Effect of Xiongshao Capsule (芎芍胶囊) on Vascular Remodeling in Porcine Coronary Balloon Injury Model

Ｉｔｗａｓｋｎｏｗｎｉｎｇｅｎｅｒａｌｔｈａｔｔｈｅｃｅｎｔｒａｌｋｅｙｏｆｃｏｒｏｎａｒｙｒｅｓｔｅｎｏｓｉｓｆｏｒｍａｔｉｏｎａｆｔｅｒｐｅｒｃｕｔａｎｅｏｕｓｔｒａｎｓ ｌｕｍｉｎａｌｃｏｒｏｎａｒｙａｎｇｉｏｐｌａｓｔｙ（ＰＴＣＡ）ｉｓｔｈｅｉｎｔ     

Effect of Xiongshao Capsule（芎芍胶囊）on the Function of Vascular Endothelium of Patients with Cervical Atherosclerosis

Objective: To study the effect of Xiongshao Capsule (芎芍胶囊, XSC), a TCM herb that can promote blood circulation to remove blood stasis, on the endothelial dependent relaxation function, serum nitric oxide (NO), and plasma endothelin-1 (ET-1) of the patients with cervical atherosclerosis. Methods: Forty patients were randomly divided into two groups: XSC group and Probucol group (western medicine control).In addition, 20 healthy people were set as a normal control group. Plasma ET-1, serum NO, the internal diameter of basal brachial artery, endothelial dependent flow mediated dilation (FMD) and non-endothelial dependent nitroglycerin induced dilation (NID) to the trial group before and after therapy and to the healthy control group were determined respectively. Results: Compared to the healthy control group, FMD of patients with atherosclerosis was damaged obviously, the serum NO level decreased, plasma ET-1 increased (P＜0.01), NID also decreased (P＜0.05), the internal diameter of basal brachial artery has no obvious difference (P＞0.05). After the patients with atherosclerosis were treated with Xiongshao Capsule for 12 weeks,FMD increased evidently, plasma ET-1 decreased, serum NO and the ratio of NO/ET-1 increased, compared with the level before therapy and Probucol group, the difference was significant (P＜0.05, P＜0.01), NIDdidn′t change obviously (P＞0.05). Conclusion: XSC could regulate vascular activity factor and improve the function of endothelial dependent vascular dilation of patients with atherosclerosis.     

Clinical Study of Xiongshao Capsule (芎芍胶囊) in Preventing Restenosis after Coronary Interventional Treatment

Ｓｉｎｃｅｐｅｒｃｕｔａｎｅｏｕｓｔｒａｎｓｌｕｍｉｎａｌｃｏｒｏｎａｒｙａｎｇｉｏｐｌａｓｔｙ（ＰＴＣＡ）ａｎｄ／ｏｒｃｏｒｏｎａｒｙｓｔｅｎｔｉｎｇｃａｎｒｅｃｏｎｓｔｒｕｃｔｃｏｒｏｎａｒｙｂｌｏｏｄｃｉｒｃｕｌａｔｉｏｎｗｉｔｈ ｏｕｔｔｈｏｒａｃ     

Anti-inflammatory Effects of Xuezhikang Capsule (血脂康胶囊)

IthasbeenprovedthatXuezhikangCapsule(XZK,血脂康胶囊),aChinesered yeastriceextract,con tainsmultiplenaturalstatins(8monacolins)andothercomponents,whichcouldsignificantlyreducethetotalcholesterol(TC)andLDL cholesterolconcentrationsinblood.Itsbenefitsoncoro aryheartdiseaseshavebeenstudiedintherecentlyconductedChineseCoronarysecondarypre ventionstudy(CCSPS).TheresultsshowedthatXZKcannotonlysignificantlydecreasetheinci denceofnonfatalmyocardialinfarctionanddeathsfromCHD,butalsosignificantl…     

Effects of Zhizi Chuanxiong Capsule (栀子川芎胶囊) on Abnormal Methylation in Rabbits with Atherosclerosis

Objective: To investigate the effects of Zhizi Chuanxiong Capsule (ZCC, 栀子川芎胶囊) on abnormal DNA methylation in a rabbit model of atherosclerosis (AS). Methods: After 1 week of adaptive feeding, 48 New Zealand white rabbits were randomly divided into 4 groups: a control group (n=12) fed with normal diet for 22 weeks; a model group (n=12) fed with high fat diet for 14 weeks followed by 8 weeks of normal diet feeding; a low-dose ZCC group (n=12) fed with high fat diet and low-dose ZCC for 14 weeks, followed by 8 weeks of normal diet and low-dose drug; a high-dose ZCC group (n=12) fed with high fat diet and high-dose drug for 14 weeks, followed by 8 weeks of normal diet and high-dose drug. After 22 weeks of feeding, blood samples were taken from the rabbit ear vein, and the genomic DNA was extracted for methylation immunoprecipitation sequencing (Medip-seq). The aorta tissues were collected for hematoxylin-eosin (HE) staining. Results: Eight rabbits died during the feeding process. HE staining showed that the size of the lipid deposition on vessel wall and atherosclerotic plaque formation were reduced in both low- and high-dose group. The Medip-seq results showed that there were 146 abnormally methylated genes (including both hypermethylated gene and hypomethylated genes) in the model group, compared with the control group. Gene Ontology (GO) and Pathway analysis showed that these abnormally methylated genes were found to be involved in multiple AS-related functions and pathways, such as protein kinase C activity, cholesterol transport, mitogen-activated protein kinase (MAPK) signaling pathway, peroxisome proliferater-activated receptor signaling pathway, vascular smooth muscle contraction, inflammation and so on. The abnormal methylated genes in AS model group were altered in both low- and high-dose groups: low-dose ZCC could change 72 of the 146 abnormally methylated genes, high-dose ZCC could change 71. Through GO and Pathway analysis, these altered methylated genes were involved in protein kinase C activity, inflammatory pathway, MAPK signaling pathway, vascular endothelial growth factor signaling pathway, etc. Conclusion: ZCC could treat AS through regulating the abnormal hypermethylated and hypomethylated genes in AS rabbit model.     

Effects of Zhizi Chuanxiong Capsule (栀子川芎胶囊) on Abnormal Methylation in Rabbits with Atherosclerosis

Objective: To investigate the effects of Zhizi Chuanxiong Capsule(ZCC, 栀子川芎胶囊) on abnormal DNA methylation in a rabbit model of atherosclerosis(AS). Methods: After 1 week of adaptive feeding, 48 New Zealand white rabbits were randomly divided into 4 groups: a control group(n=12) fed with normal diet for 22 weeks; a model group(n=12) fed with high fat diet for 14 weeks followed by 8 weeks of normal diet feeding; a low-dose ZCC group(n=12) fed with high fat diet and low-dose ZCC for 14 weeks, followed by 8 weeks of normal diet and low-dose drug; a high-dose ZCC group(n=12) fed with high fat diet and high-dose drug for 14 weeks, followed by 8 weeks of normal diet and high-dose drug. After 22 weeks of feeding, blood samples were taken from the rabbit ear vein, and the genomic DNA was extracted for methylation immunoprecipitation sequencing(Medip-seq). The aorta tissues were collected for hematoxylin-eosin(HE) staining. Results: Eight rabbits died during the feeding process. HE staining showed that the size of the lipid deposition on vessel wall and atherosclerotic plaque formation were reduced in both low-and high-dose group. The Medip-seq results showed that there were 146 abnormally methylated genes(including both hypermethylated gene and hypomethylated genes) in the model group, compared with the control group. Gene Ontology(GO) and Pathway analysis showed that these abnormally methylated genes were found to be involved in multiple AS-related functions and pathways, such as protein kinase C activity, cholesterol transport, mitogen-activated protein kinase(MAPK) signaling pathway, peroxisome proliferater-activated receptor signaling pathway, vascular smooth muscle contraction, inflammation and so on. The abnormal methylated genes in AS model group were altered in both low-and high-dose groups: low-dose ZCC could change 72 of the 146 abnormally methylated genes, highdose ZCC could change 71. Through GO and Pathway analysis, these altered methylated genes were involved in protein kinase C activity, inflammatory pathway, MAPK signaling pathway, vascular endothelial growth factor signaling pathway, etc. Conclusion: ZCC could treat AS through regulating the abnormal hypermethylated and hypomethylated genes in AS rabbit model.     

Effects of Quyu Xiaoban Capsule(祛瘀消斑胶囊) on Vascular Endothelial Function in Patients with Atherosclerosis

Objective: To evaluate the therapeutic effects of Quyu Xiaoban Capsule (祛瘀消斑胶囊 ,QYXBC) on endothelial dependent vascular relaxation (EDVR) function in patients with atherosclerosis (AS)with ultrasonic technique. Methods: Tested were the endothelial function and blood lipids of 42 patients with AS in the treated group and 30 healthy volunteers in the control group. And re-examination of these parameters was carried out on the AS patients after they had been treated with QYXBC for 10 months. Results: Before treatment, the reactive hyperemia induced changes in artery diameter in the treated group was significantly lower than that in the control group (P＜0.01), while insignificant difference was found between the two groups in response to nitroglycerin. In the treated group after treatment, with D%-R improved significantly (P＜0.01), total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C)decreased by 16.3%, 5.6%, 10.2% respectively and high-density lipoprotein cholesterol (HDL-C) increased by 7.5%. EDVR was correlated negatively with the serum TC, LDL-C concentrations and the baseline brachial diameter (D0) (r = -0.41, -0.66, -0.59, respectively, all P＜0.01), but correlated positively with HDL-C (r = 0.62, P＜0.05). The ameliorative extent of EDVR was correlated positively to the decreased magnitude of TC and LDL-C concentrations ( r = 0.67,0.59, both P＜0.01 ). Conclusion: QYXBC can lower the level of blood lipids and improve significantly EDVR function.     

Effects of Tongguan Capsule(通冠胶囊)on Post-myocardial Infarction Ventricular Remodeling and Cardiac Function in Rats

<正>Objective:To observe the effects of Tongguan Capsule(通冠胶囊,TGC) on post-myocardial infarction ventricular remodeling and heart function in rats.Methods:A rat model of acute myocardial infarction (AMI) was established by coronary ligation.Experimental rats were randomized to 4 groups including three model groups(Group A:captopril 5 mg/kg·day,n=7;Group B:TGC 10 g/kg·day,n=7;and Group C:placebo, n=8),and a sham-control group(Group D:blank control,n=6).Animals were treated for 4 weeks.The cardiac function of rats was assessed at the end of the experiment based on left ventricular ejection fraction(LVEF) and left ventricular short axis fractional shortening(LVFS) detected by colored echocardiography;meanwhile, the condition of ventricular remodeling was observed through the levels of left ventricular mass(LVM),plasma aldosterone(ALD),myocardial angiotensinⅡ(AngⅡ) and myocardial collagen measurements.Results:At the end of the experiment,LVEF and LVFS in Group A and B were improved significantly,while those in Group C were unchanged,the LVEF in Group A,B,C,and D was 0.57±0.46,0.61±0.08,0.36±0.55 and 0.76±0.02,respectively;and their LVFS was 0.31±0.52,0.34±0.04,0.23±0.57 and 0.45±0.03,respectively.The difference was statistically significant when comparing the two indexes in Group A and B with those in Group C and D(P0.05).LVM,levels of plasma ALD and myocardial AngⅡwere lower in Group A and B than in Group C,but a comparison between Group A and B showed an insignificant difference in lowering LVM and ALD,while the lowering of AngⅡwas more significant in Group B than in Group A(754.7±18.7 pg/mL vs 952.6±17.6 pg/ mL,P0.05).Morphological examination showed that in Group A and B the swollen myocardial cells had shrunk, with regularly arranged myocardial fibers and decreased collagen proliferation,but the improvements in Group B were more significant.Conclusion:TGC could markedly improve the post-infarction ventricular remodeling and cardiac function in rats,showing that the efficacy was better than or equal to that of captopril.     

Xiongshao Capsule (芎芍胶囊) promotes angiogenesis of HUVEC via enhancing cell proliferation and up-regulating the expression of bFGF and VEGF

Objective  

To evaluate the angiogenic effect of the Xiongshao capsule (芎芍胶囊, XSC) in human umbilical vein endothelial cells (HUVEC), and to investigate the possible molecular mechanisms mediating its biological effect.     

Effects of Simvastatin on NF-kB-DNA Binding Activity and Monocyte Chemoattractant Protein-1 Expression in a Rabbit Model of Atherosclerosis

To observe the effects of simvastatin on nuclear factor kappaB （NF-kB）-DNA binding activity and on the expression of monocyte chemoattractant protein-1 （MCP-1） in atherosclerotic plaque in rabbits and to explore the anti-atherosclerotic properties beyond its lipid-lowering effects. Thirty-six New Zealand male rabbits were randomly divided into low-cholesterol group （LC）, high- cholesterol group （HC）, high-cholesterol＋ simvastatin group （HC＋S） and then were fed for 12 weeks. At the end of the experiment, standard enzymatic assays, electrophoretic mobility shift as- say （EMSA）, immunohistochemical staining, and morphometry were performed to observe serum lipids, NF-kB-DNA binding activity, MCP-1 protein expression, intirna thickness and plaque area of aorta respectively in all three groups. Our results showed that the serum lipids, NF-kB-DNA binding activity, expression of MCP-1 protein, intima thickness, and plaque area of aorta in the LC and HC＋S groups were significantly lower than those in the HC group （P〈0.05）. There was no significant difference in the serum lipids between the LC and HC＋S groups （P〉0.05）, but the NF-kB-DNA binding activity, the expression of MCP-1 protein and the intirna thickness and plaque area of aorta in the HC＋S group were significantly decreased as compared to the LC group （P〈0. 05）. This study demonstrated that simvastatin could decrease atherosclerosis by inhibiting the NF-kB-DNA binding activity and by reducing the expression of MCP-1 protein.     

A multi-center randomized double-blind placebo-controlled trial of Xiongshao Capsule (芎芍胶囊) in preventing restenosis after percutaneous coronary intervention: A subgroup analysis of senile patients

Objective  

To evaluate the safety and efficacy of Xiongshao Capsule (芎芍胶囊, XS), consisting of Chuangxiongol and paeoniflorin, in preventing restenosis after percutaneous coronary intervention (PCI) in senile coronary heart disease (CHD) patients.     

Effects of Simvastatin on NF-κB-DNA Binding Activity and Monocyte Chemoattractant Protein-1 Expression in a Rabbit Model of Atherosclerosis

Previous studies have demonstrated that ex-peri mental hypercholesterolemialeads to the ather-oma formation and thus lipid lowering could de-crease the development of atherosclerosis . Recentevidence showed that inflammatory responsesmight play an i mportant role in the process ofatherogenesis[1]. Therefore , anti-inflammatorytherapy has become an i mportant therapeuticmeans for the prevention of atherosclerosis .In re-cent years , 3-hydroxy-3-methylglutaryl coenzymeA ( HMG-CoA) reductase in…     

Intervention of Tongxinluo Capsule (通心络胶囊) against Vascular Lesion of Atherosclerosis and Its Effect on Lectin-like Oxidized Low Density Lipoprotein Receptor-1 Expression in Rabbits

Lectin-like oxidized low-density lipoprotein(ox-LDL) receptor-1 (LOX-1) is a newly identifiedreceptor for cytotoxic ox-LDL in endothelial cellsand plays an i mportant role in the occurrence anddevelopment of atherosclerosis ( AS)(1). Clinicalstudies have showed that Tongxinluo capsule (通心络胶囊,TXL) could alleviate the symptoms of angi-na and myocardial ischemia in patients with coro-nary heart disease.But there werefewstudies con-cerning the effect or therapeutic mechanism of itspreve…     

Effects of Corocalm (Shuguan Capsule, 疏冠胶囊) on acute myocardial ischemia in anesthetized dogs

Objective:To investigate the effects of Corocalm (Shuguan Capsule,疏冠胶囊) on acute myocardial ischemia in anesthetized dogs and its possible therapeutic mechanism.Methods:The acute ischemia model was established by ligating the left anterior descending (LAD) artery.Twenty- five dogs were randomly divided into 5 groups (5 clogs in each group):the control group (treated with normal saline 3 mL/kg),the refined Guanxin Capsule group (精制冠心胶囊,GXC 200 mg/kg),high and low dose Corocalm groups (48.5 mg/kg for low dose group and 194.0 mg/kg for high dose group) and the Diltiazem group (5 mg/kg).The animals were treated via a single duodenal administration after the model was established.The experiments used epicardial electrocardiogram (EECG) to measure the scope and degree of myocardial ischemia.Simultaneously,the coronary blood flow (CBF) and serum activity levels of creatine phosphokinase (CK) and lactate dehydrogenase (LDH) were measured by electromagnetic flow meter and automatic biochemical analyzer respectively.The plasma endothelin (ET) content was quantified by radioimmunoassay.Results:Corocalm (48.5 mg/kg and 194.0 mg/kg) significantly decreased the degree and scope of myocardial ischemia,reduced the infarct area,markedly increased the CBF,and inhibited the increase of CK and LDH activities and ET levels induced by myocardial ischemia/infarction.Conclusion:Corocalm could improve the state of acute myocardial ischemia and infarction in dogs.The mechanism of action might be correlated to increasing CBF, inhibiting CK and LDH activities and preventing ET release.     

Clinical Study on Protective Effect of Xinmaitong Capsule(心脉通胶囊) on Damage of Vascular Endothelial Cells

Ｅｎｄｏｔｈｅｌｉｎ（ＥＴ）ａｎｄｃａｌｃｉｔｏｎｉｎｇｅｎｅｒｅｌａｔｅｄｐｅｐｔｉｄｅ（ＣＧＲＰ）ａｒｅａｐａｉｒｏｆｎｅｗｌｙｆｏｕｎｄｖａｓｃｕｌａｒａｃｔｉｖａｔｉｎｇｍｅｄｉａｗｉｔｈｏｐｐｏｓｉｔｉｖｅａｃｔｉｏｎ．ＥＴｉｓａｖａｓｏｃｏｎｓｔｒｉｃｔｉｖｅｐｅｐｔｉｄｅｐｒｏｄｕｃｅｄｂｙｖａｓｃｕｌａｒｅｎｄｏｔｈｅｌｉａｌｃｅｌｌｓ（ＶＥＣ）ｗｉｔｈｓｔｒｏｎｇａｎｄｐｒｏｔｒａｃｔｅｄｅｆｆｅｃｔ,ｔｈｅｓｔｒｏｎｇｅｓｔｖａｓｏｃｏｎｓｔｒｉｃｔｏｒｉｎｔｈｅｈｕｍａｎｂ…     

Effects of Oxidized Low Density Lipoprotein on the Expression and Function of ABCA1 in Macrophages

In the present study, we examined the regulation of the expression and function of ABCA1 by modified LDL (ox-LDL) in vitro. After incubation with apoA-I for 24 h, RAW264.7 cells effluxed 37.65 % cholesterol loaded by acetyl LDL (ac-LDL), and 9.78% cholesterol in ox-LDL group. The level of ABCA1 mRNA increased about three times either when cells were incubated with .100 μg/mL ac-LDL or with 100 μg/mL ox-LDL. However, the level of ABCA1 protein rose by 1.57 times in ac-LDL group and 1.26 times in ox-LDL group. These results demonstrated that ox-LDL had different effect on the expression and function of ABCA1, ox-LDL might decrease the cholesterol efflux mediated by ABCA1 through other unknown mechanisms.     

Effects of Tangshenkang Capsule(糖肾康胶囊) on Disbetic Nephropathy

ＥｆｆｅｃｔｓｏｆＴａｎｇｓｈｅｎｋａｎｇＣａｐｓｕｌｅｏｎＤｉｓｂｅｔｉｃＮｅｐｈｒｏｐａｔｈｙ￥ＷＡＮＧＸｉａｎ－ｂｏ；ＳＡＮＧＹａｎ；ＨＡＮＱｉｎｇＧＵＯＢａｏ－ｒｕｉａｎｄＬＩＵＸｉ－ｘｉｎ（ＴｈｅＦｉｒｓｔＡｆｆｉｌｉａｔｅｄＨｏｓｐｉｔａ...     

Effects of Jinmaitong Capsule (筋脉通胶囊) on Ciliary Neurotrophic Factor in Sciatic Nerves of Diabetes Mellitus Rats

Objective:To study the effects of the Chinese medicine Jinmaitong Capsule(筋脉通胶囊,JMT) on the pathomorphology of sciatic nerves,ciliary neurotrophic factor(CNTF),and the mRNA expressions of CNTF in rats with streptozotocin-induced diabetes mellitus(STZ-DM).Methods:The animal model was established by one time intraperitoneal injection of streptozotocin.The rats were simply divided by random into 5 groups including model group,low-dose JMT group(JL),medium-dose JMT group(JM),high-dose JMT group(JH) and neurotropin group.For each of the above 5 groups,a group of 10 normal Wistar rats matched in body weight,age and gender were set as normal group.Intragastric administrations were started after the animal model established.The JL group were administered with five times the JMT dose recommended for a human adult;the JM group were administered with ten times the JMT dose recommended for a human adult;the JH group were administered with twenty times the JMT dose recommended for a human adult.The neurotropin group was administered with ten times the neurotropin dose recommended for a human adult.All rats were given intragastric administration for 16 weeks and then killed.In the 4th,8th,12th,16th week,body weight and blood glucose level were detected before and after the intervention.The morphologic changes of the sciatic nerves were observed by optical microscope and transmission electron microscope.The CNTFmRNA expressions were detected by real-time fluorescent quantitative polymerase chain protein,and the CNTF protein expressions were detected by immunohistochemical method.Results:The blood glucose levels of the STZ-DM rats were much higher than normal group(P<0.01),and there was no apparent difference between any treatment groups and the model group(P>0.05).Before and after the intervention in the 4th, 8th,12th,16th week,there were no significant differences in the body weight among all the groups(P>0.05). The sciatic nerves of STZ-DM rats might have pathomorphological changes in axons,myelin sheaths,and interstitium.The levels of CNTF and CNTF-mRNA expressions in the STZ-DM rats were both significantly decreased(P<0.01).The sciatic nerves of STZ-DM rats might have pathomorphological changes in axons, myelin sheaths,and interstitium.Conclusion:JMT could improve the pathomorphology of sciatic nerves by increasing CNTF’s and CNTF-mRNA expressions in sciatic nerve tissues,and promote the repair and regeneration of damaged nerve fibers.     

Inhibitory Effects of Qushuanling Capsule (祛栓灵胶囊) on Thrombus Formation and Platelet Aggregation in Rats

Objective:To investigate the effects of Qushuanling Capsule（祛栓灵胶囊,QSLC） on thrombus formation and platelet aggregation in rats.Methods:Arteriovenous bypass,venous thrombosis,and middle cerebral artery thrombosis models were used in rats to investigate the anti-thrombotic effects of QSLC,a compound of nine Chinese herbs.The platelet aggregation induced by adenosine diphosphate（ADP）,thrombin or arachidonic acid（AA）,as well as the contents of thromboxane B₂（TXB₂） and 6-keto-prostaglandin F1α（6-keto-PGF1α） in rat plasma and aortic walls,were determined to investigate the possible mechanisms of the anti-thrombotic effects of QSLC.Results:After oral administration with QSLC for 7 days,arteriovenous bypass thrombosis was obviously suppressed compared with the model group,venous thrombosis was also obviously suppressed,rat behaviors were obviously improved,and brain infarct size as well as water content were also reduced.The platelet aggregation induced by ADP or thrombin was inhibited by QSLC,but the drug had no effect on AA-induced platelet aggregation and content of TXB₂ and 6-keto-PGF1αin plasma and the aortic wall.Conclusion:These results suggest that QSLC can be used in the prevention and treatment of thrombotic diseases,and that its mechanism of action may be related to inhibition of platelet aggregation.