Effects of Xuesetong Soft Capsules(血塞通软胶囊) on angiogenesis and VEGF mRNA expression in ischemic myocardium in rats with myocardial infarction

OBJECTIVE:To observe the effects of Xuesetong Soft Capsules(血塞通软胶囊,Notoginseng total saponin) on angiogenesis and vascular endothelial growth factor(VEGF) mRNA expression in ischemic myocardium of rats with myocardial infarction.METHODS:The left coronary artery of rats was ligated to establish the animal model of acute myocardial infarction.Rats were randomly divided into Xuesetong Soft Capsule,Shexiangbaoxin Pill(positive control),model(negative control) and sham operation groups.After 6 weeks,microvessel count(MVC),microvessel density(MVD) and VEGF mRNA expressioninischemicmyoc ardium were evaluated.RESULTS:MVC and MVD in the myocardial infarct border area in model,Shexiangbaoxin Pill and Xuesetong Soft Capsule groups significantly increased compared with those of the sham operation group(P<0.05).MVC and MVD in the myocardial infarct border area in Xuesetong Soft Capsule and Shexiangbaoxin Pill groups significantly increased compared with those of the model group(P<0.05).No significant differences between Xuesetong Soft Capsule and Shexiangbaoxin Pill groups were observed(P>0.05).The model group showed signifi-cantly higher VEGF mRNA expression than that in the sham operation group(P<0.05).Xuesetong Soft Capsule and Shexiangbaoxin Pill groups showed significantly higher VEGF mRNA expression than that of the model group(P<0.05).No significant difference between Xuesetong Soft Capsule and the Shexiangbaoxin Pill groups was observed(P>0.05).CONCLUSION:Xuesetong Soft Capsules promote angiogenesis in ischemic myocardium after myocardial infarction and the mechanism may be associated withVEGF mRNA expression.

Effect of Xuesaitong Soft Capsule (血塞通软胶囊) on Hemorrheology and in Auxiliarily Treating Patients with Acute Cerebral Infarction

Objective: To observe the therapeutic effect of Xuesaitong soft capsule(血塞通软胶囊, XST)and its effect on platelet counts, coagulation factor 1 (CF1) as well as hemorrheologic indexes in treating patients with acute cerebral infarction (ACI). Methods: Two hundred and four patients with ACI were assigned into two groups, the control group (n=96) and the treated group (n=108). They were all treated with conventional Western medicines, including mannitol, troxerutin, citicoline, piracetam and aspirin, while to the treated group, XST was given additionally through oral intake, twice a day, 2 capsules each time for 8 successive weeks. The clinical efficacy was evaluated according to the nerve function deficits scoring and the changes of platelet count. CF1 and hemorrheological indexes were measured before and after treatment.Results: The total effective rate was 87.0% in the treated group, and 87.5% in the control group, respectively, showing insignificant difference between them. But the markedly effective rate in the treated group ( 66.7%) was significantly higher than that in the control group (27.1%, P<0.01). The count of platelet was not changed significantly in both groups after treatment, while CF1 in them evidently lowered at the end of the 4th and 8th weeks of treatment, but showed insignificant difference between the two groups. The hematocrit, whole blood viscosity and plasma viscosity in both groups were all improved significantly after treatment, but also showed insignificant difference in comparison of the two groups. Conclusion: XST has good efficacy in auxiliary treatment of patients with ACI, though its mechanism remains to be further explored.

Effects of Hemp seed soft capsule on colonic ion transport in rats

AIM To investigate the effect of Hemp seed soft capsule(HSCC) on colonic ion transport and its related mechanisms in constipation rats.METHODS Sprague-Dawley male rats were randomly divided into three groups: normal group, constipation group and HSSC group. Rats in the constipation and HSSC groups were administrated loperamide 3 mg/kg per day orally for 12 d to induce the constipation model. Then, the HSSC group was given HSSC 0.126 g/kg per day by gavage for 7 d. The normal and constipation groups were treated with distilled water. After the treatment, the fecal wet weight and water content were measured. The basal short-circuit current(Isc) and resistance were measured by an Ussing Chamber. Besides the in vivo drug delivery experiment above, an in vitro drug application experiment was also conducted. The accumulative concentrations of HSSC(0.1 mg/m L, 0.5 mg/m L, 1.0 mg/m L, 2.5 mg/m L, 5.0 mg/m L, 10.0 mg/m L and 25.0 mg/m L) were added to the normal isolatedcolonic mucosa and the Isc was recorded. Further, after the application of either ion(Cl^-or HCO_3^-) substitution, ion channel-related inhibitor(N-phenylanthranilic acid, glybenclamide, 4,4-diisothiocyano-2,2-stilbenedisulfonic acid or bumetanide) or neural pathway inhibitor [tetrodotoxin(TTX), atropine, or hexamethonium], the Isc induced by HSSC was also measured. RESULTS In the constipation group, the fecal wet weight and the water content were decreased in comparison with the normal group(P < 0.01). After the treatment with HSSC, the fecal wet weight and the water content in the HSSC group were increased, compared with the constipation group(P < 0.01). In the constipation group, the basal Isc was decreased and resistance was increased, in comparison with the normal group(P < 0.01). After the treatment with HSSC, the basal Isc was increased(P < 0.05) and resistance was decreased(P < 0.01) in the HSSC group compared with the constipation group. In the in vitro experiment, beginning with the concentration of 1.0 mg/m L, differences in Isc were found between the experimental mucosa(with HSSC added) and control mucosa. The Isc of experimental mucosa was higher than that of control mucosa under the same concentration(1.0 mg/m L, P < 0.05; 2.5-25 mg/m L, P < 0.01). After the Cl^-or HCO_3^-removal and pretreated with different inhibitors(c AMPdependent and Ca^(2+)-dependent Cl^-channels, Na^+-K^+-2 Cl^-cotransporter(NKCC), Na^+-HCO_3^-cotransporter or Cl^-/HCO_3^-exchanger inhibitor), there were differences between experimental mucosa and control mucosa; the Isc of experimental mucosa was lower than that of control mucosa under the same concentration(P < 0.05). Meanwhile, after pretreatment with neural pathway inhibitor(TTX, atropine, or hexamethonium), there were no differences between experimental mucosa and control mucosa under the same concentration(P > 0.05).CONCLUSION HSSC ameliorates constipation by increasing colonic secretion, which is mediated via the coaction of c AMPdependent and Ca^(2+)-dependent Cl^-channels, NKCC, Na^+-HCO_3^-cotransporter or Cl^-/HCO_3^-exchanger.

Clinical Observation of the Effect of Xuesaitong Soft Capsule (血塞通软胶囊) on Post-hepatitis Fibrosis

Objective: To study the effect of Xuesaitong soft capsule (血塞通软胶囊, XST) on liver fibrosis criteria in patients with post-hepatitis fibrosis. Methods: Sixty-four patients with such fibrosis were randomly divided into the treated group and control group. They were treated with XST and Dahuang Zhechong pill (大黄NFDA1虫丸) for 3 months respectively. Their liver fibrosis criteria were examined before and after treatment. Results: The levels of serum procollagen Ⅲ, hyaluronic acid, collagen Ⅳ, laminin in the two groups were significantly lower ( P <0.01) than those before treatment. The differences between the two groups were insignificant ( P >0.05). Conclusion: XST could recover liver dysfunction and had anti-liver fibrosis function.

Study of Interference Treatment by Xuesaitong (血塞通) Soft Capsuleon Patients of Nephrosis Syndrome with Qi Deficiency and Blood Stasisduring Dose Reducing Stage of Corticosteroid

Objective: To observe the effect of Xuesaitong (血塞通, XST) soft capsule in interference treatment on patients of nephrosis syndrome (NS) during corticosteroid (CS) dose reducing stage. Methods: Seventy-one NS patients applying prednisone and initiating dose reducing stage were randomized into trial group and control group. On the basis of conventional prednisone dose reduction of both groups, the trial group was given additionally XST, and the treatment course ended with the reduction to maintenance dose. In the course of observation, those who did not comply with the criteria of observation were excluded. Before and after the dose reduction, TCM syndrome scoring, 24 hrs urinary protein amount, blood β2-microglobulin (β2-MG), urinary β2-MG, blood fibrinogen (Fbg), plasma prothrombin time (PT), blood lipid, etc. were observed. Results: The trial group of XST could obviously lower their urinary protein amount and blood lipid level (P<0.05 or P<0.01), markedly improve the blood coagulation parameters (P<0.01), improve the TCM syndrome and CS induced adverse reaction (P<0.05 or P<0.01), also obviously reduced the recurrence rate of NS (P<0.05). Conclusion: XST could obviously improve the clinical symptoms and renal impairment parameters in NS patients during CS dose reduction stage, improve the CS induced adverse reaction and prevent the recurrence of NS.

HPLC Study on HPLC Characteristic Spectrum of Huoxiang(Herba Agastachis)Eliminating Summer-heat Soft Capsule

To establish HPLC characteristic spectrum of Huoxiang(Herba Agastachis)Eliminating Summer-heat Soft Capsule.Chromatographic separation was performed on Tech Mate C18-ST(5 um,4.6×250 nm)column by Agilent 1260 high performance liquid chromatograph,eluted with acetonitrile and 0.05%phosphoric acid in a gradient elution at a flow rate of 1.0 mL∙min-1.The detection wavelength was set at 270 nm.Hesperidin was selected as the reference peak to calculate the RSD of the relative retention time.Precision,stability and reproducibility were investigated as well.80 different samples from 5 manufacturers were included in this study.The HPLC characteristic spectrum of Huoxiang Eliminating Summer-heat Soft Capsule was constructed with 11 specific chromatographic peaks in 80 samples.The method is accurate,reliable and with good reproducibility,and could overall control the quality of Huoxiang Eliminating Summerheat Soft Capsule.

Comparison of pharmacokinetics of different oral Panax notoginseng saponins using ultra-high performance liquid mass spectrometry

Objective:To discuss and compare the plasma pharmacokinetics after three oral Panax notoginseng saponin(PNS)administrations in beagle dogs.PNS is the main active ingredient of the traditional Chinese medicine(TCM)Panax notoginseng.Although its outstanding therapeutic efficacy has been demonstrated by various researchers,its broader application is restricted by the low bioavailability of PNS.Methods:An ultra-high performance liquid chromatographyetandem mass spectrometry(UPLC-MS/MS)method for the simultaneous quantification of notoginsenoside R1,ginsenoside Rg1,ginsenoside Rb1,ginsenoside Rd,and ginsenoside Re in beagle dog plasma was developed and validated.The plasma samples were subjected to liquideliquid extraction with acetone and methanol,and separated on an ACQUITY C18 column(100×2.1 mm ID,1.7 mm)using acetonitrile and water as the mobile phase with a run time of 4.5 min.Results:The analytes were detected without interference in Selected Reaction Monitoring mode with positive electrospray ionization.The validated method was successfully used in comparative pharmacokinetic studies of the five saponins in beagle dogs after oral administration of three PNS preparations.Blood samples were collected up to 192 h after administration and pharmacokinetic parameters were calculated using DAS 3.20 and SPSS 17.0.The AUC_(0-t)values of Re and R1 were significantly higher in soft capsules than in hard capsules.However,the AUC_(0-t)values between hard and soft capsules were not significantly different for the other three componentsdRb1,Rd and Rg1.Conclusion:Our intuitive analysis suggests that the bioavailability of PNS in soft capsules is greater than in hard capsules.

SilTech: A New Approach to Treat Aerobic Vaginitis

Background: The aerobic vaginitis (AV) is characterized by increased levels of aerobic bacteria, vaginal inflammation and depressed levels of lactobacilli. Objective: The purpose of this study was to investigate the therapeutic efficacy of SilTechTM vaginal softgel capsules, containing new microcrystals of silver monovalent ions, for aerobic vaginitis (AV). Methods: This prospective study enrolled 32 women diagnosed with AV. All recruited women were treated with SilTechTM vaginal softgel capsules once daily for 7 days (one course). Therapeutic efficacy was evaluated based on clinical and microscopic criteria, and cure rates were calculated. Women who were improved (but not cured) received a second course of therapy. Patients classified with clinical and microscopic failure were treated using other strategies. Results: After one course of therapy, 59.2% (19/32) of women were cured, 19.0% (6/32) were improved (but not cured) and 21.8% (7/32) failed to respond to the therapy. After two courses of therapy, clinical improvement was achieved in additional two women. The therapy was very well tolerated, and during the entire study no drop out related to the SylTechTM vaginal capsules treatment was observed;only two patients (6.2%) experienced a mild transient burning after application. Conclusion: SylTechTM vaginal capsules is an effective therapeutic option for patients with AV, and most women with AV were cured with one course of therapy.

A Multicenter,Randomized,Double-blind Clinical Study on Wufuxinnaoqing Soft Capsule(五福心脑清胶囊) in Treatment of Chronic Stable Angina Patients with Blood Stasis Syndrome

Objective： To confirm the efficacy and safety of Wufuxinnaoqing Soft Capsule （五福心脑清胶囊, WSC） in the treatment of chronic stable angina （blood stasis syndrome）. Methods： A multicenter, randomized, double-blind, placebo-controlled trial with superiority test was designed. A total of 240 patients with chronic stable angina （blood stasis syndrome） from multiple centers were randomly and equally assigned to the treatment group and the control group. Based on standard treatment of Western medicine, the treatment group was given WSC, while the control group was given WSC mimetic, both for 12 weeks. Observed indicators included the efficacy in angina, the efficacy in Chinese medicine syndrome, the withdrawal or reduce rate of nitroglycerin and routine safety indices. Results： After 12-week treatment, the significant effective rate and total effective rate of the treatment group were significantly better than those of the control group （23.5% vs. 9.2%, 64.7% vs. 30.8%）, respectively, with statistically significant difference （P〈0.01）. After 12-week treatment, the decreased points and the decreased rate of angina symptom score in the treatment group were better than in the control group （5.1±4.2 points vs. 2.8± 3.5 points, 44.9% ±37.2% vs. 25.4%±30.7%） respectively, with significant difference （P〈0.01）. After 12-week treatment, the significant effective rate and total effective rate of the treatment group were better than the control group （respectively, 30.3% vs. 15.0%, 67.2% vs. 45.0%, P〈0.01）. After 8- or 12-week treatment, the decreased points and the decreased rate of Chinese medicine syndrome score in the treatment group were better than the control group （P〈0.05 or P〈0.01）. After 12-week treatment, nitroglycerin withdrawal rate and the withdrawal or reduce rate in treatment group were better than the control group （P〈0.01）. On safety evaluation, the incidence of adverse events （7.563% vs. 7.500%） and the incidence of cardiovascular events （0.840% vs. 0.000%） in the treatment group were similar with the control group, and the difference was not statistically significant （P〉0.05）. Couch=SlOB： In treatment of chronic stable angina （blood stasis syndrome）, WSC can reduce angina attacks and consumption of nitroglycerin, decrease angina severity degree, effectively relieve the blood stasis syndromes, such as chest pain, chest tightness, palpitations, dark purple tongue and other symptoms. Besides, adverse events and cardiovascular adverse events in the treatment group and the control group showed no difference. All shows that the drug is safe and effective. [This study was registered in Chinese Clinical Trial Registry （ChiCTR）, with registration number： ChiCTR-TRC-14005158.]