Compound Danshen Dripping Pill inhibits hypercholesterolemia/atherosclerosis-induced heart failure in ApoE and LDLR dual deficient mice via multiple mechanisms

Heart failure is the leading cause of death worldwide. Compound Danshen Dripping Pill (CDDP) or CDDP combined with simvastatin has been widely used to treat patients with myocardial infarction and other cardiovascular diseases in China. However, the effect of CDDP on hypercholesterolemia/atherosclerosis-induced heart failure is unknown. We constructed a new model of heart failure induced by hypercholesterolemia/atherosclerosis in apolipoprotein E (ApoE) and LDL receptor (LDLR) dual deficient (ApoE-/-LDLR-/-) mice and investigated the effect of CDDP or CDDP plus a low dose of simvastatin on the heart failure. CDDP or CDDP plus a low dose of simvastatin inhibited heart injury by multiple actions including anti-myocardial dysfunction and anti-fibrosis. Mechanistically, both Wnt and lysine-specific demethylase 4A (KDM4A) pathways were significantly activated in mice with heart injury. Conversely, CDDP or CDDP plus a low dose of simvastatin inhibited Wnt pathway by markedly up-regulating expression of Wnt inhibitors. While the anti-inflammation and anti-oxidative stress by CDDP were achieved by inhibiting KDM4A expression and activity. In addition, CDDP attenuated simvastatin-induced myolysis in skeletal muscle. Taken together, our study suggests that CDDP or CDDP plus a low dose of simvastatin can be an effective therapy to reduce hypercholesterolemia/atherosclerosis-induced heart failure.

Identification of liposoluble constituents in Yushu tablets by UPLC-ESI-IT-TOF/MS / 药学学报

In order to identify the chemical constituents of Yushu tablets comprehensively, we studied the chemical constituents of CHCl3 extract from Yushu tablets by the ultra performance liquid chromatography-electrospray ionization-ion trap-time of flight mass spectrometry (UPLC-ESI-IT-TOF/MS). It showed that there were more than 100 compounds separated, and forty-nine peaks among these were identified on the basis of high resolution mass spectrometry data and literature data reported. Determination of twelve peaks was further confirmed by standard substances. These components assigned to the different plant sources mainly included phenylpropanoids, triterpenoids, quinones and m-trihydroxybenzene compounds. By analyzing the chemical components of CHCl3 extract from compound Chinese medicine Yushu tablets comprehensively, this study provided the foundation for studying chemical components, pharmacodynamic substance and quality control of Yushu tablets.

Identification of metabolites of Radix Paeoniae Alba extract in rat bile, plasma and urine by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry / 药物分析学报

Ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF/MS) was developed to identify the absorbed parent components and metabolites in rat bile, plasma and urine after oral administration of Radix Paeoniae Alba extract (RPAE). A total of 65 compounds were detected in rat bile, plasma and urine samples, including 11 parent compounds and 54 metabolites. The results indicated that glucuronidation, hydroxylation and methylation were the major metabolic pathways of the components of RPAE. Furthermore, the results of this work demonstrated that UPLC-Q-TOF/MS combined with MetaboLynx? software and mass defect filtering (MDF) could provide unique high throughput capabilities for drug metabolism study, with excellent MS mass accuracy and enhanced MSE data acquisition. With the MSE technique, both precursor and fragment mass spectra can be simultaneously acquired by alternating between high and low collision energy during a single chromatographic run.

Identification of hydrolysates and alcoholysates of aconitum alkaloids / 中国中药杂志

<p><b>OBJECTIVE</b>To identify products decomposed in high temperature water and alcohol from diester alkaloids such as aconitum alkaloid, in order to study their transformation regularity.</p><p><b>METHOD</b>Structures of multiple converted products were determined by analyzing on multistage mass spectrometry of known compounds and literature searching.</p><p><b>RESULT</b>Benzaconine and pyraconitine were the major hydrolysates, while pyraconitine and ethoxy-aconitine were the major alcoholysates from diester alkaloids.</p><p><b>CONCLUSION</b>Pyraconitine alkaloids, as pyrolytic products, are not related to the type of solvent. 8-ethoxy-aconitine alkaloids, as alcoholysates, are related to the type of solvent. This study identifies multiple converted products from alkaloids and summarizes mass spectrometry fragmentation regularity by LC-MS, laying a firm foundation for studies on the transformation of toxic diester alkaloids contained in aconitum and providing a basis for studies on the transformation of alkaloids contained in aconitum during boiling.</p>

Gastroprotective Effects of Ascaridole on Gastric Ulcer in Rats / 中草药·英文版

ObjectiveTo evaluate the gastroprotective activity of ascaridole.MethodsThe gastroprotective effect of ascaridole was evaluated on ulcer healing in rats with acetic acid-induced chronic gastric ulcer,pylorus ligation- and Aspirininduced gastric ulcer.Ascaridole was ig administered with the dosages of 10 and 20 mg/kg once daily for 7 d.Results Ascaridole showed the significant anti-ulcer effects.In acetic acid-induced gastric ulcer rats,the ulcer areas after 10 and 20 mg/kg of ascaridole treatment were (65.1 ± 20.0) and (50.6 ± 11.0) mm2,respectively,which were significant lower (P ＜ 0.01) than that of the control group [(116.7 ± 35.8) mm2].For pylorus ligation model,ascaridole showed a gastric ulcer healing effect in a dose-dependent manner.Ascaridole at the dose of 20 mg/kg showed 50％ ulcer protection and had a significant (P ＜ 0.05) gastroprotective activity since it decreased the total acidity and pepsin activity.Compared to the control group,the two dosages of ascaridole showed the significant reduction (P ＜ 0.05) in the ulcer index on Aspirin-induced ulcer.ConclusionThis study provides evidence that ascaridole shows potential efficacy on the healing of gastric ulcers induced by acetic acid,Aspirin,and pylorus ligation.

Simultaneous Determination of Silybin A and Silybin B in Rat Plasma and Pharmacokinetic Study / 中草药·英文版

Objective To investigate the bioavailability and pharmacokinetics of silybin A and silybin B in rats,respectively.Methods Following iv and ig administration of silybin to 20 Wistar rats,the plasma samples were collected at different time points up to 12 h.Sample pretreatment was involved in one-step protein precipitation with acetonitrile.Silybin A and silybin B were simultaneously determined by LC-MS/MS.Results After ig dosing silybin 28,56,and 112 mg/kg to rats,the t1/2β values were 5.48,5.08,and 5.73 h for silybin A,and 4.56,4.12,and 5.53 h for silybin B; The Cmax were 674.3,1349.4,and 2042.5 ng/mL for silybin A,and 671.0,1365.4,and 2066.2 ng/mL for silybin B; The Tmax were 0.20,0.23,and 0.20 h for silybin A,and 0.20,0.23,and 0.20 h for silybin B; The AUC were 454.4,845.9,and 1219.5 h·ng/mL for silybin A,and 432.0,817.1,and 1153.6 h·ng/mL for silybin B.The absolute bioavailabilities of silybin A and silybin B were 2.86％ and 1.93％,respectively.Conclusion Silybin A and silybin B have very low bioavailability after ig administration,and there is no significant difference in the pharmacokinetic parameters between silybin A and silybin B,which indicates that the two diastereoisomers have similar pharmacokinetic behavior in rats.

Study on pharmacokinetics of silibinin capsule in Chinese healthy volunteers / 中国药理学通报

Aim To investigate the pharmacokinetic characteristics of silibinin in Chinese healthy volunteers.Methods Nine Chinese male healthy volunteers were divided into receiving orally a single dose of silibinin capsule corresponded 70,140 and 280 mg of silibinin,respectively,in Latin square design study.After administration of silibinin capsule,the plasma concentrations were determined by HPLC with UV detection.The pharmacokinetic parameters were analyzed by Topfit 2.0 program.Results The linearity of this method was found to be from 3.125 to 10 000 μg·L~(-1) with a lower limit of quantitation(LLOQ) of 3.125 μg·L~(-1) for silibinin.The pharmacokinetic parameters were calculated as the follows:at the three different dosages(70,140 and 280 mg),T_(1/2) was 2.44,2.38 and 2.47 h;C_(max) was 1135.6,2841.1 and 3946.9 μg·L~(-1);T_(max) was 1.35,1.26 and 1.39 h;AUC_(0-11 h) was 1287.2,3337.8 and 5398.5 μg·h·L~(-1);AUC_(0-∞)was 1300.7,3377.1 and 5453.9 μg·h·L~(-1);CL/F was 1062.1,824.7 and 943.2 ml·min~(-1);And V_d was 219.9,167.1 and 212.0 L,respectively.Conclusions The developed method is shown to be sensitive,accurate and simple,and can satisfy the requirement of pharmacokinetic study of silibinin in human.The C_(max),AUC_(0-11 h) and AUC_(0-∞) of silibinin in Chinese healthy volunteers(in ranges of 40～120 mg)are fitted with non-linear kinetic model,while there are no significant differences in T_(1/2) at the three different dosages.

The Clinical Research on Treatment of Diabetic Foot with Traditional Chinese Medicine / 国际中医中药杂志

Diabetic Foot is one of common chronic complications of diabetes.The incidence of this disease showed the tendency of increasing.Traditional Chinese medince has obvious preponderance and and good therapeutic effects in treating diabetic foot.The cfinical progress of the traditional Chinese medicine in the treatment of Diabetic Foot in the recent 10 years has been summarized by the article.

Effects of Luotong on the Morphological Changes of Retinal Microvessels in the Streptozotocin-induced Diabetic Rats / 中国中医药信息杂志

Objective To study the protective and therapeutic effect of Luotong on the retinal microvessel kinetic morphological changes during various stages of streptozotocin-induced diabetic rats. Methods The diabetic rat model was setup by a single intraperitoneal injection 65 mg/kg of streptozotocin. Diabetic model rats were randomly divided into diabetic model group (6, 9, 12 months subgroups), diabetic group protected with Luotong (6 months) from the onset of diabetic model (LT group)and diabetic group treated with Luotong (3, 6 months subgroups ) 6 months after the onset of diabetic model (LT1, 2 group). The eyeballs were removed at 6, 9 and 12 months, respectively. The whole mounts of retinal digestion were prepared and stained with PAS staining method. The light microscope and transmission electron microscope morphological observations were performed and the basilar membrane thickness of retinal capillaries were quantitatively analysed by LEICA-Q550IW computer image system. Results At 6 months, the retinal microvessel morphological changes of LT group were less severe than those of 6 month model group. At 9 months of the diabetic model rat, the retinal microvessel morphological changes were prominent. 3 months after Luotong therapy, the retinal microvessel changes were partly improved in comparison with 9 month model group but still aggravated gradually. At 12 months, the retinal microvessel morphological changes of diabetic model rats were very severe. 6 months after Luotong therapy, the retinal microvessel changes were significant mitigated compared with 12 month model group. The results of computer image analysis indicated the retinal capillary basilar membrane thickness in diabetic group protected or treated with Luotong were significant decreased in comparison with homeochronous model group (P

Effects of Rutosids on Apoptosis of Retinal Capillary in Rats with Different Courses of Diabetes / 中华中医药杂志

Objective: To research the effects of Rutosids on apoptosis of retinal capillary in rats with different courses of diabetes.Methods: Diabetes models were prepared by injecting streptozotocin 65mg/kg via rats' abdominal cavity.Diabetes rat models were randomly divided into four groups in terms of diabetes model group(DMG),Rutosids intervention group(RIG),Rutosids therapy group 1(RTG1) and Rutosids therapy group 2(RTG2).Eyeballs were selected separately,retinals digesting stretched preparation capillary samples were prepared,and apoptosis cells were specificity marked by PAS dyeing and ribonucleotide terminal transferase mediating dUTP nick-translation(TUNEL method),to observe below light microscope.Results: Compared with the homeochronous DMG,the apoptosis of retinal pericapillary cells in RIG was not obvious;perithelial cell apoptosis of RTG1 was relatively common,a few endothelial cells were apoptosis;endotheliocyte apoptosis of RTG2 was increased after treating for 3 months,but obviously lighted than 12 months model group.Conclusion: Rutosids has the preferable inhibitory action on perithelial cell apoptosis of early metaphase retinal microangiopathy in diabetes rats.