Evaluation on Transdermal Absorption Properties and Efficacy of Huoxue Zhitong ;Cataplasm / 中国中医药信息杂志

Objective To study the effects of microemulsion/ethosomes on transdermal absorption properties and efficacy of Huoxue Zhitong Cataplasm. Methods The improved Franz diffusion cells were used for the in-vitro permeation experiment with rat skins as the barriers, which was used to evaluate the transdermal absorption properties. In the erxeriment, the contents of paeonol, eugenol and methyl salicylate were used as markers, and detected by ultra performance liquid chromatography to evaluate the transdermal absorption effects. The anti-inflammatory and analgesia activity were evaluated through the writhing plate experiments. Results The cumulative release rate of paeonol in Huoxue Zhitong Cataplasm, Microemulsion Huoxue Zhitong Cataplasm and Ethosomes Huoxue Zhitong Cataplasm were, in order, 65.30%, 61.30%and 60.20%in 24 h;eugenol were, in order, 51.08%, 54.71% and 55.66% in 24 h; methyl salicylate were, in order, 49.20%, 65.17% and 72.15% in 24 h. Furthermore, Microemulsion Huoxue Zhitong Cataplasm high-dose group and Ethosomes Huoxue Zhitong Cataplasm medium-dose group had good effects on reducing the inflammatory exudate of peritoneal capillary and capillary permeability (P<0.05) in animal models. Conclusion Huoxue Zhitong Cataplasm based on microemulsion/ethosomesnano-technology has good transdermal absorption properties and efficacy.

LC-MS quantification and pharmacokinetics of the multi-constituents of Huangqin Tang in rat plasma after different single oral doses / 药学学报

The current study aims to investigate the pharmacokinetic properties of Huangqin Tang on different oral doses. An LC-MS method for simultaneous determination of flavonoids and terpenoids in rat plasma was developed and validated. Plasma samples were treated with hydrochloric acid (containing 1% ascorbic acid), precipitated with acetonitrile, separated on a Zorbax SB-C18 column, detected by single quadruple mass spectrometry with an electrospray ionization interface, and quantified using selected ion monitoring mode. All pharmacokinetic parameters were processed by non-compartmental analysis using WinNonlin software. The results of specificity, linearity, intra-day and inter-day precisions, accuracy, and stability for LC-MS assay were suitable for the quantification of paeoniflorin, baicalin, wogonoside, baicalein, wogonin, oroxylin A, glycyrrhizic acid and glycyrrhetinic acid in rat plasma. The concentration-time profiles of baicalin, wogonoside, baicalein, wogonin, oroxylin A and glycyrrhizic acid showed double-peak phenomenon after Huangqin Tang was orally administered at 40 g x kg(-1) dose; all eight constituents in rat plasma showed good dose-exposure relationship within the dosage of 10-40 g x kg(-1); although plasma concentrations were different, the flavonoids with the same backbone showed the similar fate in the body with the corresponding dosage. In conclusion, the LC-MS assay was successfully applied for the pharmacokinetic study of multi-constituents of Huangqin Tang with different doses. Additionally, these constituents demonstrated good pharmacokinetic properties in the body.

Influence of jinlingzi powder with different compatibility on activity of cytochrome P1 A2 from rat liver microsomes / 中国中药杂志

To illustrate the compability rule of Jinlingizi powder, by investigating the effects of Jinlingzi Powder with different compatibility on the enzymatic activity of cytochrome P1 A2 (CYP1A2) from rat liver microsome. The different compability of Jinlingizi powder is designed, based on the orthogonal array L9 (3(4)). In vitro test, rat liver microsomes incubation system is applied to detect the 50% inhibitory concentraton of Jinlingzi powder with different compatibility to cytochrome P1A2 (CYP1A2) enzyme. In vivo experiments, rats is treated orally with the different compability of Jinlingizi powder for 5 days, then be injected with probe drug phenacetin. The biosample from liver tissue is obtained by microdialysis probe, then analysisd by HPLC. The concentration-time data are modulated by software WinNonlin. IC50 data show no significant inhibitory activty to cytochrome P1 A2. Acetaminophen and phenacetin PK parameters indicate that the different compability of Jinlingizi powder can modulate the CYP 1A2 mediated metabolism, which is associate with the compatibility of Jinlingzi powder.

Comparative study on pharmacokinetics of six major alkaloids in Zuojin Wan microemulsion based gel and hydrogel / 中国中药杂志

<p><b>OBJECTIVE</b>To compare the pharmcoknetic parameters of six major alkaloids in the two drug delivery system of Zuojin Wan, by LC-MS assaying the six major alkaloids plasma concentration.</p><p><b>METHOD</b>The blood samples were collected at different time after transdermal administration. The plasma concentration of six major alkaloids were detected by LC-MS, then the concentration-time data are modulated by software WinNonlin.</p><p><b>RESULT</b>Took the six alkaloids (berberine palmatine coptisine jateorhizine evodiamine rutecarpine) as index components, the relative bioavailability were 131%, 127%, 108%, 121%, 92%, 109%, respectively, the ratio of Ka were 10.5, 5.1, 3.7, 0.8, 1.8, 1.5, respectively.</p><p><b>CONCLUSION</b>The LC-MS can be applied in the determination of six major alkaloids plasma concentration. The pharmcoknetic parameters indicated that Zuojin Wan microemulsion gel delivery system can accelerate the transdermal absorption rate of Zuojin Wan, compared with the hydrogel drug delivery system.</p>

Antiatherogenic effect of Radix Salviae Miltiorrhizae and Fructus Crataegi on experimental atherosclerosis in rats / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the antiatherogenic effect and possible mechanisms of the extracts of Radix Salviae Miltiorrhizae (RSM) or Fructus Crataegi (FC), as well as their interaction.</p><p><b>METHOD</b>Wistar rats were randomly divided into 2 groups: normal group and model group. The atherosclerotic model rats were injected VD3 and ovalbumin, while fed with high cholesterol diet. After the model was determined successfully, all model rats were divided into normal group, model group, Xuezhikang group, RSM group, FC group, mixture of RSM and FC group. Each group was given the corresponding drugs for 4 weeks. After 12 weeks, blood serum were analyzed for total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C), superoxide dismutase ( SOD), malondialdehyde (MDA) and nitric oxide (NO). And the blood plasma also analyzed for levels of endothelin (ET), 6-keto prostaglandin F1alpha (6-keto-PGF1alpha), thromboxane B2 (TXB2), C-reactive protein (CRP), interleukin 6 (IL-6), interleukin 8 (IL-8), tumor necrosis factor alpha (TNF-alpha) and so on. At last, the pathological observation of aorta was carried out.</p><p><b>RESULT</b>Compared with those in model group, the TC, TG, LDL-C, ET, TXB2 and MDA levels and TXB2/PGF1alpha ratio were reduced, while the HDL-C, the serum SOD, No and 6-keto-PGF1alpha level were raised in the intervention groups. Although the levels of CRP, IL-6 and IL-8 were lower than model group, there was no obvious effect on the releasing of TNF-alpha.</p><p><b>CONCLUSION</b>RSM and FC could inhibit the atherogenesis formation and development, which might be due to regulating the lipid metabolism, enhancing the antioxidation, and reducing the release of inflammatory factors.</p>

Effects of Wuji pill compound with different compatibility on cytochrome P450 CYP3A1/3A2 in rat liver microsomes in vitro / 中国中药杂志

<p><b>OBJECTIVE</b>Wuji pill is a prescription of traditional Chinese medicine(TCM) and was composed of Rhizoma Coptidis, Fructus Evodiae Rutaecarpae and Radix Paeoniae Alba. The aim of this research is to investigate the effects of Wuji pill compound with different compatibility on the levels of enzymic activity of cytochrome P450 CYP3A1/3A2 in rat liver microsomes in vitro, and to confirm the compatibility mechanism of Wuji pill from the point of relationships between compound prescription of TCM and metabolism.</p><p><b>METHOD</b>With testosterone being a probe, the levels of enzymic activity of CYP3A1/3A2 were detected by HPLC, which were suppressed by Wuji pill with different compatibility in vitro.</p><p><b>RESULT</b>The IC50 of Rhizoma Coptidis, Fructus Evodiae Rutaecarpae, Radix Paeoniae Alba and 1"-9" of different level Wuji pill is: 38.96, 871.96, 15 519.17, 43.17, 60. 47, 276.12, 133.40, 118.08, 88. 47, 64. 36, 35. 13 and 39. 91 mg x L -', respectively. Rhizoma Coptidis and 1-9" of Wuji pill can suppress the enzymic activity of CYP3A1/3A2 significantly, and the capability of Rhizoma Coptidis in Wuji pill of action on CYP3A1/3A2 can be modified by different composition of Fructus Evodiae Rutaecarpae and Radix Paeoniae in Wuji pill, and there are statistical differences among the IC50 of 1#-9# of Wuji pill. While the ratio of Rhizoma Coptidis raises up in Wuji pill, Wuji pill may suppress the enzymic activity of CYP1A2 largely.</p><p><b>CONCLUSION</b>The reason why Wuji pill with different compatibility has different pharmacodynamics and pharmacokinetics characteristics is likely to lie in the difference of the capability of Wuji pill with different compatibility on CYP3A1/3A2. [Key words] Wuji pill; CYP3A1/3A2; testosterone; HPLC; different compatibility prescription of traditional Chinese medi-cine</p>

Experimental study on antitumor effects of extracts from Actinidia argutaor / 中国中药杂志

<p><b>OBJECTIVE</b>To observe the inhibitory effect of extract from Actinidia argutaor on in vivo and in vitro carcinomata, and explore its mechanism.</p><p><b>METHOD</b>The in vivo S180 and H22 model were used to observe the effect of A. argutaor on inhibitory rate of carcinomata, organ relative weight of spleen and thymus gland and the release of tumor necrosis factor. A549 cells were exposed to extract from A. argutaor with different concentrations for 24, 48, 72 hours. MTT assay was used to evaluate the inhibiting effects of extract from A. argutaor on the proliferation of the cells. Flow cytometry was applied to detect cell cycle.</p><p><b>RESULT</b>The inhibitory effects of the extracts on in vivo and in vitro carcinomata were observed, the inhibitory rate for S180 and H22 line was 33.32% and 34.62% respectively. The extracts could inhibit the proliferation of A549 cells during G0-G1 period and significantly decrease the cell ratio of S stage.</p><p><b>CONCLUSION</b>The extracts from A. argutaor showed a good antineoplastic activity.</p>

Methodology overview of perfused rat intestine-liver preparation / 中国中药杂志

Since pang set up the perfused rat intestine-liver preparation and applied it to study the disposition of enalapril, this model has been widely considered to have the particularly advantage in studying the absorption, metabolism and first-pass effect. Now the methods and applications are to be reviewed and the perspective is to be discussed.

Influence of gingko extract on metabolism of simvastatin / 中国中药杂志

<p><b>OBJECTIVE</b>To conclude the possible interaction between gingko extract and simvastatin, by studing the effect of gingko extract on vitro metabolism of simvastatin and involving critical metabolic enzyme, which can guide the clinicians to use them rationally (propose good guideline for rational using of the two medicine mentioned above).</p><p><b>METHOD</b>Thirty-two female SD rats were randomly separated into 4 groups, including negative control group. High dose of gingko extract. Low dose of gingko extract and positive control group. All groups were administered for 10 days with stomach tube, and then the quantity of liver microsome protein, the activity of CYP3A were determined by spectrophotograph simvastatin was incubated with the liver microsome, and the effect of gingko extract on its metabolism was estimated by measuring the amount of simvastatin by HPLC.</p><p><b>RESULT</b>Comparing with the negative contrast group: the quantity of liver microsome protein, the activity of CYP3A and the metabolism of simvastatin in positive control group were all increased markly (P < 0.05). In high dose group, the quantity of liver microsome protein and the activity of CYP3A were both increased significantly (P < 0.05), and the metabolism of simvastatin also accelerate obviously (P < 0.05). But in the low dose group significant distinction of every index was not found.</p><p><b>CONCLUSION</b>High dose of gingko extract can induce the activity of CYP3A, and promote the metabolism of simvastatin, so the medical interaction should be focused when gingko extract is coadministered with simvastatin and other substracts of CYP3A.</p>