ABSTRACT
Objective: To evaluate the feasibility of the application of composite phospholipid liposome-based artificial skin membrane (CPLASM) for measuring biopharmaceutical properties of active fraction extracted from Xiangfu Siwu Decoction (XSD) via transdermal administration. Methods: The HPLC method was established for the determination of active ingredients (ferulic acid, tetrahydrocolumbamine, tetrahydropalmatine, senkyunolide I, and senkyunolide H) in active fraction of XSD. The oil/water partition coefficient values of these active ingredients were measured. The CPLASM was prepared to determine the in vitro permeability parameters of active fraction of XSD. The obtained parameters were further compared with those obtained by porcine ear skin. Results: The oil-water partition coefficients of ferulic acid, tetrahydrocolumbamine, tetrahydropalmatine, senkyunolide I, and senkyunolide H in active fraction of XSD (pH 5.5) were measured to be 1.220 ± 0.280, 0.670 ± 0.085, 0.920 ± 0.110, 1.040 ± 0.092, 1.030 ± 0.093 (n = 3), respectively. The permeability parameters of the active ingredients through porcine ear skin and CPLASM indicated a significant correlation (r > 0.9). Compared with the classical oil-water partition coefficients, the 6 h- cumulative permeation ratio of five active ingredients through CPLASM can be characterized as effectively predicting permeability parameters through porcine ear skin. Conclusion: The biopharmaceutical properties of active fractions from Chinese material medica can be effectively characterized by the application of CPLASM for the determination of in vitro permeability parameters of active ingredients.
ABSTRACT
To study the mechanism of Xiangfu Siwu decoction in treating primary dysmenorrhea, differentially-expressed proteins in ovary of primary dysmenorrheal mice with Xiangfu Siwu decoction administration were screened based on proteome technology using nano LC-LTQ-Orbitrap-MS/MS. Estradiol benzoate and oxytocin were used to produce dysmenorrheal mice model. The model mice were orally administrated with Xiangfu Siwu decoction for 3 days, and 1 h after the last administration, the ovary samples were collected. After protein denaturation, reduction, alkylation, desalination and enzymatic hydrolysis, identification was carried out by nano LC-LTQ-Orbitrap-MS/MS technology. The obtained data was processed by using Thermo Proteome discoverer 1.4 software. The differentially-expressed proteins were screened and identified, and their biological information was also analyzed. The significant differentially-expressed protein was checked using Western blot technology in ovary samples. A total of 106 differentially-expressed proteins were identified during the normal, model and administration group. Most of them participate cellular processes. Adherens junction and focal adhesion pathways play a regulatory role in various cell signaling pathways. Protein ADRM1 was validated. Compared to the normal group, it was up-regulated expression in the model group. After administration, the expression of ADRM1 was down-regulated. Through the comparative analysis, a series of differentially-expressed proteins involved in primary dysmenorrheal mice with Xiangfu Siwu decoction administration were obtained. Protein ADRM1 may become a target for Xiangfu Siwu decoction.
ABSTRACT
To study the effect of different penetration enhancers on the pharmacokinetic characters of six active components in Xiangfu Siwu transdermal patch (XBW) and optimize the best penetration enhancers. During the experiment, the patches containing different penetration enhancers were stuck on the rat's skin, and then the blood samples were acquired at different time points. Six active components in plasma were determined by UPLC-MS/MS. The main pharmacokinetic parameters were calculated with DAS software package. The total factor scores (F) of the plasma concentrations of six components at every time point in different groups were calculated using principle component analysis, and the areas under F versus time curves (AUCF-t) were employed to be the indexes for selecting penetration enhancers. The results demonstrated that compared with the control group, the AUCF-t from other groups increased prominently and furthermore, 5% menthol manifested the best effect. In this research, 5% menthol could remarkably promote the percutaneous penetration effect of the six active compounds in XBW, and it could provide a scientific basis for the preparation research of XBW.
ABSTRACT
Objective: To study the in vitro transdermal absorption properties of active fraction from Xiangfu Siwu Decoction (XSD). Methods: UPLC-MS/MS method was established for the determination of six main active ingredients (ferulic acid, paeoniflorin, albiflorin, tetrahydrocolumbamine, protopine, and tetrahydropalmatine) in active fraction of XSD (BW) and transdermal receiving liquid. The active ingredient group of six active ingredients was prepared according to their proportion in BW. The experiment of in vitro transdermal absorption was performed using vitro-abdominal skin of rats and improved Franz diffusion cell method. Results: UPLC-MS/MS method showed perfect specificity and the six ingredients performed well in linear relationship (r>0.997), precision (RSD≤2.66%), repeatability (RSD≤2.98%), stability (RSD≤3.99%), and average recovery rate [(95.22±5.48)%-(103.68±2.90)%]. The cumulative transmittance of the six ingredients displayed the same order between the active ingredient group and BW. The cumulative transmittance in descending order was as follows: ferulic acid>tetrahydrocolumbamine > tetrahydropalmatine>protopine>paeoniflorin≈albiflorin. Additional, transdermal absorption properties of the six ingredients in vitro were affected by the pH value of supply liquid significantly. Conclusion: The in vitro transdermal absorption behavior of the active ingredient group is consistent with BW and pH value can change the behavior of active ingredients in in vitro transdermal absorption.