[Effect of granules made by new-medicinal parts of Crocus sativus on hyperuricemia in rats and its mechanism].

To explore the effect of the granules made by new-medicinal parts of Crocus sativus(NMPCS) on hyperuricemia(HUA) in rats, the rat model of HUA was established by intramuscular injection of 3% potassium oxonate and intraperitoneal injection of 4% pyrazinamide. The content of serum uric acid was monitored every week for 3 consecutive weeks. After the experiment, the levels of serum uric acid, urine uric acid, serum creatinine, blood urea nitrogen(BUN), and xanthine oxidase(XOD) were determined. The protein and gene expressions of XOD were determined by Western blot method and fluorescence quantitative polymerase chain reaction(qPCR), and the morphological changes in the liver tissue were performed by hematoxylin-eosin(HE) staining. The results showed that as compared with the model group, the levels of serum uric acid in the positive drug group and the low, medium, and high-dose NMPCS groups were lower(P<0.05), the levels of urine uric acid in the high-dose NMPCS group were decreased(P<0.01), and there was no statistical difference in the medium and low-dose NMPCS groups. The levels of BUN in the high and low-dose NMPCS groups were decreased(P<0.05), and the levels of serum creatinine did not change in the administration groups. The positive drug group and the low, medium, and high-dose NMPCS groups significantly reduced the liver damage, with only a few hepatocytes vacuolization and a small number of red blood cells in the central venous area. The nephridial tissue structure was slightly abnormal, with a small number of red blood cell infiltration, and no obvious inflammatory cell infiltration was found in the glomerulus in these groups. No degeneration was found in renal tubular epithelial cells, with mild glomerular and tubular lesions and a small amount of sodium urate deposition and crystallization in the positive drug group and the low, medium, and high-dose NMPCS groups. The relative protein expressions of XOD in the positive drug group and the high dose NMPCS group were decreased(P<0.05), and the relative mRNA expressions of XOD in the positive drug group and the high and low-dose NMPCS groups were decreased as well(P<0.05). The above results show that NMPCS reduces uric acid in rats with HUA by regulating XOD, which provides a certain experimental basis for the development of NMPCS as a new medicine for the treatment of HUA.

[Analysis on transcriptionomic characteristics of Naoxintong Capsules in prevention of post-ischemic inflammation based on RNA-Seq technology].

In this research, high-throughput sequencing was used to investigate the mechanism of Naoxintong Capsules(NXTC) in prevention of post-ischemic inflammation. First, microglia BV-2 inflammatory model was induced by 1.0 µg·mL~(-1) LPS to investigate the effect of intestinal absorption solution of NXTC(NXTCIA) at different concentrations(62.5, 31.25, 15.63, 7.81 µg·mL~(-1)) on LPS-induced BV-2 inflammatory factors in microglia. Then, an RNA-Seq high-throughput sequencing method was performed to identify the differentially expressed mRNAs in microglia BV-2 after pre-treatment with NXTC. GO and KEGG enrichment analysis was used to screen the potential biological processes and related signaling pathways of NXTC in inhibiting inflammation. The results showed that four NXTCIA concentrations could significantly inhibit the release of LPS-induced inflammatory mediators in BV-2 in a dose-dependent manner. Furthermore, high-throughput sequencing results showed that 392 mRNA transcripts were reversed following pre-treatment with NXTC. GO enrichment analysis showed that the transcripts reversed by NXTC were mainly involved in Toll-like receptor signaling pathway, chemokine signaling pathway, and TNF signaling pathway. Taken together, our findings showed that NXTC treatment could provide protective effects against inflammatory response and the mechanism might be related to the regulation of Toll-like receptor signaling pathway, chemokine signaling pathway, and TNF signaling pathway.

Main active constituent identification in Guanxinjing capsule, a traditional Chinese medicine, for the treatment of coronary heart disease complicated with depression.

Guanxinjing capsules (GXJCs) are used in traditional Chinese medicine as a common therapy for coronary heart disease (CHD) complicated with depression. In this study, we aimed to identify the main active constituents in GXJCs and to investigate the mechanisms of GXJC action on CHD complicated with depression. The chemical constituent profile of the GXJC was identified by UHPLC-LTQ-Orbitrap assay, and oral bioavailability was evaluated to screen the GXJC drug-like chemical constituents. A total of 16 GXJC drug-like chemical constituents were identified. Then, putative targets of the GXJC drug-like chemical constituents were predicted using MedChem Studio, with 870 genes found to be the putative targets of these molecules. After that, a GXJC putative target-known CHD/depression therapeutic target network was constructed, and four topological features, including degree, betweenness, closeness and K-coreness, were calculated. According to the topological feature values of the GXJC putative targets, 14 main active constituents were identified because their corresponding putative targets had topological importance in the GXJC putative target-known CHD/depression therapeutic target network, which were defined as the candidate targets of GXJC against CHD complicated with depression. Functionally, these candidate targets were significantly involved in several CHD/depression-related pathways, including repairing pathological vascular changes, reducing platelet aggregation and inflammation, and affecting patient depression. This study identified a list of main active constituents of GXJC acting on CHD complicated with depression using an integrative pharmacology-based approach that combined active chemical constituent identification, drug target prediction and network analysis. This method may offer an efficient way to understand the pharmacological mechanisms of traditional Chinese medicine prescriptions.

[Protective effect and mechanism of scutellarin ethyl ester on focal cerebral ischemia induced by ligation of middle cerebral artery in rats].

To observe the protective effect of scutellarin ethyl ester on focal cerebral ischemia injury induced by middle cerebral artery occlusion in rats(MCAOR), and explore its mechanism. Totally 84 male SD rats were randomly divided into seven groups： sham-operated group, model group,positive drug group(niomdipine,12 mg•kg⁻¹), Brevisapin tablets group(48 mg•kg⁻¹), and high, middle and low-dose scutellarin ethyl ester groups(100, 50, 25 mg•kg⁻¹). The MCAOR model was prepared by using thread embolism method to observe the neurological function of rats, the area of cerebral infarction was measured with TTC, and the levels of MDA, SOD and NO in serum were detected with semiautomatic biochemistry analyzer.Ox-LDL and TNF-α cell injury models was established by treating HUVECs with 200 mg•L⁻¹ ox-LDL and 100 µg•L⁻¹ TNF-α,and the levels of MDA, SOD, NO, ET, 6-keto-PGF1α,TXB2, IL-1, IL-6, IL-8, ICAM-1 and PECAM-1 in the cell supernatant were determined. The results showed that scutellarin ethyl ester could effectively improve the neurological function of MCAOR rats, and significantly reduce the area of cerebral infarction. Compared with the model group, activities of SOD and NO in serum increased, while content of MDA decreased. In the cell supernatant, activities of SOD, 6-keto-PGF1α and NO increased, content of IL-1, IL-6, IL-8, ICAM-1, PECAM-1, TXB2, ET and MDA decreased, which indicated that scutellarin ethyl ester has a certain protective effect on focal cerebral ischemia injury induced by middle cerebral artery occlusion in rats, and its mechanism may be related to antioxidative stress, improvement of endothelial function and reduction in inflammatory reaction.

[Simultaneous determination of seven bioactive compounds and pharmacokinetics in rat plasma after oral administration of Yindan Xinnaotong Ruanjiaonang by UPLC-MS/MS].

To estabish ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for simultaneous determination of quercetin(QCT), isorhamnetin(ISR), kaempferol(KMF), ginkgolide A(GA), ginkgolide B(GB), ginkgolide C(GC) and bilobalide(BB) in rat plasma and investigate the pharmacokinetic process of seven compounds after oral administration of Yindan Xinnaotong Ruanjiaonang, The results indicated that all calibrations curves showed good linearity (r≥0.997 1). RSD of intra-day and inter-day precisions were all within 11%. The matrix effects and extraction recovery were in the range of 93.28%-103.6% and 72.43%-95.77% respectively. The peak concentration (Cmax) of QCT, ISR, KMF, GA, GB, GC and BB were (45.02±11.28), (49.90±13.82), (27.85±8.38), (76.31±18.19), (76.54±15.43), (35.35±10.28), (48.70±12.34) µg•L⁻¹, respectively. The peak time (tmax) of seven constituents were (0.33±0.11), (0.50±0.23), (0.33±0.14), (0.75±0.29), (1.0±0.35), (1.5±0.23), (0.75±0.50) h, respectively. UPLC-MS/MS method established in this research was proved to be so rapid and sensitive that it can be applied to the pharmacokinetic study of seven bioactive constituents in Yindan Xinnaotong Ruanjiaonang.

[Explore anti-atherosclerotic mechanism of component compatibility of Danshen and Shanzha based on network pharmacology and cell level].

To explore the anti-atherosclerotic mechanism of active component compatibility of Danshen and Shanzha (SC121) based on network pharmacology and in vitro research validation with cell model. On one hand, according to the chemical structures and pharmacological activities of the compounds reported in Danshen and Shanzha, 5 compounds, i.e., salvianolic acid B, tanshinone ⅡA, tanshinol, epicatechin and procyanidin B2 were chosen and used for network pharmacology analysis. Then the TCMSP（http://lsp.nwsuaf.edu.cn/tcmsp.php）was used for finding the network targets for 5 compounds from SC121. The signaling pathway associated with cardiovascular disease was analyzed by KEGG mapping, the biological process associated with cardiovascular disease was analyzed by Uniprot. And, the mechanism of SC121 was predicted by network pharmacology. In vitro cell model was subsequently performed for validation. HUVEC and RAW264.7 cell injuries and foam cell formation were constructed by ox-LDL, and the intervention effects of SC121 were assayed. The result showed that SC121 not only alleviated the damage of HUVEC and RAW264.7, lowered the ROS level, but also decreased the area of foam cell in a dose-dependent manner, which indicated that SC121 could inhibit the damage of endothelial cells and lower the oxidative stress. The experimental data validated the prediction of network pharmacology, and elucidated the mechanism of SC121's effect on AS.

[Rapid identification of chemical composition in safflower with UHPLC-LTQ-Orbitrap].

The UHPLC-LTQ-Orbitrap high resolution mass spectrometer was used to explore the chemical compositions in safflower. The rapid separation of the compositions was conducted by the UHPLC, following by high resolution full scan and MS2 scan, under the positive and negative ion mode. The chemical formula of compositions were deduced by full scan data in less than 5, then the potential structures were confirmed by the MS2 data. Forty-nine compounds were detected, of which 26 was identified, and 5 compounds was validated by the standard substances.

Yindanxinnaotong, a Chinese compound medicine, synergistically attenuates atherosclerosis progress.

Yindanxinnaotong (YD), a traditional Chinese medicine, has been introduced to clinical medicine for more than a decade, while its pharmacological properties are still not to be well addressed. This report aimed to explore the anti-atherosclerosis properties and underlying mechanisms of YD. We initially performed a computational prediction based on a network pharmacology simulation, which clued YD exerted synergistically anti-atherosclerosis properties by vascular endothelium protection, lipid-lowering, anti-inflammation, and anti-oxidation. These outcomes were then validated in atherosclerosis rats. The experiments provided evidences indicating YD's contribution in this study included, (1) significantly reduced the severity of atherosclerosis, inhibited reconstruction of the artery wall and regulated the lipid profile; (2) enhanced antioxidant power, strengthened the activity of antioxidant enzymes, and decreased malondialdhyde levels; (3) significantly increased the viability of umbilical vein endothelial cells exposed to oxidative stress due to pretreatment with YD; (4) significantly reduced the level of pro-inflammatory cytokines; (5) significantly down-regulated NF-kB/p65 and up-regulated IkB in the YD-treated groups. Overall, these results demonstrated that YD intervention relieves atherosclerosis through regulating lipids, reducing lipid particle deposition in the endothelial layer of artery, enhancing antioxidant power, and repressing inflammation activity by inhibiting the nuclear factor-kappa B signal pathway.

Deciphering the pharmacological mechanism of the Chinese formula huanglian-jie-du decoction in the treatment of ischemic stroke using a systems biology-based strategy.

AIM: Huanglian-jie-du decoction (HLJDD) is an important multiherb remedy in TCM, which is recently demonstrated to be effective to treat ischemic stroke. Here, we aimed to investigate the pharmacological mechanisms of HLJDD in the treatment of ischemic stroke using systems biology approaches. METHODS: Putative targets of HLJDD were predicted using MetaDrug. An interaction network of putative HLJDD targets and known therapeutic targets for the treatment of ischemic stroke was then constructed, and candidate HLJDD targets were identified by calculating topological features, including 'Degree', 'Node-betweenness', 'Closeness', and 'K-coreness'. The binding efficiencies of the candidate HLJDD targets with the corresponding compositive compounds were further validated by a molecular docking simulation. RESULTS: A total of 809 putative targets were obtained for 168 compositive compounds in HLJDD. Additionally, 39 putative targets were common to all four herbs of HLJDD. Next, 49 major nodes were identified as candidate HLJDD targets due to their network topological importance. The enrichment analysis based on the Gene Ontology (GO) annotation system and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway demonstrated that candidate HLJDD targets were more frequently involved in G-protein-coupled receptor signaling pathways, neuroactive ligand-receptor interactions and gap junctions, which all played important roles in the progression of ischemic stroke. Finally, the molecular docking simulation showed that 170 pairs of chemical components and candidate HLJDD targets had strong binding efficiencies. CONCLUSION: This study has developed for the first time a comprehensive systems approach integrating drug target prediction, network analysis and molecular docking simulation to reveal the relationships between the herbs contained in HLJDD and their putative targets and ischemic stroke-related pathways.

Fructus phyllanthi tannin fraction induces apoptosis and inhibits migration and invasion of human lung squamous carcinoma cells in vitro via MAPK/MMP pathways.

AIM: Fructus phyllanthi tannin fraction (PTF) from the traditional Tibetan medicine Fructus phyllanthi has been found to inhibit lung and liver carcinoma in mice. In this study we investigated the anticancer mechanisms of PTF in human lung squamous carcinoma cells in vitro. METHODS: Human lung squamous carcinoma cell line (NCI-H1703), human large-cell lung cancer cell line (NCI-H460), human lung adenocarcinoma cell line (A549) and human fibrosarcoma cell line (HT1080) were tested. Cell viability was detected with MTT assay. Cell migration and invasion were assessed using a wound healing assay and a transwell chemotaxis chambers assay, respectively. Cell apoptosis was analyzed with flow cytometric analysis. The levels of apoptosis-related and metastasis-related proteins were detected by Western blot and immunofluorescence. RESULTS: PTF dose-dependently inhibited the viability of the 3 human lung cancer cells. The IC50 values of PTF in inhibition of NCI-H1703, NCI-H460, and A549 cells were 33, 203, and 94 mg/L, respectively. PTF (15, 30, and 60 mg/L) dose-dependently induced apoptosis of NCI-H1703 cells. Treatment of NCI-H1703 and HT1080 cells with PTF significantly inhibited cell migration, and reduced the number of invasive cells through Matrigel. Furthermore, PTF dose-dependently down-regulated the expression of phosphor-ERK1/2, MMP-2 and MMP-9, up-regulated the expression of phosphor-JNK, but had no significant effect on the expression of ERK1/2 or JNK. CONCLUSION: PTF induces cell apoptosis and inhibits the migration and invasion of NCI-H1703 cells by decreasing MPPs expression through regulation of the MAPK pathway.

[Study on preventive and therapeutic effects of combined application of yindanxinnaotong soft capsule and exercise on atherosclerotic rats].

To explore the prevention effect of the joint combination of Yindanxinnaotong soft capsule (YDXNT) and exercise (swimming) on atherosclerotic rats. The method of 3 x 3 factorial design, including two factors (YDXNT and swimming) and three levels (0, 1, 2 g x kg(-1) YDXNT; 0, 0.5, 1 h swimming), was mainly adopted. The atherosclerotic rat model was established by ligating their left common carotid arteries and feeding high-fat diet. After 8 weeks, blood samples were collected from their thoracic aorta to determine blood viscosity, plasma viscosity, fibrinogen (FIB), nitric oxide (NO), 6-keto-PGF(1alpha) endothelin (ET) and thromboxane B2 (TXB2). The tissues of left common carotid arteries of the rats were collected to detect the positive expression of SM22alpha and determine the semi-quantitation through the immunohistochemical staining. The result showed that the combination of YDXNT and swimming can significantly decrease the plasma viscosity (F = 3.241, P = 0.017), the high and low shear blood viscosity (F = 6.444, P = 0.001; F = 3.002, P = 0.024) and FIB (F = 4.046, P = 0.005). The increased NO and 6-keto-PGF(1alpha) and the decreased ET and TXB2 indicated a significant interaction (P < 0.05). The swimming showed an obvious main effect in the expression of up-regulated protein SM22alpha (F = 8.088, P = 0.001). The study suggested that the combined administration of YDXNT and swimming could improve the hemorheological parameters of atherosclerotic rats, protect the vascular endothelium, inhibit the vascular remodeling in atherosclerosis and positively prevent the atherosclerosis.

[Protection effect of Yindan Xinnaotong capsule and main compositions compatibility on myocardial ischemia/reperfusion injury].

OBJECTIVE: To study the protected effect of Yindan Xinnaotong capsule (YDXNTC) and main components compatibility on myocardium ischemia/reperfusion injury. METHOD: Global ischemia/reperfusion was adopted to induce myocardial ischemia/reperfusion injury (MIRI) in isolated rat heart. Sprague-Dawley (SD) rats were divided into control, model, YDXNTC, Ginkgo biloba extract (GBE) group, ethanol extract of Salvia miltiorrhiza (SM-E) group, aqueous extract of Salvia miltiorrhiza (SM-H) group, mixed compatibility of other components in YDXNTC (MC), GBE and SM-E compatibility (GSEC), GBE and SM-H compatibility (GSHC), and SM-E and SM-H compatibility (SEHC). During the experiment, electrocardiogram was recorded to observe cardiac arrest time, heart resuscitation time, regaining normal rhythm time, the incidence and duration of arrhythmias (VT/VF). At the end of reperfusion, hearts were arrested and homogenated to assay the activity of superoxide dismutase (SOD), and the content of malondialdehyde (MDA), lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), cardiac troponin I. RESULT: (1) YDXNTC, SM-E, SM-H and MC elevated cardiac arrest time, also reduced rebeating time, restoring normal rhythm time as well as the duration of arrhythmia, but no remarkable impact on VT/VF occurrence. GBE was effective for incidence of VT/VF, also achieved good effect on shortening rebeating time, restoring normal rhythm time and arrhythmia duration. Likewise, obviously reduced rebeating time, restoring normal rhythm time and arrhythmia duration, and evaluated cardiac arrest time were also exhibited in compatibility groups except that no lengthened cardiac arrest time was detected in GSHC. And the incidence of VT/VF was decreased by GSEC. (2) YDXNT, ginkgo biloba extract (GBE), ethanol extract of salvia miltiorrhiza (SM-E), GBE and SM-E compatibility (GSEC), and SM-E and aqueous extract of salvia miltiorrhiza (SM-H) compatibility (SEHC) could improved SOD and decreased MDA level SM-H, mixed compatibility of other elements in YDXNTC (MC) and GBE and SM-H compatibility (GSHC) showed a role on MDA reduction. (3) LDH was declined by YDXNT and SM-H. CK-MB was reduced by GBE, SM-E, SM-H, and GSEC. (4) The release of cTnI was only inhibited by GSEC. CONCLUSION: YDXNTC, primary materials and main components compatibility has a certain protection effect on MIRI, its mechanism may be related to antioxidant and calcium overload reduction.

[Experimental study on anti-atherosclerotic effect of compatibility of active components of danshen and shanzha].

OBJECTIVE: To investigate the effect of active components of Danshen and Shanzha of different matching proportions on atherosclerosis (AS), in the expectation of obtaining the optimum combination method. METHOD: Atherosclerotic rats were fed with high fat diet, and injected with vitamin D3 and ovalbumin. Aqueous extracts of Danshen (DSA) and Shanzha (SZA) and lipophilic extracts of danshen (DSL) were adopted for a low, medium and high-dose orthogonal experiment, to observe the effect of their different matching proportions on lipid level, oxidative stress, endothelial function and inflammatory reaction. The principal component analysis and cluster analysis were adopted for the multi-objective optimization of experimental results. RESULT: Compared with the model group, all of samples with different proportions of DSA, DSL and SZA showed effect in lowering lipid level, scavenging free radicals, reducing endothelial dysfunction and inhibiting inflammation. According to the variance analysis, DSA2-SZA2-DSL1, DSA3-SZA2-DSL1, DSA3-SZA3 -DSL3 and DSA3-SZA1-DSL1 were the optimal proportions for lowering lipid level, scavenging free radicals, reducing endothelial dysfunction and inhibiting inflammation, respectively. According to the results of the multi-objective optimization, DSA2-SZA1-DSL2 was the optimal proportions of anti-AS. CONCLUSION: All of active components of Danshen and Shanzha of different matching proportions show the anti-AS effect in rats to varying degrees, but with different focus in different matching proportions.

[LC-MS quantification and pharmacokinetics of the multi-constituents of Huangqin Tang in rat plasma after different single oral doses].

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.

[Determination of endogenous amino acids in brain tissues after cerebral ischemia by RRLC-QQQ].

OBJECTIVE: To establish a method to determine underivatized endogenous amino acids in brain tissues after cerebral ischemia based on RRLC-QQQ. METHOD: Diamonsil chromatographic column C18 (4.6 mm x 250 mm, 5 microm) was adopted to determine 12 amino acids in 15 min, with acetonitrile-0.1% formic acid for gradient elution. The flow rate was set at 0.5 mL x min(-1). With ESI as the ion source, positive ion scanning mode was adopted for multi-reaction monitoring. RESULT: Each amino acid standard curve (AAs) showed good linear relationship within the detection range (r > 0.996), with the limit of detection of less than 11%, the limit of quantitation of less than 3.09 microg x L(-1). The RSD of intra- and inter-day precisions at high, middle and low concentrations were less than 11%. CONCLUSION: The determination results of actual samples showed that compared with the levels of AAs of the sham operation group, all of the remaining amino acids apart from N-acetyl-aspartate increased in brain tissues. Some amino acids showed significant changes in a time-dependent manner after the operation. The method is so simple, rapid and sensitive that it can be used for finding biological metabolite markers of cerebral ischemia, and exploring cerebral ischemia molecular mechanisms and synergistic mechanism of combined administration of multi-component traditional Chinese medicines.

[Pharmacokinetic study on three main ingredients of refined coronary cataplasm].

OBJECTIVE: To establish a LC-MS/MS method for determining the concentration of tanshinone IIA, salvianolic acid B and paeoniflorin of refined coronary cataplasm in rabbit plasma, in order to determine the concentration of the three main ingredients in blood after transdermal administration and calculate their pharmacokinetic parameters. METHOD: Rabbits were given refined coronary cataplasm on the basis of 15 g x kg(-1) by transdermal administration to detect the plasma concentration of the three main ingredients using LC-MS/MS. Winnonlin software was used to calculate their major pharmacokinetic parameters. RESULT: Tanshinone IIA, salvianolic acid B and paeoniflorin showed good linearity (r>0.999) at 1-100, 50-1 000, 10-1 000 microg x L(-1) respectively in plasma, with average recovery rate of 96.57%, 91.90%, 95.93%, respectively. The RSD within day were less than 15%. After transdermal administration of refined coronary cataplasm in rabbits, the main pharmacokinetic parameters of tanshinone IIA, salvianolic acid B or paeoniflorin were as follows: Cmax (20.85 +/- 12.68), (636.25 +/- 386.91), (787.80 +/- 395.64) microg x L(-1); Tmax (0.49 +/- 0.28), (0.44 +/- 0.27), (0.46 +/- 0.30) h. CONCLUSION: The LC-MS/MS method is highly selective and sensitive to determine the concentration of samples in rabbit plasma. The pharmacokinetic characteristics of tanshinone IIA, salvianolic acid B and paeoniflorin are suitable to assess the percutaneous absorption of refined coronary cataplasm.

[Study on compound compatibility of Jinglingzi powder based on absorption-metabolism model].

OBJECTIVE: To establish an absorption-metabolic model suitable for studying the complex traditional Chinese medicine (TCM) system, with the classic Jinlingzi Powder formula as the example, in order to explore the correlation among absorption behavior and absorption-metabolism behavior of different Jinlingzi Powder formulas and their compound compatibility. METHOD: An absorption-metabolic model suitable for TCM study was established according to in vivo characteristics of drugs, to combine the intestinal absorption model with the liver microsomal metabolism model. A quantitative analysis was conduced for absorbable components of Jinlingzi Powder and its absorption-metabolism components by HPLC. RESULT: The model could be used for studies on the absorption-metabolism process of TCM. Among the 15 main components which were derived from Jinlingzi Powder extracts, 10 could be absorbed by intestinal tract. A new component peak was shown after metabolism with the A-M model. The absorbable components of Jinlingzi Powder were related to its compatibility. Toosendan was found to be the major factor impacting the main component-absorption ratio (Ar) and absorption-metabolism ratio (Mr), followed by Rhizoma Corydalis. CONCLUSION: The absorption-metabolism model suitable for studying the complex traditional Chinese medicine system was established and used for the study on compound compatibility of Jinglingzi Powder. The compatibility of the formula has an impact on absorbable component ratio of Jinlingzi Powder, which helps interpret the theory of formula compatibility from the angle of in vitro compound pharmacokinetics (the difference between absorption and metabolism). Toosendan is the main factor impacting overall absorption and absorption-metabolism, while Rhizoma Corydalis is the minor factor.

Bioactive polar compounds from stem bark of Magnolia officinalis.

Two new phenylethanoid glycosides magnoloside D (1) and E (2), together with nine known compounds, were isolated from the polar part of methanol extract of the stem bark of Magnolia officinalis. The structures of the new compounds were established on the basis of spectral analysis. Anti-spasmodic activity of four major constituents (3, 4, 9 and 11) was tested in isolated colon of rat, compounds 3, 4, and 9 showed inhibition against acetylcholine, with the effect similar to that of magnolol and honokiol. At the same time, antioxidant activity of the isolated compounds was investigated using a DPPH and an ORAC assay. All of the compounds, except compound 8 showed potent antioxidant capacity in the ORAC assay, while compounds 1-5 and 11 exhibited potent antioxidant activity in the DPPH assay.

[Relationship between antioxidant activities and contents of active ingredients in Radix Scutellaria].

OBJECTIVE: To study the relationship between the antioxidant activities and the contents of active ingredients in Radix Scutellaria. METHOD: The antioxidant activities of extracts and active ingredients of Radix Scutellaria in NADPH-dependent lipid peroxidation in rat liver microsome were assayed. RESULT: Extracts of Radix Scutellaria showed a 50% inhibition of lipid peroxidation in the concentration range of 2.72-18.27 mg x L(-1). CONCLUSION: The antioxidant activities of extracts of Radix Scutellaria are not only related with the contents but also the ratio of the active ingredients.

[Effect of prim-o-glucosylcimifugin and 4'-O-beta-D-glucosyl-5-O-methylvisamminol con on proliferation of smooth muscle cell stimulated by TNF-alpha].

OBJECTIVE: To investigate the effect of prim-O-glucosylcimifugin and 4'-O-p-D-glucosyl-5-O-methylvisa-mminol con on the proliferation of smooth muscle cell stimulated by TNF-alpha. METHOD: The primary cell culture method of smooth muscle cell (SMC) was established by attachment-block. The SMC was identificated by immunochemistry method, and the growth curve was drawn by cytometry. The third generation of SMC was adopted in the experiment. The effect of prim-O-glucosylcimif-ugin and 4'-O-beta-D-glucosyl-5-O-methylvisamminol con on the proliferation and cell cycle of SMC was investigated by MTT and flow cytometry respectively. RESULT: TNF-alpha of 5 micro g x L(-1) can stimulate the proliferation of SMC and increase the proportion of G2 phase and S phase in cell cycle which has great significant difference (P < 0.01) compared with control. The three dose groups of prim-O-glucosylcimifugin and 4'-O-beta-D-glucosyl-5-O-methylvisammin-ol con can inhibit the proliferation of SMC and increase the proportion of G0/G1 phase, which has great significant difference (P < 0.01) compared with model group. CONCLUSION: Prim-O-glucosylcimifugin and 4'-O-beta-D-glucosyl-5-O-methylvisamminol con can inhibit the proliferation of SMC stimulated by TNF-alpha.