Baochang Cai

Decocting-induced chemical transformations and global quality of Du–Shen–Tang, the decoction of ginseng evaluated by UPLC–Q-TOF-MS/MS based chemical profiling approach

An UPLC-Q-TOF-MS/MS based chemical profiling method was developed to evaluate decocting-induced chemical transformations in Du-Shen-Tang, the decoction of the root of Panax ginseng. Under the optimized UPLC and Q-TOF-MS/MS conditions, over 50 peaks were separated and detected in Du-Shen-Tang within 18 min. The components were identified by comparing the mass spectra and retention time with that of reference compounds, and/or tentatively assigned by elucidating low energy CID fragment ions as well as matching empirical molecular formula with that of the published known compounds. Totally 45 major ginsenosides were identified in Du-Shen-Tang, 21 of which were determined to be newly generated during the decoction of ginseng. The mechanisms involved were further deduced to be hydrolysis, dehydration, decarboxylation and addition reactions of the original ginsenosides in white ginseng through analyzing mimic decoctions of 13 pure reference ginsenosides. Significant difference in chemical profiles between decoctions of two batches of white ginseng suggested that storage duration or other factors significantly influenced the quality consistency of not only the crude drug but also the decoction (Du-Shen-Tang) of white ginseng.

Simultaneous determination of six active components in crude and processed Fructus Corni by high performance liquid chromatography

A simple and rapid HPLC method was established for simultaneously determining six active components in Fructus Corni. The six components were separated on an Agilent Zorbax Extend C18 column (250 mmx4.6 mm, 5 microm) and detected by diode array detector (DAD). Mobile phase was composed of (A) aqueous phosphoric acid (0.1%, v/v) and (B) acetonitrile phosphoric acid (0.1%, v/v) using a gradient elution. Analyses were performed at 30 degrees C with a flow rate of 1.0 mL/min and UV detection at 218 nm, 240 nm and 284 nm. All calibration curves showed good linear regression (r2>or=0.9999) within tested ranges. The LOD and LOQ were 0.11-1.69 microg/mL and 1.48-16.60 microg/mL, respectively. Overall intra-day and inter-day variations were less than 4.72%, and the average recoveries were 97.97-102.51% for the analytes. The developed method can be applied to the intrinsic quality control of Fructus Corni.

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.

Analgesic and anti-inflammatory activity and pharmacokinetics of alkaloids from seeds of Strychnos nux-vomica after transdermal administration: effect of changes in alkaloid composition.

ETHNOPHARMACOLOGICAL RELEVANCE Strychnos nux-vomica L. (Loganiaceae) is grown extensively in southern Asian countries. The dried seed of this plant, nux vomica, has been clinically used in Chinese folk medicine for improving blood circulation, relieving rheumatic pain, reducing swelling and treating cancer. AIM OF THE STUDY This study was carried out to investigate the effect of removing most strychnine from the total alkaloid fraction (TAF) extracted from nux vomica on analgesic and anti-inflammatory activity and pharmacokinetics after transdermal administration. MATERIALS AND METHODS Most strychnine was removed from TAF and the resulted modified total alkaloid fraction (MTAF) was obtained. The contents of strychnine and brucine in TAF and MTAF were determined. Then the analgesic and anti-inflammatory activity of TAF, MTAF, brucine and strychnine dissolved in hydrogel was compared after transdermal administration. Furthermore, in vitro and in vivo transdermal absorption profiles of brucine after administration of TAF, MTAF and brucine dissolved in hydrogel were also compared. RESULTS In contrast to TAF, most strychnine was removed from MTAF and the ratio of brucine to strychnine was adjusted from 1:1.8 to 2.7:1. MTAF showed significant analgesic activity in all the chemical-, thermal- and physical- induced nociception models, which indicated the presence of both centrally and peripherally mediated activities. MTAF also showed significant anti-inflammatory activity against xylene-induced ear edema. But TAF and strychnine demonstrated little activity in all those pharmacological tests. Brucine showed to be effective in acetic acid-induced writhing and xylene-induced ear edema test. Brucine in MTAF was absorbed more completely than it alone at the same dosage of brucine after transdermal administration. CONCLUSIONS The results from the present study appeared to support the viewpoint that most strychnine should be removed from TAF to improve analgesic and anti-inflammatory activity. The relatively higher pharmacological activity of MTAF compared to brucine alone is partly due to the enhanced transdermal absorption of brucine.

Supercritical fluid CO2 extraction and simultaneous determination of eight annonaceous acetogenins in Annona genus plant seeds by HPLC–DAD method

Annonaceous acetogenins (ACGs) isolated from Annonaceae plants exhibited a broad range of biological bioactivities such as cytotoxic, antitumoral, antiparasitic, pesticidal and immunosuppresive activities. However, their structures were liable to change at more than 60 degrees C and their extraction yields were low using traditional organic solvent extraction. In the present study, all samples from Annona genus plant seeds were extracted by supercritical carbon dioxide under optimized conditions and a high-performance liquid chromatography (HPLC) method was established for simultaneously determining eight ACGs. All of the eight compounds were simultaneously separated on reversed-phase C(18) column (250 mm x 4.6 mm, 5 microm) with the column temperature at 30 degrees C. The mobile phase was composed of (A) methanol and (B) distilled water, the flow rate was 1.0 ml/min and the detection wavelength was set at 220 nm. All calibration curves showed good linear regression (gamma>0.9995) within the test range. The established method showed good precision and accuracy with overall intra-day and inter-day variations of 0.87-2.53% and 1.91-3.42%, respectively, and overall recoveries of 95.81-105.39% for the eight compounds analyzed. The established method can be applied to evaluate the intrinsic quality of Annonaceae plant seeds. The determination results recover the content-variation regularities of various ACGs in different species, which are helpful to choose the good-quality Annonaceae plant seeds for anticancer lead compound discovery.

The effects of Rhizoma Zingiberis on pharmacokinetics of six Aconitum alkaloids in herb couple of Radix Aconiti Lateralis-Rhizoma Zingiberis.

ETHNOPHARMACOLOGICAL RELEVANCE Radix Aconiti Lateralis (Fuzi in Chinese, derived from the lateral roots of Aconitum Carmichaeli Debx.) is widely used for the treatment of heart failure, internal cold, arthralgia, diarrhea and edema for thousands of years. It was usually prescribed in combination with Rhizoma Zingiberis (Ganjiang in Chinese, derived from the dry rhizome of Zingiber officinale Rosc.) to decrease toxicity and increase efficacy. AIM OF THE STUDY In order to investigate the influence of Rhizoma Zingiberis on pharmacokinetics of six Aconitum alkaloids, i.e. aconitine (AC), hypaconitine (HA), mesaconitine (MA), benzoylaconine (BAC), benzoylhypaconine (BHA) and benzoylmesaconine (BMA), in Fuzi-Ganjiang herb couple, the comparative pharmacokinetics of six Aconitum alkaloids after oral administration of Fuzi and Fuzi-Ganjiang aqueous extract was carried out. MATERIALS AND METHODS A sensitive, specific and rapid LC-MS/MS method was developed to determine the six analytes in plasma. Then the rats were randomly divided into two groups and orally administered with Fuzi and Fuzi-Ganjiang aqueous extract. At designated time points after oral administration, the concentrations of the six Aconitum alkaloids in rat plasma were determined, and main pharmacokinetic parameters were investigated using 3P97 (Practical Pharmacokinetics Program Version 1.0). RESULTS Comparing with Fuzi group, both T1/2 and AUC0-t of AC and HA decreased (P<0.05), while T1/2, AUC0-t and Cmax of BAC, BHA increased (P<0.05) in Fuzi-Ganjiang group, which indicated that Ganjiang could promote the elimination of AC and HA and enhance the absorption of BAC, BHA and BMA. CONCLUSION The differences of pharmacokinetics of Aconitum alkaloids in rat plasma could support those of pharmacologics and toxicity in previous reports between Fuzi and Fuzi-Ganjiang herb couple. The results might be helpful in explaining the mechanism of combination of Fuzi-Ganjiang to decrease toxicity and increase efficacy.

Influence of lipid composition on the phase transition temperature of liposomes composed of both DPPC and HSPC

Objective: Phase transition of the lipid membrane is one of the most important properties of liposomes. The objective of this study was to investigate the influence of molar ratio of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and hydrogenated soy phosphatidylcholine (HSPC) on the phase transition temperature (Tm) of the liposomes. Materials and methods: The Tms of the liposomes with different phosphatidylcholine (PC) composition were determined by calcein release test and differential scanning calorimetry (DSC). Results: Only one phase transition was observed for liposomes composed of both DPPC and HSPC, indicating that DPPC and HSPC might combine into one phase with single phase transition. The Tm of the liposomes composed of both DPPC and HSPC was directly dependent on the molar ratio of the two PCs. Moreover, DPPC percentage and Tm relationship could be fitted with a linear equation (r2 > 0.98). In addition, the serum stability of the liposomes at 37°C was directly increased with the increase of DPPC percentage. When 10% DSPE-PEG2000 was added, the significant increase of calcein release at Tm and decrease at 37°C were observed. Discussion: It is easy to obtain liposomes with a Tm in between that of DPPC and HSPC by modifying the molar ratio of DPPC and HSPC. Conclusion: With the modification of Tm, the liposomes containing various ratios of DPPC and HSPC may have promising application potential in the field of thermosensitive liposomes (TSLs). After 10% DSPE-PEG2000 is added, a formulation of sterically stabilized liposomes with the proper thermal sensitivity can be obtained.

Investigation on the morphological protective effect of 5-hydroxymethylfurfural extracted from wine-processed Fructus corni on human L02 hepatocytes

AIM To determine the mode of action of 5-hydroxymethylfurfural (5-HMF) extracted from wine-processed Fructus corni on hepatoprotective activities, the effects of 5-HMF on H(2)O(2)-induced human L02 hepatocytes injury was examined. MTHODS: Hepatocytes L02 injured by H(2)O(2) was treated by 5-HMF. The morphological changes of the cells were observed under inverted phase-contrast, fluorescence, and transmission electron microscopy and the activities of caspase-9 and caspase-3 were tested by enzyme-linked immunosorbent detector. RESULTS It revealed that 5-HMF improved the morphology of H(2)O(2)-treated human L02 hepatocytes, and also inhibited the level of caspase-9 and caspase-3 of them. CONCLUSIONS These results suggested a morphological hepatocyte protective effect and the anti-apoptosis mechanism by 5-HMF.

Comparative pharmacokinetic and bioavailability studies of three salvianolic acids after the administration of Salviae miltiorrhizae alone or with synthetical borneol in rats.

Salviae miltiorrhizae is one of the most commonly used herbal plants in the treatment of numerous ailments including cardiovascular diseases for hundreds of years. According to the theory of traditional Chinese herbal medicine, S. miltiorrhizae is always used in combination with borneol to obtain better pharmacological effects. The purpose of this study was to investigate the effects of borneol on the pharmacokinetic and bioavailability of S. miltiorrhizae. The pharmacokinetics studying on rosmarinic acid, salvianolic acid A and salvianolic acid B which are the main active compounds of S. miltiorrhizae in rat plasma, was achieved using a optimal high-performance liquid chromatographic technique coupled with liquid-liquid extraction method. After administration of either single salvianolic acids or salvianolic acids in combination with borneol, plasma concentrations of rosmarinic acid, salvianolic acid A and salvianolic acid B of male Sprague-Dawley rats were determined at different time points (5, 10, 20, 30, 45, 60, 90, 120, 180, 240, 300, and 360 min). In comparison with salvianolic acid extract alone, there were statistically significant differences in pharmacokinetic parameters of rosmarinic acid, salvianolic acid B and salvianolic acid A, and the bioavailability of the three salvianolic acids increased by different degrees when the salvianolic acid extract and borneol were administered together. These results indicated that borneol could enhance the intestinal absorption, decrease the distribution and inhibit the metabolism of salvianolic acids.

Structure–activity relationships of diverse annonaceous acetogenins against human tumor cells

Twelve annonaceous acetogenins (ACGs) with different stereochemical structures and configuration were selected to test for their inhibitions on the growth of Hela, SMMC-7541, SGC-7901, MCF-7 and A-5408 tumor cell lines using MTT method. This was the first to simultaneously investigate effects of structural factors of stereochemical structures and configuration on cytotoxicities with structure-activity relationship. The present study showed that cytotoxic selectivities of ACGs with threo/trans/threo/trans/erythro stereochemical arrangement were gently more active than those with threo/trans/threo/trans/threo stereochemical arrangement, and ACGs with cis THF ring partly produced notable cytotoxic selectivities. Furthermore, ACGs with S configuration at C-24 exhibited gently more cytotoxic selectivities potency than those with R configuration at C-24.