AIM: To study the effect of Rongban Tongmai Granules on hyperlipidemia and atheriosclerosis in rabbits. METHODS: The model of experimental atherosclerosis was prepared by feeding high cholesterol and lipid diet for weeks.After 4 weeks,hyperlipidemic rabbits were randomly divided into five groups,model group,high,medium and low doses of Rongban Tongmai Granules and Shujiangzhi group,taking medicine for 8 weeks.Their blood lipid levels(TC,TG,LDL-C,HDL-C,VLDL-C and TC/HDL-C) were measured before experiment,after treatment,for 4 weeks and for 8 weeks.After having been treated for 8weeks,lipid levels in aortic tissue and liver tissue were estimated,and pathologic changes in aortic and coronary arteries were also observed. RESULTS: The medicine could decrease TC,TG,LDL-C,VLDL-C and TC/HDL-C in serum,TC in liver tissue,and TC,TG in aorta tissue of atherosclerotic rabbits.It could also reduce aortic atherosclerotic plaque coverage of aortic initial surface,initial thickness,foam cells,and the average score representing the degree of coronary arteries stenosis. CONCLUSION: Rongban Tongmai Granules can lower lipid level in serum and related tissue,and prevent the formation of atherosclerosis.

AIM:To explore the dynamic changes of ET,NO,SOD and MDA in atherosclerosis obliterans(ASO) rabbits,as well as the effects of Tongxinluo Capsule(Radix et Rhizoma Ginseng,Hirudo,Scorpio,Eupolyphaga seu Steleophaga,etc.)(TXL) and the candidate mechanisms. METHODS: Rabbits were randomly divided into 7 groups: sham,model,TXL(0.8,0.4,0.2 g/kg),Tongsaimai tablet(0.8 g/kg) and Laishike((0.002 g/kg)).The animal model of ASO was established with a combined method of mechanical trauma,immunologic injury and high fat fodder feeding.Rabbits were administrated the drugs for 8 weeks after surgery.The levels of ET,NO,SOD and MDA were determined at the time points below: pre-experiment,pre-drug administration,4 weeks after drug administration,8 weeks after drug administration,12 weeks after drug administration.The histopathological changes in iliofemoral artery were examined after opacification. RESULTS: TXL significantly extenuated the decrease in the caliber of the iliofemoral artery of the injured hind limb and decreased MDA content while increased SOD activity and NO content in serum. CONCLUSION: TXL might show effects on improving endothelial cell dysfunction,clearing free radicals and antagonizing lipid peroxidation,which might be the candidate mechanisms for the prevention and treatment of TXL for ASO.

Tong-Mai(TM) granules were composed ofRadix Salviae Miltiorrhizae(Danshen),Rhizoma Chuanxiong(Chuanxiong) andRadix Puerariae(Gegen). It had the effect of activating blood circulation. It had been used to treat ischemic cardio-cerebrovascular diseases in the clinical practice. This research combined serum pharmacochemistry and serum pharmaocology to study the material basis of active components in TM granules. After single or multiple intragastric administrations of TM granules, serum blood samples of rats were collected at different time points. LC-MS/MS method was developed to analyze chemical components of TM in blood serum samples. The cardiomyocyte hypoxia / reoxygenation (H/R) model was used in the evaluation of cardiomyocyte protection by TM. The correlation analysis was also conducted between serum concentration of TM and cardiomyocyte activity. The results showed that 8 components of pueraria flavonoid, 5 components of salvianolic acids and 2 components fromGegen were promptly absorbed and reached their highest concentrations at 5 or 30 min after administration. After 3 times of medication, the serum concentration was obviously higher compared to single medication. The drug-serum of TM showed significant protective effect on the cardiomyocyte H/R injury with dose-effect relationship. Daidzein, lithospermic acid, salvianolic acid A, salvianic acid A and rosmarinic acid presented as the most correlated components linked to the effect of activating blood circulation by TM. The serum pharmacochemistry / serum pharmacology related studies provided references for the verification of material basis of active components in compound Chinese medicine.

The rat model of multi-infarct was adopted in this study to elucidate the protective mechanism of Sailuotong capsule (Sailuotong) in recovery period of multiple cerebral infarction. The effects of Sailuotong on levels of Glu, GABA and the expression of NMDA receptor subtypes including NR1, NR2A and NR2B, were detected. The multi-infarct model rats were established by injecting embolizing microsphere via internal carotid artery, and were given Sailuotong treatment (16.5 and 33.0 mg x kg(-1)) for 60 days. The pathological changes in brain ultrastructure were observed by transmission electron microscope. The levels of Glu and GABA in brain tissue were measured with high performance liquid chromatography. The expression of NMDA receptors including NR1, NR2A and NR2B in neurons was evaluated by immunohistochemical staining. Compared with the sham rats, abnormal changes were observed in ultrastructures of neurons, neuroglia cells and synapses of model rat brains. Moreover, significant decrease of Glu and GABA, as well as the elevated expression of NR1, NR2A and NR2B were detected in brain tissues. Sailuotong (16.5 and 33.0 mg x kg(-1)) could improve ultrastructure of cerebral tissue, facilitate synthesis of Glu and GABA, and down-regulate expression of NR1, NR2A and NR2B in neurons. The results demonstrated that Sailuotong could exert neuroprotective effects to some extent in the recovery phase of multiple cerebral infarction by promoting expression of NMDA receptors and synthesis of Glu and GABA.

Sai-Luo-Tong (SLT) is a compound preparation composed of ginseng, ginkgo and saffron for the treatment of vascular dementia. In order to identify its material foundation and provide evidence for therapeutic regimen, the plasma concentration, pharmacokinetics and brain distribution of ginkgolides were investigated after intragastric ad-ministration of SLT. An LC-MS/MS method was developed for the determination of 4 ginkgolides in rat plasma and brain simultaneously. Statistical analysis of obtained data demonstrated that the method had achieved the desired lin-earity, precision, accuracy and sensitivity. The results showed that after administration of SLT at the dose of 60 mg·kg-1, 4 ginkgolides were all absorbed into systemic circulation with AUC value in the order of bilobalide B (BB) >ginkgolide A (GA) > ginkgolide B (GB) > ginkgolide C (GC). All ginkgolides exhibited short half lives less than 2.8 h among which BB showed the shortest t1/2 of 1.61 h. The determination of brain distribution at different time after dos-ing revealed ginkgolides entered into brain promptly dominated by GA and BB. The concentrations of 4 ginkgolides in brain were much lower than these in plasma and declined along with time rapidly. It was concluded that ginkgolides can be absorbed in blood and penetrated into brain rapidly. GA, BB and GB might be main components which effect both periphery and brain collectively by means of their specific mechanism to achieve the therapeutic efficacy on vascular dementia of SLT.

An improved everted gut sac method was applied to the study of prescription compatibility effect on the major components in Danshen extracts. With the separation and detection by HPLC-ECD, 5 major peaks could be detected in intestinal absorbed solution after prescription administration. Following the identification by HPLC-MS/MS, peak 2, 3, 4, and 5 were rosmaric acid, lithospermic acid, salvianolic acid B, and salvianolic acid A, respectively, which also confirmed with reference standards of those components. Through paralleling substance identification, peak 2, 3, 4, and 5 could be found as the major components in Danshen extracts, except Salvianolic acid E which is undetectable in intestinal solution. The contents of peak 2, 3, and 4 did not show difference before and after compatible prescription administrated, where the peak 5 had a significant increase in the same process. Those results revealed that peak 5, salvianolic acid A, might lead to an increasing pharmacological effect after prescription compatibility.

OBJECTIVETo observe the therapeutic effects of Rongban Tongmai granule on oxidative stress in atherosclerotic rabbits.

METHODThe experimental rabbits were randomly divided into control group and hyperlipidemic group. The model of experimental atherosclerosis was prepared by feeding high cholesterol and lipid diet for weeks. After 4 weeks, hyperlipidemic rabbits were randomly divided into five groups, model group, high, medium and low doses of Rongban Tongmai granule and Shujiangzhi group, taking medicine for 8 weeks. The level of NO, ox-LDL, LP(a), SOD and MDA in the serum was measured before experiment, after treatment, treated for 4 weeks and for 8 weeks. After treated for 8 weeks, the level of MDA, GSH and NO, as well as activity of SOD and GSH-Px in the liver of rabbits was determined, meanwhile, the pathologic morphology of aortas was observed by light microscope.

RESULTCompared with control group, aortic intima of rabbits in model group had obviously thickened and developed atherosclerotic plaque. The serum level of MDA and LP(a) in model group had increased (P < 0.01) at 12 weeks after feeding high cholesterol and lipid diet, but the activity of SOD and level of NO were decreased (P < 0.01, P < 0.001). At the same time, the level of MDA in the liver had been elevated (P < 0.01), but the activity of SOD, GSH and NO was decreased (P < 0.01, P < 0.001) in 12 weeks. Rongban Tong-mai granule could inhibit atherosclerotic lesion in aorta, decrease the level of MDA and LP(a) (P < 0.05), increase the activity of SOD and NO (P < 0.05) after treated for 8 weeks in serum, moreover, the activity of SOD, GSH and NO content in the liver were increased (P < 0.05), as well as MDA was decreased (P < 0.05).

CONCLUSIONRongban Tongmai granule can prevent atherosclerosis by antioxidative stress and correcting unbalance of redox.

Animals ; Antioxidants ; administration & dosage ; Atherosclerosis ; blood ; drug therapy ; metabolism ; pathology ; Disease Models, Animal ; Drugs, Chinese Herbal ; administration & dosage ; Glutathione ; blood ; Humans ; Lipoproteins, LDL ; blood ; Malondialdehyde ; blood ; Oxidative Stress ; drug effects ; Plaque, Atherosclerotic ; Rabbits ; Random Allocation ; Superoxide Dismutase ; blood

OBJECTIVEAnimal model of Qi deficiency and blood stasis was established by muti-factor stimulation in rats.

METHODHealthy SD rats were chronically stimulated randomly by muti-factor methods (chronic sleep deprivation and feed with moderately high lipid and sugar food). Then the indices of hemorheology, plasma total lipids, vasoactive molecules, blood pressure (BP) and ventricular pressure (VP) were measured.

RESULTThe results as well as the analysis of etiology and pathology suggested that model rats could objectively reflect the clinical characteristics of Qi deficiency and blood stasis syndrome. Blood viscosity at low level, plasma content of angiotensin II (Ang II) and endothelin (ET) significantly increased in model rats, while BP and VP significantly decreased (P < 0.05). On the other hand, Buyang Huanwu decoction could lower down the level of AngII in serum and blood viscosity at low level in rats induced by some stimulus, whereas BP and VP elevated significantly (P < 0.05).

CONCLUSIONAnimal model of Qi deficiency and blood stasis induced by muti-factor stimulation including chronic sleep deprivation and feed with moderately high lipid and sugar food could facilitate further study on blood stasis syndrome and screening of Chinese herbal drugs in promoting blood circulation and removing blood stasis.

Animals ; Blood Circulation ; drug effects ; Blood Pressure ; drug effects ; Blood Viscosity ; drug effects ; Disease Models, Animal ; Drugs, Chinese Herbal ; administration & dosage ; Hemorheology ; Humans ; Lipids ; blood ; Male ; Qi ; Random Allocation ; Rats ; Yin Deficiency ; blood ; drug therapy ; etiology ; physiopathology

OBJECTIVETo observe the effects of tetrahydropalmatine, dehydrocorydaline, berberine and palmatine on anoxia and peroxidation injuries in cardiomyocytes, and study the marterial basis of the anti-ischemia effect on myocardium of Rhizoma Corydalis.

METHODNeonatal rat cardiomyocytes were cultured in vitro, and subjected to an anoxia-reoxia and the hydrogen peroxide injury models. The four compounds were added into the culture medium. The cell viability was measured by MTT method to determine the safe concentrations and the anti-hydrogen peroxide injury effects of the compounds. The LDH activity in culture mediums was measured with the enzyme reaction dynamics-monitoring method to value the anti-anoxia injury effects of the compounds.

RESULTAt most up to 500 mg x L(-1), tetrahydropalmatine showed no sinificant effect on the cell viability, while dehydrocorydaline, berberine and palmatine significantly decreased the cell viability, exceeding 6.3, 0.6 and 6.3 mg x L(-1), respectively (P < 0.05 or P < 0.01). Tetrahydropalmatine, dehydrocorydaline, berberine and palmatine significantly inhibited LDH leakage induced by anoxia-reoxia injury, at concentrations of 50-100, 1.25-5, 4 and 30 mg x L(-1), respectively (P < 0.05 or P < 0.01). None of the four compounds showed significant effect on the hydrogen peroxide injury.

CONCLUSIONThe anti-ischemia effect in myocardium of Rhizoma Corydalis is related to the direct protective effects on cardiomyocytes of its components, tetrahydropalmatine, dehydrocorydaline, berberine and palmatine, amomg which tetrahydropalmatine and dehydrocorydaline are the most important, the former with high safety and low efficacy, while the latter with low safety and high efficacy. And the direct protective effects on cardiomyocytes of these four components may be attained through mechanisms other than anti-peroxidation.

Alkaloids ; pharmacology ; Animals ; Animals, Newborn ; Berberine ; pharmacology ; Berberine Alkaloids ; pharmacology ; Cell Hypoxia ; drug effects ; Cells, Cultured ; Hydrogen Peroxide ; pharmacology ; Myocytes, Cardiac ; drug effects ; metabolism ; Rats

OBJECTIVETo explore the therapeutic effects of Rongban Tongmai granules (RBTM) on the atherosclerosis (AS) in quails.

METHODQuails were divided into normal control group and high-fat diet group. Twelve weeks after feeding, 3 quails from normal control group and 8 quails from high-fat diet group were anatomized and confirmed by pathological examination that AS has formed, then the high-fat diet group was randomly divided into 5 subgroups: Model, shujiangzhi 0.004 g x kg(-1) and RBTM (3, 6,12 g x kg(-1)). High fat fodder was stoped. Meanwhile, normal fodder was fed and drugs were administrated by gavage. The levels of the TC, TG, HDL-C, LDL-C in serum were determined at the time points below: Pre-experiment, per-drug administration, 4 weeks after drug administration, 8 weeks after drug administration, 12 weeks after drug administration. After experiment, pathological examination was performed on aorta, bilateral brachiocephalic artery and heart. Meanwhile, the levels of TC, TG and MDA as well as the activity of SOD in liver tissue were determined.

RESULTThe levels of TC, TG, LDL-C, VLDL-C and TC/HDL-C ratio in serum of AS quails were significantly decreased, the levels of TG and MDA in liver were decreased, the thickness and area of the plaque were significantly decreased.

CONCLUSIONRBTM might have effects of modulating blood lipid and improving lipid peroxidation, and also contribute to inhibit the development of AS and accelerate AS regression.

Animals ; Atherosclerosis ; blood ; drug therapy ; pathology ; Cholesterol, HDL ; blood ; Cholesterol, LDL ; blood ; Disease Models, Animal ; Drugs, Chinese Herbal ; administration & dosage ; Humans ; Male ; Quail ; Random Allocation ; Triglycerides ; blood