Characterization and rapid identification of chemical constituents of NaoXinTong capsules by UHPLC-linear ion trap/Orbitrap mass spectrometry.

The BuChang NaoXinTong (BNC) capsule is a well-known, traditional, prescribed Chinese medication for the treatment of cardiovascular and cerebrovascular diseases. Nevertheless, the chemical profile of BNC has not been established. In the present study, ultra-high-pressure liquid chromatography coupled with linear ion trap-Orbitrap tandem mass spectrometry (UHPLC-LTQ-Orbitrap) has been developed for rapid and high-throughput screening of the preliminary chemical profile of BNC in both positive and negative ion modes. Twenty-five compounds were identified as the standard available compounds by comparing the retention time and high-resolution accurate mass. For the standard unavailable compounds, the structures were presumed based on high-accuracy protonated precursors and multi-stage mass spectrometry (MS(n)) using the proposed strategy. In particular, flavones, isoflavones, and tanshinones had the same skeleton. Therefore, the standards were utilized to characterize the fragment pathways and diagnostic fragment ions that could be applied for structural elucidation of their derivatives. Meanwhile, all the constituent groups of the compounds were detected in the individual herbs comprising BNC. Finally, a total of 178 components were identified or tentatively characterized in BNC, including 21 flavones and 6 flavone glycosides, 18 phenanthraquinones, and 22 terpenoids. The identification and structure elucidation of these chemicals provide essential data for further phytochemical studies, quality control, and pharmacological studies of BNC.

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.

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>

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>

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>

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>