Cardioprotective effects of tanshinone IIA on myocardial ischemia injury in rats.

Tanshinone IIA (Tan IIA), a derivative of phenanthrenequinone isolated from Salvia miltiorrhiza, has been widely used for treating cardiovascular diseases in China. In the present study, we assessed the effect of Tan IIA on cardiac function, vascular endothelial growth factor (VEGF) expression and angiogenesis on models of myocardial infarction (MI) in rats. The results demonstrated that TanIIA elicited a significantly cardioprotective effect by improving heart function, reducing infarct size, and increasing survival rate in MI rat. Our results offer, for the first time, further insight into Tan IIA promoting angiogenesis and up-regulating VEGF expression in MI rats due to the enhancement of hypoxia-inducible factor 1alpha mRNA expression, and provide a novel target for Tan IIA in the prevention and treatment of myocardial ischemia injury.

Comparison of cardioprotective effects of salvianolic acid B and benazepril on large myocardial infarction in rats.

In the present study, we compared cardioprotective effects of salvianolic acid B (Sal B) and the angiotension-converting enzyme inhibitor, benazepril, in rats with large myocardial infarction (MI). The large MI was produced by coronary artery ligation for 4 weeks in rats. The rats were divided into the following groups: sham operation; MI; MI + Sal B (100 mg/kg by a gavage, once a day for 4 weeks) and MI + benazepril (1 mg/kg by a gavage, once a day for 4 weeks). Echocardiogram, hemodynamic and hemorheological changes, angiogenesis, infarct size and cardiac remodeling, as well as messenger ribonucleic acid (mRNA) of vascular endothelium growth factor (VEGF) were measured. The following similar effects were observed in MI rats treated with Sal B and benazepril: (1) a marked improvement of echocardiographic, hemodynamic and hemorheological parameters, (2) significant reduction of infarct size, (3) significantly attenuated heart hypertrophy, left ventricular (LV) dilatation and fibrosis. The unique effects of Sal B were: angiogenesis and augmented VEGF expression in the border and remote noninfarcted LV area. These results suggest that Sal B and benazepril exerted beneficial cardioprotective effects. However, Sal B enforced some different modality than benazepril, which might improve myocardial microcirculation by augmenting VEGF expression and promoting angiogenesis besides similar effects to benazepril.

[Hepatic and renal injury induced by Radix Aristolochiae or Guanxin Suhe Wan for a long-term in rats].

OBJECTIVE: To evaluate the toxicity of Radix Aristolochiae supplied experimental evidence of rational use of drug in clinic. METHOD: After treatment with small dose Radix Aristolochiae, Guanxin Suhe Wan (with Radix Aristolochiae) and Guanxin Suhe Wan (without Radix Aristolochiae) in different group for a long- term, respectively, the biochemical indicator of PT, ALT, AST, ALB, ALP, Crea and BUN were detected, and the kidney, liver, stomach and urinary bladder were examined by pathologic assaying. RESULT: In Radix Aristolochiae group and Guanxin Suhe Wan (with Radix Aristolochiae) group, all of biochemical indicator were changed significantly, and hepatonecrosis, renal tubular necrosis, gastric carcinoma and bladder carcinoma were discovered. CONCLUSION: Radix Aristolochiae and Guanxin Suhe Wan (with Radix Aristolochiae) can damage kidney and liver, and cause gastric carcinoma and bladder carcinoma by intensive toxicity.

[Nephrotoxicity of Radix Aristolochice and it's substitution material Radix Inulae in rats].

OBJECTIVE: To evaluate the toxicity of Radix Aristolochiae and Radix Inulae, and to supply the toxicity experimental data that Radix Inulae supersedes Radix Aristolochiae in clinic. METHOD: A long dose of Radix Aristolochice and Radix Inulae was given intragastrically to rats for six months, then drug withdrawal for a month. The hematology and biochemical indicators were measured, and the pathologic changes of kidney, liver, stomach and urinary bladder were examined. RESULT: The rats of Radix Aristolochice showed serious toxic responses of renal tubule atrophy and necrosis, meanwhile, the levels of BUN, Cr and NAG were increased obviously. Hepatonecrosis, renal tubular necrosis, gastric carcinoma and bladder carcinoma were discovered with pathologic assaying. But the rats of Radix Inulae did not. CONCLUSION: Radix Aristolochiae could damage kidney and liver, and cause gastric carcinoma and bladder carcinoma by intensive toxicity. Radix Inulae could take the place of Radix Aristolochiae to use in clinic.

[Effects of series of Muskone on heart hemodynamics and myocardial consumption of oxygen in experimental dogs].

OBJECTIVE: To observe the effects of series of Muskone (the muskone includes Slender Dutchmanspipe Root, Inula Root and neither kind of Common Aucklandia Root) on the heart hemodynamics and myocardial consumption of oxygen in experimental dogs, and to explain its pharmacological action on cardiovascular system. METHOD: Arterial blood pressure, coronary blood flow, resistance in coronary artery, total peripheral resistance, work of left artrium and oxygen consumption index of the cardiac muscles were observed in anaesthetic dogs. RESULT: The series of Muskone decreased arterial blood pressure significantly, dilated coronary artery and peripheral arteries significantly, increased coronary blood flow, decreased resistance in coronary artery, improved the work of left artrium, the oxygen availability of cardiac muscles and the complaisance of arteries in cardiac muscles.

[Study on therapeutic effects of series of muskone on myocardial infarction canines].

OBJECTIVE: To observe the effects of the series of Muskone (the Muskone includes Slender Dutchmanspipe Root, Tumuxiang, and not Slender Dutchmanspipe Root) on myocardial ischemia, myocardial infarction and hematological index in experimental canines, and to explain the pharmacological action and characteristic of its therapeutic effect on ischemic heart disease. METHOD: The range and degree of myocardial ischemia was evaluated by epicardial electrogram mapping, and the range extent of myocardial infarction was determined by quantitate histology (N-BT staining method). Meanwhile, the changes of ET, TXB2, 6-Keto-PGF1alpha were determined to study the effects of the series of Muskone on myocardial ischemia, myocardial infarction and hematological index in experimental canines. RESULT: The series of Muskone can improve myocardial ischemia and infarction in experimental canines, and relieve significantly the degree of myocardial ischemia (Sigma-ST) determined by epicardial electrogram mapping, decrease the range of myocardial ischemia (N-ST) determined by epicardial electrogram mapping and decrease infarction zone determined by N-BT staining method. And it has a significant inhibition on activity of ET induced by myocardial ischemia and infarction, and increases 6-Keto-PGF1alpha and 6-Keto-PGF1alpha/TXB2 induced by myocardial ischemia. CONCLUSION: The series of Muskone has significant therapeutic effect on myocardial infarction.

[Study on comparative pharmacology of series of Muskone].

OBJECTIVE: To study the therapeutic effects of the series of Muskone (the Muskone includes Slender Dutchmanspipe Root, Tumuxiang, and not Slender Dutchmanspipe Root) on experimental myocardial infarct and pain in rats. METHOD: Coronary artery ligation was applied for the model of myocardial infarct. Therapeutic effects were evaluated by measuring parameters of histomorphometry, blood plasm of ET, 6- keto-PGF1alpha and TXB2. Intraperitoneal injection acetic was applied for the model of ache, the frequency and eclipse period of writhing were evaluated its effect of resisting pain. RESULT: The Muskone including Radix Aristolociae, the Muskone including Radix Inulae and the Muskone without Radix Aucklandiae all can decrease the area of myocardial infarction in rats, the level of TXB2, ET, and the frequency of writhing significantly. Also it can increase the level 6-keto-PGF1alpha, the ratio of 6-keto-PGF1alpha and TXB2. Single Radix Aristolociae or Radix Inulae only relieved pain. CONCLUSION: The Muskone including Radix Aristolociae, the Muskone including Radix Inulae and the Muskone without Radix Aucklandiae all have significant therapeutic effect on both myocardial infarction and pain, while single Radix Aristolociae or Radix Inulae only can relieve pain.

Effects of Guiyuanfang and autologous transplantation of bone marrow stem cells on rats with liver fibrosis.

AIM: To investigate the therapeutic effects of Guiyuanfang and bone marrow stem cells (BMSCs) on rats with liver fibrosis. METHODS: Liver fibrosis model was induced by carbon tetrachloride, ethanol, high lipid and assessed biochemically and histologically. Liver function and hydroxyproline contents of liver tissue were determined. Serum hyaluronic acid (HA) level and procollagen III level were performed by radioimmunoassay. The VG staining was used to evaluate the collagen deposit in the liver. Immunohistochemical SABC methods were used to detect transplanted BMSCs and expression of urokinase plasminogen activator (uPA). RESULTS: Serum transaminase level and liver fibrosis in rats were markedly reduced by Guiyuanfang and BMSCs. HA level and procollagen III level were also reduced obviously, compared to model rats (HA: 47.18+/-10.97 ng/mL, 48.96+/-14.79 ng/mL; PCIII: 22.48+/-5.46 ng/mL, 26.90+/-3.35 ng/mL; P<0.05). Hydroxyproline contents of liver tissue in both BMSCs group and Guiyuanfang group were far lower than that of model group (1 227.2+/-43.1 microg/g liver tissue, 1390.8+/-156.3 microg/g liver tissue; P<0.01). After treatment fibrosis scores were also reduced. Both Guiyuanfang and BMSCs could increase the expression of uPA. The transplanted BMSCs could engraft, survive, and proliferate in the liver. CONCLUSION: Guiyuanfang protects against liver fibrosis. Transplanted BMSCs may engraft, survive, and proliferate in the fibrosis livers indefinitely. Guiyuanfang may synergize with BMSCs to improve recovery from liver fibrosis.

[The anticancer effect of artesunate and its mechanism].

AIM: To study the anticancer effect of artesunate and its mechanism. METHODS: To observe the effect of artesunate on the growth of solid tumor and the expression of PCNA, Bcl-2 and Bax genes in mice bearing H22 solid hepatic carcinoma. RESULTS: After administration of artesunate (ig, 300 mg.kg-1.d-1 x 7 d), growth of solid tumor was obviously inhibited, the tumor inhibitory rates were 49.1%, 48.7% and 46.6% and 46.6% in 3 experiments. The apoptosis of liver cancer cells were increased. Immunohistochemical staining showed that the number of Bcl-2 protein positive cells were decreased, but the number of Bax protein positive cells were increased. The PCNA positive cells were significantly lower than those in the control group. CONCLUSION: Artesunate showed obvious anticancer activity on H22 hepatic carcinoma bearing mice and undergo apoptosis of liver cancer cells. The mechanism of anticancer effect of artesunate may be related to down-regulation of the expression of PCNA and Bcl-2 genes and up-regulation of the expression of Bax gene.

Beta-aescin: a potent natural inhibitor of proliferation and inducer of apoptosis in human chronic myeloid leukemia K562 cells in vitro.

Beta-aescin, a natural triterpenoid saponin isolated from the seed of Chinese horse chestnut (Aesculus chinensis), is known to generate a wide variety of biochemical and pharmacological effects. In the present study, the authors investigated the anti-proliferative and apoptotic effects of beta-aescin in human chronic myeloid leukemia K562 cell line in vitro. The anti-proliferative effects were detected by CFU-K562 colony formation and cell viability assay. The apoptotic effects were analysed by morphological analysis, annexin V assay, DNA fragmentation assay and flow cytometry DNA content analysis. The results showed that beta-aescin exhibited potent dose- and time-dependent anti-proliferative effects in K562 cells. Morphological evidence of apoptosis, a significant increase of annexin V+ and PI- cells (early apoptotic) and apoptotic DNA fragmentation, were observed in cells treated with beta-aescin. Flow cytometry analysis revealed that beta-aescin could lead to an accumulation of sub G1 population in K562 cells, and suggesting a potential G1 phase accumulation in cell cycle profile of K562 cells. Our findings revealed that beta-aescin is a potent natural inhibitor of proliferation and inducer of apoptosis in K562 cells, and beta-aescin may be a candidate lead compound to explore potential antileukemia drugs.

Effects of fenofibrate and xuezhikang on high-fat diet-induced non-alcoholic fatty liver disease.

1. Fenofibrate and xuezhikang are two types of drugs widely used in the treatment of dyslipidaemia in China. The main purpose of present study was to test the efficacies and explore the potential mechanisms of action of the two lipid-lowering agents on high-fat diet-induced non-alcoholic fatty liver disease (NAFLD). 2. Rats were randomly divided into four groups, with eight rats per group. One group was given normal diet, whereas the other three groups were fed a high-fat diet. Forty-two days later, two of the high-fat diet-fed groups were administered fenofibrate (100 mg/kg, p.o.) and xuezhikang (300 mg/kg, p.o.) for another 42 consecutive days. The other two groups were administered placebo (saline) by gavage. 3. Typical pathological symptoms of NAFLD occurred in the high-fat diet groups. Fenofibrate and xuezhikang treatment markedly improved NAFLD, ameliorating dyslipidaemia and fat accumulation in the liver, improving insulin resistance and ameliorating oxidative stress. Hepatic steatosis, necro-inflammation and collagen deposition were lessened in the drug-treated groups. However, both xuezhikang and fenofibrate failed to reverse hepatomegaly and fenofibrate even aggravated it. Xuezhikang reversed aminotransferase abnormalities, but fenofibrate had less of an effect. 4. The common therapeutic mechanism of action of fenofibate and xuezhikang likely involves inhibition of the hepatic expression of tumour necrosis factor-alpha. Fenofibrate upregulated mRNA levels of peroxisome proliferator-activated receptor (PPAR) alpha in the liver, whereas xuezhikang had no effect on the hepatic expression of PPARalpha and this may explain, in part, their different effects on the NAFLD rats. 5. The results suggest that fenofibrate and xuezhikang may have potential clinical application in the treatment of NAFLD. However, the side-effects of fenofibrate and the underlying constituents of xuezhikang need to be determined and investigated further.

Increased inflammatory factors activity in model rats with experimental autoimmune prostatitis.

Male rats were immunized with prostate tissue homogenate supernate (PTHS) of male rats with complete Freund's adjuvant (CFA) intra dermal in the multiple points and simultaneously immunized with 0.5 ml Pertussis-Diphtheria-Tetanus (PDT) vaccine intra peritonea on 0 and 30th day. At the 45th day after first immunization, animals were sacrificed and a series of examinations such as HE stain, assay of TNF-alpha by ELISA and assay of inducible nitric oxide synthase (iNOS) mRNA by in-situ hybridization (ISH) were taken. We observed that there was a remarkable up-regulation of TNF-alpha expression in the high dosage model group. The results of macropathology, histopathology and iNOS ISH also revealed the same tendency. This experimental procedure is effective to induce chronic abacterial prostatitis (CAP).