Background: Curcumin (CUR), a natural isolated compound from turmeric, helps in fighting many diseases, but the broad application of curcumin has been limited ascribed to low bioavailability. Objective: The aim of this study is to pursue the enhancement of curcumin bioavailability through coadministration of vitamin C. Methods: Such purpose was achieved through the analysis of curcumin pharmacokinetics by highperformance liquid chromatography coupled with electrospray ionization - tandem mass spectrometry (HPLC - ESI - MS/MS). The plasma was separated on a C 18 reverse-phase column using acetonitrile and ammonium formate solution (pH 6.5; 2.0 mM) at 0.8 mL/min. MS/MS detection was carried out in negative mode using mass patterns of m/z 367.0 > 216.7 for curcumin and m/z 265.2 > 223.9 for internal standard (honokiol). Results: Successful application of the proposed method in the pharmacokinetic study presented clear changes in key pharmacokinetic parameters, including the growth of AUC (0-t) up to 2.4 times, a 2.2- fold increase of C max , 2.2-fold loss of CL, and 1.5-fold diminishment of t 1/2 . Conclusion: An HPLC-ESI-MS/MS method for the determination of curcumin in rat plasma and validated the improvement of bioavailability of curcumin through co-administration of vitamin C was determined. These changes were reasoned to the inhibition of lipid peroxidation induced by the use of vitamin C. Such a simple strategy is possible to become an alternative for enhancing curcumin efficiency in practice.

Bornyl caffeate was initially discovered as a bioactive compound in medicinal plants. Despite the promising pharmacological activities including anti-tumor and antibacterial activities, the pharmacokinetics of the compound remain open. This work developed a high performance liquid chromatography-tandem mass spectrometric method for the determination of bornyl caffeate and caffeic acid (major metabolite and a main unit of bornyl caffeate) in vivo. Successful application of the method included identification of its metabolites and investigation on the drug pharmacokinetics. A total of 30 compounds were identified as the metabolites of bornyl caffeate in rats. We attributed these metabolites to phase I metabolic routes of reduction, oxidation, hydrolysis and phase II metabolic reactions of glucuronidation, sulfation, O-methylation and glycine. Glucuronidation, sulfation, O-methylation and reduction were the main metabolic pathways of bornyl caffeate. The method presented a linear range of 1-4000 ng mL-1. The pharmacokinetic profile of bornyl caffeate was found to be a three compartment open model, while caffeic acid fitted to a two compartment open model when it was administered alone or served as the main metabolite of bornyl caffeate. The time to peak concentration (T max) and the maximum plasma concentration (C max) of bornyl caffeate were 0.53 h and 409.33 ng mL-1. Compared with original caffeic acid, the compound displayed an increased half-life of elimination (T 1/2β), area under the concentration time curve from 0 to t (AUC0-t ) and area under the concentration time curve from 0 to ∞ (AUC0-∞), a decreased half-life of absorption (T 1/2α) and an identical C max. Taking together, we concluded that bornyl caffeate is able to rapidly initiate therapeutic effect and last for a relatively long time in rats; metabolic pathways of O-methylation and reduction is key to interpret the mechanism and toxicity of bornyl caffeate.

AIMS:In clinical practice, herbal medicines have played an important role in the modulation of drug transporters through the combination of conventional prescription drugs, which necessitates the elucidation of herb-drug interactions. The present study was designed to investigate the inhibitory effects and mechanisms of benzaldehyde, vanillin, muscone, and borneol on P-glycoprotein (P-gp).METHODS:The effects of the 4 compounds on the intracellular accumulation of rhodamine-123 (Rho-123) in vinblastine-treated Caco-2 (VB-Caco-2) cells were studied by monitoring fluorescence intensity through a flow cytometry assay, and the effects of these compounds on Rho-123 transport through VB-Caco-2 monolayers and Rho-123 intestinal absorption in the rat everted gut sac were investigated by high-performance liquid chromatography. Moreover, P-gp expression in VB-Caco-2 cells was assessed using flow cytometry and Western blot analysis, and the relative ABCB1 mRNA level was determined by Real-time RT-PCR.KEY FINDINGS:The results showed that benzaldehyde, vanillin, muscone, and borneol significantly increased Rho-123 uptake in VB-Caco-2 cells, increased the absorption rate and apparent permeability coefficient of Rho-123 in rat jejunum and ileum, and decreased the efflux ratio of Rho-123 from 6.52 to less than 2 during transport across VB-Caco-2 cell monolayers. In addition, these compounds reduced the protein and ABCB1 mRNA levels of P-gp in VB-Caco-2 cells.CONCLUSIONS:These data indicate that benzaldehyde, vanillin, muscone and borneol could effectively reverse multidrug resistance via inhibiting the P-gp function and expression pathway. The data provide fodder for further investigation into the interaction between the 4 compounds and other drugs transported by P-gp.

OBJECTIVE To investigate effect of safflower-liquorice on vasomotion of mesenteric artery in rats with cold coagulation and blood stasis induced by cold stress.METHODS Cold coagulation and blood stasis model rats were induced by cold stress for 30 days.Adrenergic receptor-mediated vosoactivity and endothelium-dependent relaxation on rat mesenteric artery ring segments were monitored by a myograph system.RESULTS Compared with control arterial segments,the contractile response curves of phenylephrine (PE) and adrenaline (AD) with ICI 118551 as well as the relaxation response curve of salbutamol (SAL) in the arterial segments from model rats were all shifted to right.The decreased maximum contraction (Emx)induced by PE and AD with ICI 118551 as well as the decreased maximum relaxation (Rmax) of SAL was seen in the arterial segments from model rats.After oral administration of aqueous extracts of safflower and safflower-liquorice,the contractile response curves of PE and AD with ICI 118551 as well as the relaxation response curve of SAL in the mesenteric arterial segments were all shifted to left.The relaxation in endothelium-intact arterial segments induced by acetylcholine (Ach) was significantly decreased in model rats,and aqueous extracts of safflower and safflowerr-iquorice significantly attenuated the decreased relaxation in endothelium-intact arterial segments induced by Ach.The effect of aqueous extract of safflower-licorice on vasomotion of mesenteric artery in rats with cold coagulation and blood stasis was stronger than that of aqueous extract of safflower.CONCLUSION Safflower and safflower combined with liquorice exhibit better efficacy against cold coagulation and blood stasis syndrome by regulating alpha and beta adrenergic receptors and protecting endothelium of mesenteric artery in rats with cold coagulation and blood stasis.

Tanshinol borneol ester (DBZ) is a potential drug candidate composed of danshensu and borneol. It shows anti-ischemic and anti-atherosclerosis activity. However, little is known about its metabolism in vivo. This research aimed to elucidate the metabolic profile of DBZ through analyzing its metabolites using high-performance liquid chromatography combined with electrospray ionization quadrupole time-of-flight mass spectrometry. Chromatographic separation was performed on an Agilent TC-C18 column (150 × 4.6 mm, 5.0 μm) with gradient elution using methanol and water containing 0.2% (v/v) formic acid as the mobile phase. Metabolite identification involved analyzing the retention behaviors, changes in molecular weights and MS/MS fragment patterns of DBZ and its metabolites. As a result, 20 potential metabolites were detected and tentatively identified in rat plasma, urine and feces after administration of DBZ. DBZ could be metabolized to O-methylated DBZ, DBZ-O-glucuronide, O-methylated DBZ-O-glucuronide, hydroxylated DBZ and danshensu. Danshensu, a hydrolysis product of DBZ, could further be transformed into 12 metabolites. The proposed method was confirmed to be a reliable and sensitive alternative for characterizing metabolic pathways of DBZ and providing valuable information on its druggability.

Objective:To investigate whether the combination of Carthami Flos-Glycyrrhizae Radix et Rhizoma could improve energy metabolism in the tissue of rats with blood stasis syndrome,Carthami Flos-Glycyrrhizae Radix et Rhizoma on adenosine phosphate metabolism of tissues including heart,liver,spleen,lung and kidney were observed.Methods:The SD rats were randomly divided into 4 groups,namely blank control group,model group,Carthami Flos group and Carthami Flos-Glycyrrhizae Radix et Rhizoma group.The blood stasis model rats were made with cold stimulation in cold water ice bath.The blank control group and model group were given saline.The Carthami Flos group and Carthami Flos-Glycyrrhizae Radix et Rhizoma group were given aqueous extract of Carthami Flos and aqueous extract of Carthami Flos-Glycyrrhizae Radix et Rhizoma respectively by intragastric administration once per day according to experimental design for 15 days.At the end of the drug administration for 12 h,the blood and tissues (heart,liver,spleen,lung and kidney) were obtained and hemorheology parameters of rats were measured.The contents of adenosine triphosphate (ATP),adenosine diphosphate (ADP) and adenosine monophosphate (AMP) were determined by using high performance liquid chromatography (HPLC) method.Results:The whole blood viscosity and plasma viscosity were reduced in the dose group compared with the model group.The contents of adenosine phosphate in model rats after administration of the dose group were higher than those in model group,and the Carthami Flos-Glycyrrhizae Radix et Rhizoma group was better than that of the Carthami Flos group (P＜0.05).Conclusion:Carthami Flos and Carthami Flos-Glycyrrhizae Radix et Rhizoma herb-pair could improve the energy metabolism in rats with cold coagulation blood stasis,and the effect of Carthami Flos-Glvcvrrhizae Radix et Rhizoma was stronger than that of Carthami Flos.

Objective To explore the intestinal absorption-promoting effect of volatile oils of Shichangpu,benzoin and storax on Rhodamine-123 (Rho-123) and its mechanisms.Methods Rat in vitro everted gut sac (EGS) model was made.The EGS was filled with 1.0 mL K-R solution,and suspended in 45.0 mL 37 ℃ K-R solution with or without 60 μg/mL volatile oils of Shichangpu,benzoin or storax.After incubation for 30 min,Rho-123 was added in the experimental solution outside the EGS.Rho-123 content in the EGS was determined by high-performance liquid chromatography-fluorescence detector.The human colon carcinoma cell lines Caco-2 were cultured in DMEM and incubated with 80 μg/mL volatile oils of Shichangpu,benzoin or storax for 48 h.P-glycoprotein (P-gp) expression in Caco-2 cells was assessed using flow cytometry,and P-gp gene MDR1 mRNA expression was determined by qPCR.Results The volatile oils of Shichangpu,benzoin and storax each significantly increased the absorption rate constant and apparent permeability coefficient of Rho-123 in rat jejunum and ileum (P＜0.01),reduced P-gp expression and MDR1 mRNA level in Caco-2 cells (the decreased rates of P-gp expression were 53.15 ％,55.10％ and 61.86％,and of MDR1 mRNA levels were 55.41％,16.24％ and 38.46％,P＜0.01).Conclusion Inhibiting the protein and MDR1 mRNA expressions of P-gp may be one of the main mechanisms of volatile oils of Shichangpu,benzoin and storax in promoting Rho-123 intestinal absorption.