacokinetic study of raw and vinegar-processed P. acinosa in rats. Notably, double peak phenomenon for six triterpenoids of P. acinosa was observed for the first time. AUC0→t and Cmax values of esculentoside H, esculentoside T, phytolaccagenic acid, and phytolaccagenin were significantly lower in vinegar-processed group than that of raw group, indicating the oral bioavailability of the four triterpenoids was decreased after vinegar processing.

A sensitive UPLC-MS/MS method for simultaneous determination of polyphenols in rat plasma: Application to a pharmacokinetic study of dispensing granules and standard decoction of Cinnamomum cassia twigs.

This study established a rapid and reliable approach using liquid chromatography-tandem mass spectrometry for the simultaneous determination of cinnamic acid, vanillic acid and protocatechuic acid in rat plasma. This is the first report on a comparative pharmacokinetic study of dispensing granules and standard decoction of Cinnamomum cassia twigs in rats. After liquid-liquid extraction by ethyl acetate, the plasma samples were subjected to LC-MS/MS for multiple reaction monitoring. The standard curves showed good linear regression (r2 > 0.9991) in the range of 10.0-16000 ng/mL. The intra- and inter-day accuracy and precision were found to be within 15% of the nominal concentration. The recoveries of the three phenolics ranged from 88.7 to 105.7%. Finally, this approach was successfully applied to pharmacokinetic analysis of the three phenolics after oral administration of standard decoction and dispensing granules of C. cassia twigs in rats. Although the values of AUC0-t of vanillic acid and protocatechuic acid in standard decoction group were larger than those of the dispensing granule group, no significant difference was observed for the two groups. Of note, the elimination rates of vanillic acid were slower in the standard decoction group than the dispensing granule group.

Study on spectrum-effect correlation for screening the effective components in Fangji Huangqi Tang basing on ultra-high performance liquid chromatography-mass spectrometry.

BACKGROUD: Fangji Huangqi Tang (FHT) is a traditional Chinese medicine formula. Our previous work found that FHT could improve glomerular filtration function. The research on the effective materials basis of FHT was rarely reported. PURPOSE: The effect indicators of glomerular filtration function were determined. The components in serum of FHT was detected and identified. The relationships between chemical spectra of serum and effect indicators were elucidated. STUDY DESIGN: The paper was to study the underlying correlations between the chemical spectra and the protective effect of FHT on glomerulus to reveal the potential effective compounds in FHT. METHODS: For the serum pharmacochemistry study, the biological samples were collected according to a time schedule designed carefully in advance. The fingerprint chromatograms of rat serum after oral administration of FHT were established by UHPLC-ESI-Q-TOF-MS technique. Meanwhile, in the pharmacodynamics research, the protective effects of FHT on glomerulonephritis were evaluated by detecting the contents of cystatin C (Cys C), blood urea nitrogen (BUN) and serum creatinine (Scr). Then, the spectrum-effect relationships between UHPLC fingerprints and anti-adriamycin nephrosis activities were evaluated using canonical correlation analysis (CCA) statistical method. RESULTS: As a result, 105 peaks were identified from rat serum samples, which turned out to be 26 original compounds of FHT as well as 79 metabolites. According to the CCA results, eleven components were finally found to be the main anti-adriamycin nephrosis components. CONCLUSIONS: The model successfully discovered the spectrum-effect relationships of FHT, which showed a representative way to discover the primary active ingredients from the complex herbal medicine system.

An herbal formula attenuates collagen-induced arthritis via inhibition of JAK2-STAT3 signaling and regulation of Th17 cells in mice.

Wenjinghuoluo prescription, a traditional Chinese medicine compound treatment of rheumatoid arthritis characterized by wind-cold-dampness arthralgia, contains five herbs, namely, C. cassia Presl., Cinnamomum cassia Presl., Paeonia lactiflora Pall., Saposhnikovia divaricate (Turcz.) Schischk., and Clematis chinensis Osbeck. We have reported that WJHL could inhibit the production of inflammatory mediators in immune cells. This study explored the effect and mechanism of WJHL on collagen-induced arthritis mice. WJHL could significantly improve clinical arthritic conditions; inhibit bone erosion and osteophyte formation in joints; decrease expression of proinflammatory cytokines (TNF-α, IL-1ß, IL-6, and IL-17); reduce protein expression levels of JAK2, p-JAK2, STAT3, p-STAT3 and gene expression levels of JAK2, STAT3, IL-17A, RORγt mRNA; elevate osteoprotegerin and Foxp3 mRNA levels and lower Th17 cell proportions in splenocytes. Results suggest that WJHL, specifically regulating the JAK2/STAT3 pathway and Th17 cells, may be a promising herbal medicine candidate for the treatment of RA.

Global and untargeted metabolomics evidence of the protective effect of different extracts of Dipsacus asper Wall. ex C.B. Clarke on estrogen deficiency after ovariectomia in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Dipsacus asper Wall. ex C.B. Clarke (DA) is an effectively traditional Chinese medicine for treating osteoporosis and bone fracture. Until now, studies on pharmacological mechanism of DA mostly centered on cell and gene level, little is known about its metabolic signatures. The aim of this study is to investigate the anti-osteoporosis effects of crude and wine-processed DA by global and untargeted metabolic profiling of rats serum, liver and kidney derived from sham, model and treated groups. METHOD: A total of 25 female Wistar rats were divided into five groups: sham group, model group, E2, crude and wine-processed DA treated group. The treatment rats were orally administered 17ß-estradiol, crude and wine-processed DA extract at a therapeutic dose once daily throughout the experimental period, while sham group and model group were orally gavaged approximately volume of saline solution. After 16 weeks, all serum, liver and kidney samples of five groups were collected and their metabolomic alterations were monitored by gas chromatography-mass spectrometry (GC-MS). The resulting dataset was analyzed by principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA). The identification of all potential biomarkers was performed using reference standard or NIST library. Moreover, clinical chemistry and biomechanical analysis were also performed to ensure the success of the osteoporosis model and to validate the anti-osteoporosis effect of crude and wine-processed DA. RESULTS: Clear separation trend among sham, model and treatment group was observed in PCA score plot. The anti-osteoporosis effect of DA and wine-processed DA can be indicated in PLS-DA score plots. A total of 80 and 74 metabolite biomarkers were identified for DA and wine-processed DA treated groups, respectively. Pathway analysis revealed that phenylalanine, tyrosine and tryptophan biosynthesis, valine, leucine and isoleucine biosynthesis, methane metabolism, glycine, serine and threonine metabolism, galactose metabolism were the major intervened pathways. Compared with model group, levels of all biomarkers were gradually restored to normal after administration of DA and wine-processed DA. CONCLUSION: The anti-osteoporosis effect of DA and wine-processed DA has been reliably confirmed by the metabolomics approach. The osteoporosis might be prevented by DA and wine-processed DA via intervening amino acid metabolism, carbohydrate metabolism and energy metabolism in vivo in rats.

Untargeted serum metabolomics reveals Fu-Zhu-Jiang-Tang tablet and its optimal combination improve an impaired glucose and lipid metabolism in type II diabetic rats.

Fu-Zhu-Jiang-Tang tablet, a six-herb preparation, was proved to show beneficial effects on type II diabetes patients in clinical. This study aims to optimize the component proportion of the six-herb preparation and explore the serum metabolic signatures of type II diabetes rats after treatment with Fu-Zhu-Jiang-Tang tablet and its optimal combination. The component proportion of the preparation was optimized using uniform experimental design and machine learning techniques. Untargeted GC-MS metabolomic experiments were carried out with serum samples from model group and treatment groups. Data were normalized, multivariate and univariate statistical analysis performed and metabolites of interest putatively identified. 23 metabolites were significantly changed by Fu-Zhu-Jiang-Tang tablet treatment and the majority of these were decreased, including various carbohydrates (glucose, mannose, fructose, allose and gluconic acid), unsaturated fatty acids (palmitic acid, 9-octadecenoic acid, oleic acid, arachidonic acid), alanine, valine, propanoic acid, 3-hydroxybutyrate, along with pyrimidine and cholesterol. Increased concentrations of oxalic acid, leucine, glycine, serine, threonine, proline, lysine and citrate were observed. In the optimal combination-fed group, 21 metabolites were significantly affected and strikingly, the magnitudes of changes here were generally much greater than that of Fu-Zhu-Jiang-Tang tablet treated rats. 18 metabolites affected in both groups included various carbohydrates (mannose, glucose, allose, fructose and gluconic acid), unsaturated fatty acids (palmitic acid, 9-octadecenoic acid, oleic acid and arachidonic acid), short-chain fatty acids (oxalic acid, 3-hydroxybutyrate), and amino acids (alanine, valine, leucine, glycine, proline and lysine), as well as pyrimidine. Metabolites exclusively affected in optimal combination treated rat included succinic acid, cysteine and phenylalanine, whilst four metabolites (propanoic acid, citrate, serine and threonine) were only altered in Fu-Zhu-Jiang-Tang tablet treated rat. Our investigation demonstrated Fu-Zhu-Jiang-Tang tablet and its optimal combination treatments were able to ameliorate impaired glucose and lipid metabolism, down- regulate the high level of glucose to a lower level and reverse abnormal levels of metabolites in serum of type II diabetes rats. However, the optimal combination treatment was able to maximize the magnitudes of changes in some metabolites. These findings may be helpful in clarifying the anti-diabetic mechanism of FZJT tablet and its optimal combination.

A Study on the Chemical Compositions of the Yinqiaosan (Lonicerae and Forsythiae Powder) at Different Time of Later-decoction by Gas Chromatography Mass Spectrometry.

BACKGROUND: Yinqiaosan (Lonicerae and Forsythiae Powder), as a famous prescription of Dr. Wu Jutong in Qing dynasty of China, has the effects of diaphoresis cooling, fire-purging, and detoxicaton. It is mainly used in the treatment of influenza, hand-foot-mouth disease, esophagitis, pneumonia, acute tonsillitis, mumps, and other viral infections. It is one of the widely used traditional Chinese medicine prescriptions with proven curative effects in clinical use. OBJECTIVE: To research the material basis of Yinqiaosan decoction when decocting mint, herba schizonepetae in different length of later-decoction time, to find the influence on volatile components of Yinqiaosan decoction decocted later in different length of time, to lay the foundation to further clarify the after-decoction mechanism of Yinqiaosan, and the specification of Yinqiaosan decoction process. MATERIALS AND METHODS: Gas chromatography mass spectrometry method is used to analyze the volatile components of Yinqiaosan decoction samples decocted for 0, 3, 5, 8, and 10 min. RESULTS: Later-decocting mint and herba schizonepetae at different time when decocting Yinqiaosan had a significant influence on the volatile components of the solution. 54 different chemical components were identified: 25 were identified when later-decocting the sample for 3 min; 13 were identified when later-decocting the sample for 5 min; 11 were identified when later-decocting the sample for 8 min; 7 were identified when later-decocting the sample for 10 min; and 26 were identified when later-decocting the sample for 0 min. There were more volatile components in the sample after-decocted for 3 min. A total of 54 different chemical components were identified in different later-decocting solution samples. These components form the basis of the Yinqiaosan drug effect. CONCLUSIONS: The length of later-decoction time of mint and herba schizonepetae was confirmed to be 3 min when decocting Yinqiaosan. SUMMARY: Later-decocting mint and herba schizonepetae at different time had a significant influence on the volatile components of the solutionFifty-four different chemical components were identified in different later-decocting solution samplesThere were more volatile components in the sample after-decocted for 3 minThe volatile components content was high. These components form the important basis of the Yinqiaosan drug effect.Total ion flow diagram of volatile oils in the Yinqiaosan sample with mint, herba schizonepetae after 3 min decoction. Abbreviations used: GC-MS: Gas chromatography mass spectrometry, TCM: Traditional Chinese medicine.

Positive skeletal effect of two ingredients of Psoralea corylifolia L. on estrogen deficiency-induced osteoporosis and the possible mechanisms of action.

Estrogen replacement therapy (ERT) is utilized as a major regime for treatment of postmenopausal osteoporosis at present. However, long-term supplement of estrogen may cause uterine hyperplasia and hypertension leading to a high risk of endometrial cancer and breast cancer. Psoralea corylifolia L. has long been used as tonic and food additives in many countries. Previous studies had found two ingredients in P. corylifolia L.: bavachin and bakuchiol exhibited osteoblastic activity. The present study was designed to investigate the protective effect of bakuchiol and bavachin on ovariectomy-induced bone loss and explore the possible mechanism. In vivo, bakuchiol and bavachin could prevented estrogen deficiency-induced bone loss in ovariectomized rats without uterotrophic activity. In vitro studies suggested that bakuchiol and bavachin induced primary human osteoblast differentiation by up-regulating the Wnt signalling pathway. This study suggests that such a bone-protective role makes them a promising and safe estrogen supplement for the ERT.

Transepithelial transport of phenolic acids in Flos Lonicerae Japonicae in intestinal Caco-2 cell monolayers.

The oral bioavailabilities of phenolic acids in Flos Lonicerae Japonicae beverage were low. The observation from an in vitro Caco-2 cell model showed that the absorptions of phenolic acids were mainly permeated via paracellular diffusion, and influenced by P-glycoprotein (P-gp), multidrug resistance-associated protein 2 (MRP2) and breast cancer resistance protein (BCRP). Besides, the Papp (AP→BL) values in Flos Lonicerae Japonicae were significantly higher than those of monomers, which was attributed to the decrease of efflux ratios (<1.0) influenced by flavones (luteoloside and luteolin) on the P-gp, but they were still poorly absorbed. The results indicated that the absorptions in Flos Lonicerae Japonicae as well as those of monomers were mainly restricted by the tight junctions (TJs). Food supplements (honey and propolis) or edible excipient (chitooligosaccharide) as TJ enhancers will be investigated to improve the functions of Flos Lonicerae Japonicae healthy beverages.

[Effects of Wine-processing on Rhei Radix et Rhizoma on Upper-energizer Disease and Effects on Activities of Energy Metabolism Enzymes in Liver].

OBJECTIVE: To compare the effects of crude and wine-processed Rhei Radix et Rhizoma on upper-energizer disease and hepatic energy metabolism in mice. METHODS: The streptococcal pneumonia rats model and acetic acid burning mouth ulcers rats model were established and randomly divided into three groups: model group, crude Rhei Radix et Rhizoma group and wine-processed Rhei Radix et Rhizoma group. The pathologic changes were observed after the rats had been administrated with water extracts of crude and wine-processed Rhei Radix et Rhizoma respectively. The normal ICR mice were randomly divided into three groups: control group, crude Rhei Radix et Rhizoma group and wine-processed Rhei Radix et Rhizoma group. The influence of water extracts of crude and wine-processed Rhei Radix et Rhizoma on the activities of Na+, K-ATPase, Ca2+ -ATPase and succinic dehydrogenase(SDH) in the mice were compared. RESULTS: Compared with the crude one,the wine-processed Rhei Radix et Rhizoma significantly decreased the inflammation scores (P <0. 05), and promoted the tissue repair of acetic acid burning mouth ulcers rats model. The wine-processed one could also obviously reduce and normalize the level of leucocyte and neutrophilic granulocyte, lower the TNF-α level (P <0. 05), and relieve inflammatory exudation of the lung tissue. The inhibitory effects of wine-processed Rhei Radix et Rhizoma on the activities of SDH, Ca2+-ATPase and Na+, K + -ATPase were weaker than those of the crude one (P > 0. 05). CONCLUSION: After having been processed with wine, the efficacy of Rhei Radix et Rhizoma on upper-energizer disease is enhanced, and the inhibition on the activity of energy metabolism enzyme in liver tends to be weakened.

[Effect of emodin in attenuating endoplasmic reticulum stress of pancreatic acinar AR42J cells].

OBJECTIVE: To explore the effect of emodin on endoplasmic reticulum (ER) stress of pancreatic acinar AR42J cells. METHOD: Rat pancreatic acinar AR42J cells were cultured in 6-well plates, and divided into the normal control group, the model group (with the final concentration at 1 x 10(-7) mol · L(-1) for cerulean and lipopolysaccharide at 10 mg · L(-1)) and the emodin group (10, 20, 40 µmol · L(-1)). Cells in each group were cultured in three multiple pores for 24 h, and their supernate was removed after cell attachment. The normal control group was added with haploids, the model group was added with the modeling liquid for haploids, and the treatment groups were added with different concentrations of emodin at 15-20 min before the modeling liquid. The cells were continuously cultured for 3 h under 37 °C and 5% CO2. Their intracellular protease and lipase expressions were detected with kits. The cellular morphology was observed under optical microscope. The level of calcium in endoplasmic reticulum was measured under laser confocal microscopy. Western blot assay were used to determine the protein expression of ER-related signaling molecules. RESULT: Emodin could significantly inhibit levels of amylase, lipase and intracellular calcium and ER. CONCLUSION: Emodin could reduce pancreatic acinar cell injury induced by the combination of cerulean and lipopolysaccharide. Its action mechanism is correlated with the inhibition of intracellular calcium overload and ER stress.

Hierarchical targeted hepatocyte mitochondrial multifunctional chitosan nanoparticles for anticancer drug delivery.

The overwhelming majority of drugs exert their pharmacological effects after reaching their target sites of action, however, these target sites are mainly located in the cytosol or intracellular organelles. Consequently, delivering drugs to the specific organelle is the key to achieve maximum therapeutic effects and minimum side-effects. In the work reported here, we designed, synthesized, and evaluated a novel mitochondrial-targeted multifunctional nanoparticles (MNPs) based on chitosan derivatives according to the physiological environment of the tumor and the requirement of mitochondrial targeting drug delivery. The intelligent chitosan nanoparticles possess various functions such as stealth, hepatocyte targeting, multistage pH-response, lysosomal escape and mitochondrial targeting, which lead to targeted drug release after the progressively shedding of functional groups, thus realize the efficient intracellular delivery and mitochondrial localization, inhibit the growth of tumor, elevate the antitumor efficacy, and reduce the toxicity of anticancer drugs. It provides a safe and efficient nanocarrier platform for mitochondria targeting anticancer drug delivery.

Determination of liquiritigenin by ultra high performance liquid chromatography coupled with triple quadrupole mass spectrometry: Application to a linear pharmacokinetic study of liquiritigenin in rat plasma.

A simple, sensitive and rapid ultra high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method has been developed and validated for the quantification of liquiritigenin, a promising anti-tumor agent. Liquiritigenin and the internal standard were separated on an Agilent Extend C18 column and eluted with a gradient mobile phase system of acetonitrile and water. The analysis was performed on a negative ionization electrospray mass spectrometer via multiple reaction monitoring (MRM). Transitions of m/z 255.0→119.0 for liquiritigenin and m/z 269.0→117.0 for the IS were monitored. One-step protein precipitation with acetonitrile was used to remove impurities and extract the analytes from plasma. The method had a chromatographic run time of 4.5min and a good linearity in the range of 1-1000ng/mL. The precision (R.S.D.) of intra-day and inter-day ranged from 4.54 to 10.65% and 5.94 to 13.81%, respectively; while the accuracy of intra-day and inter-day ranged from 104.06 to 109.28% and 94.98 to 112.05%. The recovery and stability were also within the acceptable limits. The validated method was applied to a linear pharmacokinetic study of liquiritigenin in rat plasma for the first time.

Thermosensitive liposomes with higher phase transition temperature for targeted drug delivery to tumor.

Thermosensitive liposomes (TSL) in combination with local hyperthermia (HT) represent a promising tool for tumor specific drug delivery. The objective of the study was to investigate the influence of phase transition temperature (Tm) on the properties of TSL. High temperature triggered TSL (HTSL), low temperature triggered TSL (LTSL) and non-TSL (NTSL) were prepared and temperature sensitive release properties were extensively compared in different media. Mouse plasma was determined to have similar effect on the release profiles compared to human plasma, in which complete release were obtained at 38 °C and 40 °C for LTSL and HTSL, respectively. The temperature at which complete release achieved was found to be obviously lower than Tm. Brucine, an antitumor alkaloid, was encapsulated into different TSLs. After HT treatment, the viabilities of SMMC 7721 cells were determined to be 21.3±3.8% and 16.8±3.3% for 127 µM brucine LTSL and HTSL, respectively. Treating the tumor-bearing mice with LTSL, HTSL and NTSL led to significantly increased brucine uptake in the heated tumor site compared to the brucine solution group by 2.30, 3.80 and 2.26-fold, respectively. The results of this study suggested that Tm of TSL should be increased to obtain improved drug delivery efficiency to tumor.

Analysis of the influence of sulfur-fumigation on the volatile components of Angelicae sinensis Radix by comprehensive two-dimensional gas chromatography/time-of-flight mass spectrometry.

BACKGROUND: Sulfur-fumigation of Angelicae sinensis Radix causes changes in the structure and composition of volatile components. These changes alter the curative effect and the quality of A. sinensis Radix. MATERIALS AND METHODS: In this study, comprehensive two-dimensional gas chromatography coupled with time-of-flight mass spectrometry (GC × GC-TOFMS) was employed to investigate the influence of sulfur-fumigation on the volatile components, and to characterize and quantify the chemical composition of the volatile oil of A. sinensis Radix. RESULTS: The present study has shown that sulfur-fumigated A. sinensis Radix samples had significant loss of the main active compounds and a more destructive fingerprint profile compared to non-fumigated samples. CONCLUSION: From this study, it can be concluded that the combination of GC × GC and TOFMS has potential as a quality monitoring tool in herbal medicine and food processing industries.

Discrepancy between the effects of morronside on apoptosis in human embryonic lung fibroblast cells and lung cancer A549 cells.

Morroniside is a water-soluble compound extracted from the fruit of Cornus officinalis and is used to protect lung activity against aging. In the present study, the manner in which morroniside regulates normal lung and cancer cells was examined. The human embryonic lung fibroblast (HELF) cell line and lung cancer A549 cell line, and their responses to morroniside treatment, were examined. Results showed that morroniside reverses the apoptotic effect of H2O2 on HELF cell growth, protecting cell proliferation and normal cell morphology and inhibiting apoptosis. However, these effects were not present in A549 cells. Western blotting showed that morroniside also markedly downregulated retinoblastoma protein in HELF cells. These results suggest that morroniside treatment exhibits different effects on apoptosis in HELF and A549 cells, making it a viable compound for decreasing the side effects of anticancer medicines in normal cells.

Pharmacological evaluation of total alkaloids from nux vomica: effect of reducing strychnine contents.

The aim of the study was to investigate the possibility of improving the therapeutic efficacy of the total alkaloid fraction (TAF) extracted from processed nux vomica by reducing the strychnine contents. Most strychnine was removed from TAF to obtain the modified total alkaloid fraction (MTAF). The toxicity and pharmacokinetics of TAF and MTAF were further investigated and compared besides their antitumor, analgesic and anti-inflammatory activities. The results showed that the ratios of brucine to strychnine were 1:2.05 and 2.2:1 for TAF and MTAF, respectively, and the toxicity of TAF was about 3.17-fold higher than that of MTAF. Compared to brucine alone, the elimination of brucine was found to be inhibited by other alkaloids in TAF or MTAF except strychnine. Significantly increased pharmacological activities when administered by the oral route were obtained with MTAF in comparison to TAF and nux vomica powder (NVP). In summary, MTAF might replace NVP and TAF in the clinical application of Chinese medicine to obtain much higher efficacy.

A purge and trap technique to capture volatile compounds combined with comprehensive two-dimensional gas chromatography/time-of-flight mass spectrometry to investigate the effect of sulfur-fumigation on Radix Angelicae Dahuricae.

Sulfur-fumigation is known to reduce volatile compounds that are the main active components in herbs used in herbal medicine. We investigated changes in chemical composition between sun-dried and sulfur-fumigated Radix Angelicae Dahuricae using a purge and trap technique to capture volatile compounds, and two-dimensional gas chromatography/time-of-flight mass spectrometry for identification. Using sun-dried Radix Angelicae Dahuricae samples as a reference, the results showed that 73 volatile compounds, including 12 sulfide compounds, were found to be present only in sulfur-fumigated samples. Furthermore, 32 volatile compounds that were found in sun-dried Radix Angelicae Dahuricae samples disappeared after sulfur-fumigation. The proposed method can be applied to accurately discriminate sulfur-fumigated Radix Angelicae Dahuricae from different commercial sources.

Chemical differentiation of volatile compounds in crude and processed Atractylodis Macrocephalae Rhizoma by using comprehensive two-dimensional gas chromatography with time-of-flight mass spectrometry combined with multivariate data analysis.

In the present study, comprehensive 2D GC-TOF-MS combined with multivariate data analysis was applied to analyze the differences of the volatile components in crude and processed Atractylodis Macrocephalae Rhizoma (AMR) samples. As a result, 26 compounds that were found in crude AMR samples disappeared in processed AMR samples, and 19 compounds were newly generated and identified in AMR after processing with wheat bran. Meanwhile, principal component analysis demonstrated that there were significant chemical differences between crude and processed AMR samples, and processing procedure caused obvious quantitative and qualitative changes of volatile components in AMR. The established method could be used to explain the chemical differentiation between crude and processed AMR, and to further understand the processing mechanism of herbal medicines.

Drug-in-cyclodextrin-in-liposomes: a promising delivery system for hydrophobic drugs.

INTRODUCTION: Recently, the entrapment of hydrophobic drugs in the form of water-soluble drug-cyclodextrin (CD) complex in liposomes has been investigated as a new strategy to combine the relative advantages of CDs and liposomes into one system, namely drug-in-CD-in-liposome (DCL) systems. AREAS COVERED: For DCLs preparation, an overall understanding of the interaction between CDs and lipid components of liposomes is necessary and valuable. The present article reviews the preparation, characterization and application of DCLs, especially as antitumor or transdermal carriers. Double-loading technique, an interesting strategy to control release and increase drug-loading capacity, is also discussed. EXPERT OPINION: DCL approach can be useful in increasing drug solubility and vesicles stability, in controlling the in vivo fate of hydrophobic drugs and in avoiding burst release of drug from the vesicles. To obtain stable DCL, the CDs should have a higher affinity to drug molecules compared with liposomal membrane lipids. DCLs prepared by double-loading technique seem to be a suitable targeted drug delivery system because they have a fast onset action with prolonged drug release process and the significantly enhanced drug-loading capacity. In particular, DCLs are suitable for the delivery of hydrophobic drugs which also possess volatility.