Efficacy of Yangyin Yiqi Huoxue Granule () in Treatment of Ischemic Stroke Patients with Qi-Yin Deficiency and Blood Stasis Syndrome: A Randomized, Double-Blind, Multicenter, Phase-2 Clinical Trial / 中国结合医学杂志

OBJECTIVE@#To evaluate the efficacy and safety of Yangyin Yiqi Huoxue Granule (, YYHG) in the treatment of ischemic stroke (IS) patients with qi-yin deficiency and blood stasis syndrome (QYDBSS), and to explore its effective dosage.@*METHODS@#The total of 288 patients were randomly assigned to the YYHG high-dose, YYHG low-dose, positive control (administered Xiaoshuantong Granule, XSTG, ), or placebo control (administered inert granule) groups (72 cases per group) by software-drived competitive block randomization. The trial was conducted for a 28-day period, with a 180-day follow-up period. The primary outcome was the comprehensive curative evaluation, and secondary outcomes were the National Institute of Health Stroke Scale (NIHSS) score, Barthel activities of daily living (ADL) index score, the quality of life index (QLI) score, and the Chinese medicine syndrome (CMS) score. All analyses were done on an intention-to-treat basis. The clinical safety was also assessed.@*RESULTS@#The total of 288 participants were recruited between June 1, 2008 and September 30, 2009, and 287 patients received intervention; the treatment groups were well balanced at baseline. The comprehensive cure rates of YYHG high-dose, low-dose, positive and placebo control groups were 63.38%, 31.94%, 36.11% and 6.14%, respectively; there was a statistical difference between the two groups (P<0.01), while the high-dose YYHG treatment group was significantly higher than the other 3 groups (P<0.01). The improvement of NIHSS, ADL, QLI and CMS scores of the YYHG high-dose and low-dose groups was significantly better than that of the positive control group and the placebo control group (P<0.05). In terms of improving the classification of the NIHSS scale and the assessment of the ADL scale, the YYHG high-dose group was significantly better than the other three groups (P<0.05), and the YYHG low-dose group was better than the placebo control group (P<0.01). At the same time, except for the QLI score, the high-dose group was better than the low-dose group (P<0.05). In terms of safety, adverse reactions after YYHG treatment were generally mild (3.78%), and no serious adverse reactions have been reported.@*CONCLUSION@#YYHG is safe and effective in the treatment of IS patients with QYDBSS.

Protective Effect of Naoxintong Capsule () Combined with Guhong Injection () on Rat Brain Microvascular Endothelial Cells during Cerebral Ischemia-Reperfusion Injury / 中国结合医学杂志

OBJECTIVE@#To investigate the synergistic effect of Naoxintong Capsule (NXTC, ) and Guhong Injection (GHI, ) on cerebral ischemia-reperfusion (I/R) injury.@*METHODS@#Forty-eight Sprague-Dawley rats were divided into 6 groups: control group, oxygen and glucose deprivation (OGD) group, nimodipine group (9.375 mg/kg), NXTC group (0.5 g/kg), GHI group (5 mL/kg) and NXTC+GHI group (0.5 g/kg NXTC+5 mL/kg GHI), after the onset of reperfusion and once per day for the following 7 days. Blood was collected 1 h after final administration, and the sera were collected. Cultured primary rat brain microvascular endothelial cells (rBMECs) were subjected to OGD to establish a cell injury model. Untreated rBMECs were used as blank control. The cell counting kit-8 assay was used to assess cell viability using the sera. Malondialdehyde (MDA) and superoxide dismutase (SOD) levels were assessed using an enzyme-linked immunosorbent assay. Apoptosis was evaluated after Hoechst33342 staining using fluorescence microscopy and flow cytometry. JC-1 staining was performed to assess changes in mitochondrial membrane potential.@*RESULTS@#Statistical analysis indicated that more than 95% of the cells were rBMECs. Compared with the OGD group, the cellular morphology of the all drug delivery groups improved. In particular, the combined drug group had the most significant effect. Compared with the OGD group, all drug intervention groups induced a decrease in the apoptotic rate of rBMECs, increased the SOD levels, and decreased the MDA levels (all P<0.01). Compared with the mono-therapy groups, the NXTC+GHI group exhibited a significant improvement in the number of apoptotic rBMECs (P<0.01). All drug intervention groups showed different degrees of increase in membrane potential, and the NXTC+GHI group was higher than the NXTC or GHI group (P<0.01).@*CONCLUSION@#The combinationa application of NXTC and GHI on cerebral I/R injury clearly resulted in protective benefits.

Lipid-lowering effect and mechanism of Danhong Injection on hyperlipidemia rats based on lipid metabolism disorder / 中国中药杂志

The animal model of hyperlipidemia in rats was established to investigate the lipid-lowering effect and mechanism of Danhong Injection on hyperlipidemic rats. SD rats were selected as the research object. The rats in normal group were fed with basic diet, and the rats in other groups were fed with high-fat diet to establish hyperlipidemia model. The successfully modeled rats were randomly divided into model group, Danhong Injection low, medium, high dose(1.0, 2.0, 4.0 mL·kg~(-1)) groups, and simvastatin(2.0 mg·kg~(-1)) group. Danhong Injection groups received intraperitoneal administration, and simvastatin group received intragastrical administration, once a day for 4 weeks. At the first, second, third, and fourth weekends after administration, blood was collected from the orbital vein to detect the levels of total cholesterol(TC), triglyceride(TG), low-density lipoprotein cholesterol(LDL-C), and high-density lipoprotein cholesterol(HDL-C), and then the atherosclerosis index(AI) was calculated. After 4 weeks of administration, the animals were sacrificed, and their heart, liver, spleen, lung, kidney and adipose tissue were extracted and weighed respectively to calculate the organ index of each group. The expressions of acyl-coaoxidase 1(Acox1), adenosine 5'-monophosphate(AMP)-activated protein kinase alpha(AMPK-α), bile salt export pump(BSEP), peroxisome proliferator-activated receptor gamma(PPAR-γ), catalase(CAT) and superoxide dismutase(SOD) mRNA in liver tissues were detected by fluorescence quantitative PCR; the content of cholesteryl ester transfer protein(CETP) and lecithin cholesterol acyltransferase(LCAT) in serum was detected by ELISA. The results showed that as compared with the normal group, the levels of serum TC, TG and LDL-C in the model group were significantly increased, and the level of HDL-C was significantly decreased, indicating that the hyperlipidemia rat model was successfully constructed. As compared with the model group, Danhong Injection could decrease the contents of TC, TG, LDL-C and increase the content of HDL-C in hyperlipidemia rats; reduce the body weight of hyperlipidemia rats, and reduce the liver weight, liver index, fat weight and fat index; it had no significant effect on the main organ indexes such as heart, spleen, lung and kidney; but it could increase the expressions of Acox1, AMPK-α, BSEP, PPAR-γ, CAT and SOD mRNA in liver tissues of rats; it could also reduce the level of CETP and increase the level of LCAT in serum; and the regulatory effect of Danhong Injection groups all showed a dose-dependent effect. It can be concluded that Danhong Injection can regulate the blood lipid contents, reduce the blood lipid levels and alleviate the accumulation of body fat in rats with hyperlipidemia. The mechanism may be related to inhibiting lipid metabolism disorder and oxidative stress induced by high-fat diet feeding, and improving the imbalance of lipid transport system.

Pharmacokinetics of compatible effective components of Mahuang Decoction in febrile rats / 中国中药杂志

In the present paper,after the febrile rat model was prepared by injecting yeast,orthogonally compatible effective components from prescription drugs of Mahuang Decoction( Ephedra sinica total alkaloids,Cinnamomum cassia essential oil,amygdalin,Glycyrrhiza uralensis total flavonoids+G. uralensis total saponins) with nine different dosage ratios were given by gavage administration.The plasma concentrations of main active ingredients including ephedrine hydrochloride,pseudoephedrine hydrochloride,methylephedrine hydrochloride,cinnamic acid,amygdalin,liquritin and glycyrrhizin at different time points were analyzed by liquid chromatograph mass spectrometer( LC-MS). Based on the pharmacokinetic parameters of non-compartmental model,the area under curve of total quantum( AUCt) and the mean chromatographic retention time of total quantum( MRTt) were further calculated,in order to evaluate the effect of compatibility on the total statistical moment parameters. The results showed that the pharmacokinetic characteristics of main active components in febrile rats were significantly different after treatment with orthogonally compatibility of E. sinica total alkaloids,C.cassia essential oil,amygdalin,G. uralensis total flavonoids and G. uralensis total saponins. Orthogonal analysis confirmed that different compatibility components had different effects on the total statistical moment parameters. The contribution of effective components of Mahuang Decoction to AUCtwas as follows in a descending order: E. sinica total alkaloids>C. cassia essential oil>amygdalin>G. uralensis total flavonoids+G. uralensis total saponin,while the contribution to MRTtwas: E. sinica total alkaloids >G. uralensis total flavonoids+G. uralensis total saponin>amygdalin>C. cassia essential oil. The E. sinica total alkaloid had the greatest effects on both of the above parameters,and the optimal combination was A_3B_3C_2D_1 for AUCt,and A_1B_1C_1D_1 for MRTt.

Protective effect and mechanism of total anthraquinone extract of Rhei Radix et Rhizoma on cerebral ischemia-reperfusion injury / 中成药

AIM To investigate the effect and mechanism of total anthraquinone extract of Rhei Radix et Rhizoma on cerebral ischemia-reperfusion injury and to provide relevant data references for its promising use in the management of cerebral ischemia-reperfusion injury.METHODS SD rats randomly assigned to model group,sham operation group,nimodipine group,total anthraquinone extract groups (high,medium and low dose),8 in each group,were orally administered with corresponding drugs daily for a week,with rats of the model group and sham operation group given the same volume of normal saline before the models established by middle cerebral artery occlusion (MCAO).MCAO started thirty minutes after final oral administration,and the induced ischemia went on for 1.5 h for a further reperfusion,24 h after which the neurological function score,brain index,brain water content and cerebral infarct volume were measured.Elisa kits were used to detect superoxide dismutase (SOD),Malondialdehyde (MDA),Nitric oxide (NO),interleukin-1 β (IL-1β),tumor necrosis factor (TNF),interleukin-6 (IL-6).RESULTS The total anthraquinone extract of Rhei Radix et Rhizoma significantly improved the neurological function score,decreased the brain index,brain water content,reduced the cerebral infarct volume (P ＜ 0.05),increased the activity of SOD in brain tissue (P ＜ 0.01),and reduced the levels of MDA and NO in brain tissue (P ＜0.01),and the levels of IL-6,TNF and IL-1β in serum (P ＜0.01) as well.CONCLUSION The obviously protective effect on rats' cerebral ischemia-reperfusion injury by total anthraquinone extract of Rhei Radix et Rhizoma may contribute to its inhibition of inflammatory response,and its existence as an antioxidant as well.

Effect of Danhong injection on AMPK/SREBP-1/ACC pathways of liver in hyperlipidemic rats / 中国药理学通报

Aim To discuss the effect of Danhong in-jection(DHI) on hyperlipidemia in rats and its possible mechanism. Methods The hyperlipidemia model of rats were induced by high fat diet. The protein expres-sion of adenosine 5'-monophosphate-activated protein kinase(AMPK), p-AMPK, cholesterol-binding ele-ment binding protein (SREBP-1), adenylate-activated protein kinase carboxylasecetyl-CoA(ACC) and p-ACC in liver were detected using Western blot. Results The protein expression levels of AMPK, SREBP-1 and ACC significantly decreased (P<0.05), but the pro-tein expression levels of p-ACC and p-AMPK signifi-cantly increased (P<0.05). Conclusions Danhong injection can reduce the activity of SREBP-1 and ACC by enhancing the activation of AMPK, and effectively reduce the blood lipid level of hyperlipidemic rats by promoting fatty acid oxidation and reducing lipid depo-sition.

Pharmacokinetics of main activ ingredients of Guhong injection in cerebral ischemia rats / 中国中药杂志

To investigate the pharmacokinetic characteristics of active constituents of Guhong injection in rats with cerebral ischemia reperfusion injury. The middle cerebral artery occlusion (MCAO) model was established in our studies, and then all the rats received iv administration of Guhong injection (2.1 mL·kg⁻¹). The blood concentrations of aceglutamide and hydroxysafflor yellow A (HSYA) were determined by high performance liquid chromatography (HPLC) method at different time points. The concentration-time curves were drawn and pharmacokinetic data were obtained by DAS 3.2.6 software. The results showed that aceglutamide and HSYA showed good linear relationship within the ranges of 1.5-500 mg·L⁻¹ (R²=0.997 5) and 0.33-40 mg·L⁻¹ (R²=0.998 9) respectively. This quantitative method showed a high recovery rate, good precision and stability. The main pharmacokinetics parameters of t1/2α, t1/2β, CL₁, CL₂, AUC0-t, AUC0-∞, Vd1, and Vd2 were (0.139±0.007) and (0.155±0.017) h, (0.803±0.046) and (2.233±0.410) h, (0.016±0) and (0.149±0.018) L·h⁻¹·kg⁻¹, (0.015±0.001) and (0.446±0.016) L·h⁻¹·kg⁻¹, (133.335±3.844) and (9.298±0.179) mg·h·L⁻¹, (143.851±3.595) and (14.464±1.451) mg·h·L⁻¹, (0.009±0.001) and (0.223±0.007) L·kg⁻¹, (0.006±0.001) and (0.212±0.032) L·kg⁻¹, respectively. The results showed that the established HPLC method was highly specific, and could be used for the simultaneous detection of aceglutamide and HSYA of Guhong injection in MCAO rats, which was conducive to pharmacokinetic studies. Pharmacokinetic data and parameters could provide reference for continuous administration and interval administration of the drug.

Immunologic mechanisms of Yinhua Pinggan granule and San-ao decoction against influenza virus / 中国中药杂志

This paper aimed to investigate the effect of Yinhua Pinggan granule and San-ao decoction on the immunologic mechanisms of influenza viral pneumonia mice , in order to study the activity of the combined administration of different formulas on influenza A/H1N1 virus. The model of pneumonia was established in mice through nasal dropping influenza virus, and then divided randomly into five groups: normal control group, influenza virus model group, oseltamivir control group, Yinhua Pinggan granule group, and San-ao decoction group. The animals were put to death at the 5th day after gavage administration with the corresponding drugs. The contents in mice serum of TNF-α, IL-6 and IFN-γ were respectively measured by ELISA. The mRNA expressions of TLR3/7, MyD88, JNK, p38MAPK and NF-κB p65 in lung tissues were respectively detected by RT-PCR. The protein expressions of JNK, p38MAPK and NF-κB p65 in lung tissues were determined by immunohistochemical analysis, respectively. According to the results, Yinhua Pinggan granule and San-ao decoction could significantly decrease the levels of TNF-α and IL-6, increase the level of IFN-γ in mice serum of lung tissues, significantly reduce the gene expressions of TLR3/7, MyD88, JNK, p38MAPK and NF-κB p65 in influenza virus-infected mice lung tissues, and significantly reduce the protein expressions of JNK, p38MAPK and NF-κB p65 in lung tissues. Furthermore, the regulatory effect of Yinhua Pinggan granule was superior to that of San-ao decoction. In conclusion, Yinhua Pingan granule and San-ao decoction have the therapeutic effect on pneumonia mice infected by H1N1 virus . The anti-influenza mechanisms of Yinhua Pinggan granule and San-ao decoction may be the results of interactions by regulating the immunologic function of influenza virus-infected mice and TLR3/7 signaling pathway with multiple links of the gene and protein expressions. Moreover, the combined administration of warm-natured and cold-natured Yinhua Pinggan granule with the effects of detoxification and exhalation has a better effect than the single administration of warm-natured San-ao decoction.

Effect and mechanism of Mahuang Tang against influenza A/H1N1 virus / 中国中药杂志

To study the effect and underlying mechanism of Mahuang Tang against influenza A virus ， the influenza virus-infected Madin-Darby canine kidney(MDCK) cells were used as the carrier in this study to detect the median tissue culture-infective dose(TCID₅₀) of influenza A virus strains(A/PR8/34) on MDCK cells with cytopathic effect(CPE) assay. Blocking influenza virus invading host cells and anti-influenza virus biosynthesis were used as two different administration methods， and then the methyl thiazolyl tetrazolium(MTT) assay was utilized to determine the antiviral effective rate(ER)， median efficacious concentration(EC₅₀) and therapeutic index(TI) of Mahuang Tang. The quantitative Real-time polymerase chain reaction(RT-PCR) was used to measure virus load and the mRNA expression levels of TLR4， TLR7， MyD88 and TRAF6 in MDCK cells at 24， 48 h after the treatment. The experiment results indicated that TCID₅₀ of A/PR8/34 for MDCK cells was 1×10-4.32/mL. The EC₅₀ values of two different treatment methods were 4.92，1.59 g·L⁻¹ respectively， the TI values were 12.53， 38.78 respectively， and when the concentration of Mahuang Tang was 5.00 g·L⁻¹， ER values were 50.21%， 98.41% respectively， showing that Mahuang Tang can block influenza virus into the host cells and significantly inhibit their biosynthesis. Meanwhile， as compared with the virus group， the virus load was significantly inhibited in Mahuang Tang groups， and Mahuang Tang high and middle doses had the significant effect on decreasing the mRNA expression of TLR4， TLR7，MyD88 and TRAF6 at 24， 48 h after the treatment. It can be demonstrated that the mechanisms of Mahuang Tang against influenza A virus are related to the inhibition of influenza virus replication and the mRNA expression of correlative genes in TLR4 and TLR7 signaling pathways.

Experimental Study on the Protection of Agrimony Extracts from Different Extracting Methods against Cerebral Ischemia-Reperfusion Injury / 中国医学科学杂志(英文版)

Objective To study the protective effect of agrimony extracts from different extracting methods on cerebral ischemia-reperfusion injury in rats, in order to optimize the extraction scheme of agrimony. Methods Male rats were randomly assigned into seven groups: 1. Sham-operated group, 2. Untreated MCAO group (MCAO), 3. Petroleum ether extract of Agrimonia pilosa treated MCAO group (PEA), 4. Ethyl acetate extract of Agrimonia pilosa treated MCAO group (EAEA), 5. Ethanol extract of Agrimonia pilosa treated MCAO group (EEA), 6. Water extract of Agrimonia pilosa treated MCAO group (WEA), 7. Nimodipine treated MCAO group (NP). Intragastrical drug administration (i.g) was performed at 0 and 6 hours after MCAO. Neurological function tests were performed after reperfusion for 24 hours, then the brain was removed for the evaluations of the cerebral infarction volume (percentage of total brain volume) by immunohistochemistry, histological changes (hematoxylin-eosin staining), Na/K-ATPase, Ca-ATPase (modified method of Svoboda and Mosinger), mRNA expression of Tumor suppressor gene (P53) and hot shock protein (HSP70) (quantitative real-time PCR). Results The neurological function of MCAO group had significantly higher scores than the sham group (P<0.01). The WEA group showed a significantly lower neurological score than the MCAO group (P<0.05), indicating the protective effect of WEA on neurological deficits. The mean infarction volumes of WEA (13.5±6.6%, F=4.75, P<0.01), EEA (19.90±6.90%, F=5.23, P<0.01), PEA (20.40±5.30%, F=4.68, P<0.01) and EAEA (22.50±10.50%, F=6.25, P<0.05) group were all significantly smaller than that of MCAO group (29.40±6.50%). HE staining demonstrated that, compared to the treated groups, the infarcted cerebral tissue of MCAO group had more swelling neural cells, lighter stained nucleus, fewer and irregularly distributed neurons. The activity of Na/K-ATPase and Ca-ATPase reduced in the MCAO group (3.67±0.48 U/mg, 1.28±0.26 U/mg, respectively), and were significantly higher in WEA group (7.56±0.85 U/mg, F=12.65, P=0.010; 3.59±0.22 U/mg, F=8.32, P=0.041, respectively). The MCAO group showed significantly elevated P53 and HSP70 mRNA expressions compared to the sham group (P<0.01, P<0.05). P53 mRNA expressions in Agrimony extracts treated groups were significantly lower than that of the MCAO group (all P<0.01), with the WEA group showing the greatest difference from MCAO group. The HSP70 mRNA level of the treated groups were not significantly different from that of the MCAO group. Conclusions Treatment using water extracts of agrimony can promote the best functional and metabolic recovery for rat model of cerebral ischemia-reperfusion injury, which maybe relate with the upregulation of energy metabolism in nerve cells after MCAO.

Effects of Danhong Injection (丹红注射液) and its main components on anticoagulation and fibrinolysis in cultured vein endothelial cells / 中国结合医学杂志

<p><b>OBJECTIVE</b>To observe the effects of Danhong Injection (丹红注射液) and its main components, including daiclzein and hydroxysafflor yellow A (HSYA), on the anticoagulation, fibrinolysis, anti-apoptosis in hypoxia model of vein endothelial cells (VECs).</p><p><b>METHODS</b>VECs were prepared and were put in a hypoxia environment, which consisted of mixed gas of 95% N and 5% CO mixed gas, when reached confluent culture. Five groups used different treatments, including normal control group, hypoxia group, daiclzein group, HSYA group and Danhong Injection group. The VECs were identified by fluorescence double labeling methods. The morphology was observed by a phase contrast microscopy. The effects of Danhong Injection, daiclzein and HSYA on 6 keto prostaglandin F1α (6-keto-PGF1α) level was measured by the method of radioimmunoassay (RIA). Superoxide dismutase (SOD) activity was tested by water soluble tetrazolium salt. The content of malondialdehyde (MDA) was measured by thiobarbituric acid. The activities of tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI) were measured by the method of chromogenic substrate. The contents of endothelin (ET) and nitric oxide (NO) were detected by non-equilibrium RIA and enzymelinked immunosorbent assay. Cells apoptosis rate was determined by flow cytometry.</p><p><b>RESULTS</b>Compared with the normal control group, the floating cells number, PAI activity, ET and MDA contents, and cells apoptosis rate in the culture solution of hypoxia group were all significantly increased, whereas the 6-keto-PGF1α and NO contents, and t-PA and SOD activities were decreased significantly (P<0.01). Compared with the hypoxia group, Danhong Injection markedly increased the 6-keto-PGF1α content and SOD activity, regulated PAI and t-PA activities, ET and NO contents, and decreased MDA content and cells apoptosis rate (P<0.05 or P<0.01).</p><p><b>CONCLUSIONS</b>Danhong Injection and its main components played an important role in protecting primary VECs from hypoxic damage by regulating the secretion and vasomotor function of VECs. The function of Danhong Injection was most remarkable.</p>

Pharmacokinetic and pharmacodynamic analysis of ferulic acid-puerarin-astragaloside in combination with neuroprotective in cerebral ischemia/reperfusion injury in rats

Objective: To investigate the effects of the active ingredients combined therapy on inflammatory factors interleukin 1 beta (IL-1β) and neuropeptide Y (NPY) based on pharmacodynamics in rats. Methods: The animal model was built by transient middle cerebral artery occlusion (MCAO). The method for evaluating the concentrations of the FA-Pr-Al components in rat plasma was established by using HPLC and the expression levels of IL-1β and NPY were determined by ELISA. A new mathematics method of the trend of percentage rate of change (PRC) was used to assess the correlation between pharmacokinetics (PK) and pharmacodynamics (PD). Results: FA-Pr-Al in combination reduced neurological deficits, decreased infarct volume and inhibited the expression levels of IL-1β and NPY (all Pmax was reached. Astragaloside's PRC value was significantly higher than those of FA and puerarin between 120 to 180 min. Conclusions: The pharmacokinetics of FA-Pr-Al in combination were closely related its pharmacodynamics in treating ischemia/reperfusion injury, and the components of FA-Pr-Al may have a synergistic pharmacological effect. Astragaloside may play a more pronounced role in regulating IL-1βand NPY levels compared with puerarin or FA.

Effect of Shenxiong injection on inflammation injury of ischemia-reperfusion injury rats / 中国中药杂志

To investigate the effect of Shenxiong injection on the inflammation injury of ischemia-reperfusion injury senile rats. Totally 84 Sprague-Dawley (SD) rats were randomly divided into six groups: the sham operation group, the model group, the Nimodipine group and the Shenxiong injection(low, middle, and high dosage) groups. The rat cerebral ischemia-reperfusion model was established through intraperitoneal injection for 3 d and middle cerebral artery occlusion (MCAO). Ater the reperfusion for 24 h, efforts were made to give neurological score, collect brains for TTC staining, detect tumor necrosis factor-α(TNF-α) and interleukin-1β(IL-1β) content in serum by enzyme-linked immunosorbent assay (ELISA) method and measure IL-1β, ICAM-1 and MMP-9 mRNA expressions in hippocampal area by Real-time PCR (RT-PCR). According to the results, Shenxiong injection could decrease the cerebral infarction volume, greatly improved the neurological function and reduce IL-1β, TNF-α, ICAM-1 and MMP-9 mRNA expressions and IL-1β and TNF-α contents. In conclusion, Shenxiong injection shows the significant protective effect on ischemia-reperfusion injury in rats. Its mechanism may be related to the inhibition of inflammatory factor expression.

In vitro microdialysis recoveries of nine active ingredients in Mahuang decoction / 中国中药杂志

To detect the in vitro probe microdialysis recoveries based on an HPLC-DAD method for simultaneous quantification of nine active ingredients (ephedrine, pseudoephedrine, methylephedrine, amygdalin, liquiritin, cinnamyl alcohol, cinnamic acid, cinnamaldehyde and glycyrrhizic acid) in Mahuang decoction, which provides reference for in vivo pharmacokinetic study. The concentrations of nine active ingredients in dialysate were detected by HPLC-DAD, to investigate the effect of flow rates (incremental method and subtraction method) and intraday stability of the probe recoveries and medium concentrations on the recoveries. Nine active ingredients could be well separated in 52 min. At the perfusion rate of 1.0 μL x min(-1), the relative recoveries of ephedrine, pseudoephedrine, methylephedrine, amygdalin, liquiritin, cinnamyl alcohol, cinnamic acid, cinnamaldehyde and glycyrrhizic acid were (50.95 ± 0.82)%, (52.74 ± 1.13)%, (51.29 ± 0.51)%, (32.56 ± 0.84)%, (45.36 ± 0.83)%, (70.94 ± 0.99)%, (69.98 ± 2.30)%, (71.68 ± 0.63)%, and (22.14 ± 0.48)%, respectively. And the probe kept steady in 7 hours. At the same medium concentration, the probe recoveries decreased exponentially with the increase in flow rates. The recoveries of seven ingredients detected by these two methods were similar at certain flow rates, except for amygdalin and cinnamaldehyde. At the same flow rate, the relative recoveries of cinnamyl alcohol, cinnamic acid and cinnamaldehyde changed greatly (9.55%-16.2%) and the others six ingredients had less change (3.27%-5.71%) with the changes in medium concentrations. Microdialysis method could be used to detect the in vitro recoveries of nine ingredients in Mahuang decoction. Reverse dialysis method could be used for the in vivo probe recovery calibration of ephedrine, pseudoephedrine, methylephedrine, liquiritin, cinnamyl alcohol and cinnamic acid at the flow rate of 2.0 μL x min(-1).

Effect of Yinghua Pinggan granule against influenza A/H1N1 virus in vivo / 中国中药杂志

To study the effect of Yinghua Pinggan granule (YHPG) against influenza A/H1N1 virus in vivo and on the immunologic function of infected mice. The intranasal influenza virus infection was adopted in ICR mouse to establish the influenza virus pneumonia model. At the 3rd and 7th day after the infection, the lung index and pathologic changes in lung tissues of mice were detected. Realtime PCR and flow cytometry were employed to observe the virus load in lung tissues and the levels of CD4+, CD8+, and CD4+/CD8+ in peripheral blood. The result showed that at the 3rd and 7th day after the infection, YHPG (15, 30 g x kg(-1)) can significant decrease in the lung index and virus load in lung tissues of mice infected with influenza virus, alleviate the pathologic changes in lung tissues, significantly increase the levels of CD4+ and CD4+/CD8+ ratio and reduce the levels of CD8+ in whole blood. This indicated that YHPG can inhibit the influenza virus replication, alleviate pulmonary damage and adjust the weak immunologic function of infected mice, with a certain therapeutic effect on mice infected by H1N1 virus in vivo.

Treating ischemic stroke patients of deficiency of qi and yin syndrome and static blood obstructing collaterals syndrome by Yangyin Yiqi Huoxue Recipe: a clinical study of therapeutic effect / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the clinical effect of Yangyin Yiqi Huoxue Recipe (YYHR, the basic recipe of Yangyin Tongnao Granule) in treatment of ischemic stroke patients of deficiency of qi and yin syndrome (DQYS) and static blood obstructing collaterals syndrome (SBOCS).</p><p><b>METHODS</b>Totally 312 patients were assigned to the control group (86 cases) and the treatment group (226 cases) using strati- fied randomized allocation method. Patients in the treatment group were treated with modified YYHR, while those in the control group took Xueshuan Xinmaining. The treatment course was 4 weeks for all. Constituent ratios of the acute stage and the recovery stage of DQYS and SBOCS and their complicated syndromes were observed in the two groups. Changes of the clinical curative effect, clinical symptoms integral, whole blood viscosity ratio, plasma viscosity ratio, hematocrit, erythrocyte sedimentation rate (ESR), total cho- lesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), and low density lipoprotein cholesterol (LDL-C) were detected in the two groups before and after treatment.</p><p><b>RESULTS</b>There was statistical difference in constituent ratios of the acute stage and the recovery stage of DQYS SBOCS and its complicated syndromes between the two groups (P < 0.01). DQYS and SBOCS was basic syndrome types of the two groups. The cured and markedly effective rate was 71.24%(161/226) in the treatment group and 43.02% (37/86) in the control group. The total effective rate was 91.15% (206/226) in the treatment group, higher than that of the control group (76.74%, 66/86) with statistical difference (P < 0.01). There was statistical difference in the clinical symptoms integral, whole blood viscosity ratio, plasma viscosity ratio, hematocrit, ESR, TC, TG,HDL-C, and LDL-C (P < 0.05, P < 0.01).</p><p><b>CONCLUSIONS</b>Symptoms of ischemic stroke patients could be improved by modified YYHR. Indices such as the whole blood viscosity, plasma viscosity ratio, hematocrit, ESR, abnormal metabolism of blood lipids were also significantly improved. Pathological changes of blood stasis induced by qi-yin deficiency exist in ischemic stroke patients, and DQYS and SBOCS were basic syndrome types.</p>

Study on regulatory effect of Danshensu on lipid metabolism of hyperlipidemia rats / 中国中药杂志

<p><b>OBJECTIVE</b>To explore the effect of Danshensu on the lipid metabolism of hyperlipidemic rats.</p><p><b>METHOD</b>Sixty clean male SD rats were selected. Twelve of them were selected in the basic control group and fed with common foods, and the remaining rats were fed with the high-fat feeds. After the successful modeling, they were randomly divided into the high-fat control group and low dose (10 mg x kg(-1) x d(-1)), medium dose (20 mg x kg(-1) x d(-1)) and high dose (40 mg x kg(-1) x d(-1)) Danshensu (dissolved in saline) groups. Both of the two groups were abdominally injected with the same volume of normal saline once a day for consecutively 30 days. The serum TG, TC, HDL-C and liver ACC1, FAS, HMGR, CPT-I mRNA expressions were detected.</p><p><b>RESULT AND CONCLUSION</b>Danshensu could inhibit the LDL-C level, timely clear redundant cholesterol and effectively regulate the lipid metablism of hyperlipidemic rats by reducing the TC content, decrease the fatty acid by reducing the FAS mRNA expression, and reduce the synthesis levels of endogenous cholesterol by inhibit the HMGR mRNA expression.</p>

Pharmacokinetic and pharmacodynamic analysis of ferulic acid-puerarin-astragaloside in combination with neuroprotective in cerebral ischemia/reperfusion injury in rats

OBJECTIVE@#To investigate the effects of the active ingredients combined therapy on inflammatory factors interleukin 1 beta (IL-1β) and neuropeptide Y (NPY) based on pharmacodynamics in rats.@*METHODS@#The animal model was built by transient middle cerebral artery occlusion (MCAO). The method for evaluating the concentrations of the FA-Pr-Al components in rat plasma was established by using HPLC and the expression levels of IL-1β and NPY were determined by ELISA. A new mathematics method of the trend of percentage rate of change (PRC) was used to assess the correlation between pharmacokinetics (PK) and pharmacodynamics (PD).@*RESULTS@#FA-Pr-Al in combination reduced neurological deficits, decreased infarct volume and inhibited the expression levels of IL-1β and NPY (all P<0.05) compared with the model group. FA, Pr and Al all displayed two compartment open models in rats. Clockwise hysteresis loops were obtained by time-concentration-effect curves. IL-1β and NPY level changes in the plasma followed an opposite trend to the plasma concentration tendency after Cmax was reached. Astragaloside's PRC value was significantly higher than those of FA and puerarin between 120 to 180 min.@*CONCLUSIONS@#The pharmacokinetics of FA-Pr-Al in combination were closely related its pharmacodynamics in treating ischemia/reperfusion injury, and the components of FA-Pr-Al may have a synergistic pharmacological effect. Astragaloside may play a more pronounced role in regulating IL-1βand NPY levels compared with puerarin or FA.

Protective effect of combined administration of active ingredients of Danhong on cerebral micro-vascular endothelial cell injured by hypoxia / 中国中药杂志

To study the protective effect of combined administration of active ingredients of Danhong on cultured primary mice's brain microvascular endothelial cells (rBMECs) injured by hypoxia. Primary mice's brain micro-vascular endothelial cells were cultured to establish the 4 h hypoxia model. Meanwhile, active ingredients (protocatechuic aldehyde, salvianolic acid B, hydroxysafflor yellow A and tanshinol) of Danhong were administered in rBMECs. The non-toxic dosage was determined by MTT. The leakage of lactate dehydrogenase(LDH), cell superoxide dismutase (SOD) activity and MDA level were detected by the colorimetric method. The expressions of ICAM-1, MMP-9, P53 mRNA were detected by RT-PCR method. Changes in rBMECs cell cycle and early apoptosis were detected by flow cytometry. Danhong's active ingredients and prescriptions 1, 2, 3, 7, 8, 9 could be combined to significantly restrain LDH in hypoxic cells supernatant. Prescriptions 1, 2, 3, 7, 8, 9 could significantly enhance SOD activity in anoxic cells; Prescriptions 1, 2, 3, 8, 9 could significantly decrease the MDA level; Prescriptions 1, 2, 6, 7, 9 could significantly inhibit the early rB-MECs apoptosis induced by hypoxia. After hypoxia, the up-regulated P53 mRNA expression could cause retardation in G, phase and promote cell apoptosis. This proved that the regulatory function of P53 gene lay in monitoring of calibration points in G, phase. Prescriptions 1, 2, 5, 6, 7, 8, 9 could significantly down-regulate the P53 mRNA expression; Prescriptions 1, 4, 7, 8, 9 could significantly down-regulate the ICAM-1 mRNA expression; Prescriptions 1, 3, 6, 9 could significantly down-regulate the MMP-9 mRNA expression. The combined administration of Danhong's active ingredients showed a significant protective effect on primary cultured rBMECs injury induced by hypoxia Its mechanism may be related to the enhancement of cellular antioxidant capacity and the inhibition of inflammatory response and cell apoptosis. This study could provide ideas for researching prescription compatibility, and guide the clinical medication.

Effect and mechanism of Guhong injection against cerebral ischemia reperfusion injury / 中国中药杂志

To explore the effect and mechanism of Guhong injection against cerebral ischemia reperfusion injury, SD rats were randomly divided into the sham-operated group, the model group, the nimodipine group, and high, medium and low-dose Guhong injection groups, with 10 rats in each group. The middle cerebral artery embolization (MCAO) model was established to observe neurological deficit symptoms, infarct volume, SOD activity, MDA content, GSH-Px and CAT activity in rats, as well as the contents of t-PA, PAI, TXB2 and 6-keto-PGF1α in serum. The results showed that Guhong injection could obviously promote the recovery of neurological deficit symptoms, narrow the brain infarct volume in rats after surgery, significantlyincrease the activities of SOD, GSH-Px and CAT and decrease the content of MDA. Meanwhile, it also could obviously increase the contents of t-PA and 6-keto-PGF1α and decrease the contents of PAI and TXB2 in serum, indicating that Guhong injection have better antioxidant and antithrombus effects, as well as a significant protective effect against cerebral ischemia reperfusion injury in rats.