Mahuang decoction mitigates airway inflammation and regulates IL-21/STAT3 signaling pathway in rat asthma model.

ETHNOPHARMACOLOGICAL RELEVANCE: Nowadays, bronchial asthma is still a severe disease threatening human health, and it is incumbent upon us to seek effective therapeutic drugs. Mahuang decoction (MHD), a classic famous Chinese prescription, has been used for thousands of years to prevent phlegm from forming, stop coughing and relieve asthma, but the relevant mechanism has not been thoroughly clarified. This study aims to investigate the anti-airway inflammation effect of MHD and the possible molecular mechanism underlying IL21/STAT3 signaling pathway, so as to provide guidance for the treatment of MHD on bronchial asthma. MATERIALS AND METHODS: Specific pathogen free SD rats were randomly divided into 6 groups: normal control group, model group, positive group (Compound methoxyphenamine), MHD-treated groups at doses of 10 ml/kg, 5 ml/kg and 2.5 ml/kg, 10 rats in each group. Except for the normal control group, rats in other groups were sensitized with ovalbumin via introperitoneal injection and challenged with ovalbumin inhalation to trigger asthma model. At 24 h after the last excitation, bronchoalveolar lavage fluid (BALF) of every rat was drawn and the number of inflammatory cells was analyzed using cell counting method. ELISA method was performed to determine the concentrations of TXB2, 6-keto-PGF1α, MMP-9, TIMP-1, IL-2, IL-4, IL-5 and TNF-α in rat serum. The protein expressions of IL-21, IL-21R, STAT3 and p-STAT3 in murine pulmonary tissues were assessed with western blotting analysis. RESULTS: Compared with the control group, the airway wall and airway smooth muscle of murine pulmonary tissues significantly thickened and massive inflammatory cells infiltration occurred around the bronchus in the model group, and the cell counts of WBC and EOS in BALF were also apparently increased, which indicated the rat asthma model was successfully established. MHD or Compound methoxyphenamine not only alleviated the pulmonary inflammatory pathological damages, but also down- regulated the numbers of WBC and EOS in BALF. What's more, the levels of TXB2, MMP-9, TIMP-1, ILs-(2, 4, 5) and TNF-α in rat serum were lessened by the treatment of MHD. In western blotting analysis, treatment with 10 ml/kg or 5 ml/kg MHD markedly declined the increased protein expressions of IL-21, IL-21R, STAT3 and p-STAT3 in lung tissues of asthmatic rats to normal level. CONCLUSION: MHD intervention demonstrated a strong inhibitory action on the secretion of inflammatory mediators as well as the inflammatory cell infiltration in pulmonary tissues of asthmatic rats, and also depressed the protein expressions of IL-21, IL-21R, STAT3 and p-STAT3 in pulmonary tissues. MHD effectively mitigates airway inflammation and regulates the IL-21/STAT3 signaling pathway in rat asthma model.

Antithrombotic effect and mechanism of Rubus spp. Blackberry.

The compounds of Rubus spp. Blackberry (RSB) were isolated and identified by a bioassay-guided method, and their antithrombotic effects and mechanism were investigated with the acute blood stasis rat model. The RSB extract was evaluated by activated partial thromboplastin time (APTT), thrombin time (TT), prothrombin time (PT), and fibrinogen (FIB) assays in vitro. Results indicated that RSB extract exhibited anticoagulant activity. In addition to compounds 1 and 6, the other compounds also exhibited anticoagulant activity in vitro. Therefore, the in vivo antithrombosis effects of RSB extract were investigated by measuring whole blood viscosity (WBV), plasma viscosity (PV), APTT, PT, TT, and FIB. Meanwhile, the levels of thromboxane B2 (TXB2), 6-keto prostaglandin F1α (6-keto-PGF1α), endothelial nitric oxide synthase (eNOS) and ET-1 (endothelin-1) were measured. Results suggested that RSB extract had inhibitory effects on thrombus formation, and its antithrombotic effects were associated with the regulation of vascular endothelium active substance, activation of blood flow and an anticoagulation effect.

Microvascular pathological features and changes in related injury factors in a rat acute blood stasis model.

OBJECTIVE: To examine the microvascular pathological characteristics and changes in related injury factors in a rat model of acute blood stasis. METHODS: A total of 75 Sprague-Dawley rats were divided randomly and equally into a control group and four experimental groups assessed at different times after the induction of stasis (0, 1, 3 or 6 h after stasis) (n = 15). The acute blood stasis model was established through rat tail-vein injection of high-molecular-weight dextran. After Electrocardiograph (ECG) detection at predetermined times (0, 1, 3 and 6 h after induction of stasis), the rats were sacrificed and blood and cardiac samples were harvested for analysis. Hematoxylin-eosin (HE) staining and transmission electron microscopy were used for histopathological detection; an enzyme linked immunosorbent assay (ELISA) was used to detect thromboxane B2 (TXB2) and 6-keto-prostaglandin F1α (6-Keto-PGF1α) concentrations; a real-time polymerase chain reaction (PCR) reaction system was used to detect intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule1 (VCAM-1) mRNA expression; western blotting was used to detect vascular endothelial cadherin (VE-cadherin) protein expression. RESULTS: The ST segment in the ECG showed gradual elevation after induction of stasis and continued elevation at a high level at 3 and 6 h. The HE staining showed changes in myocardial cell necrosis and tissue dissociation after the induction of stasis, along with inflammatory infiltration. Results of transmission electron microscopy showed immediate changes in blood stasis and lumen occlusion in the microvasculature, along with endothelial cell swelling. After the induction of stasis, TXB2 concentrations gradually increased while 6-Keto-PGF(1α) concentrations were immediately significantly reduced. The TXB(2)/6-Keto-PGF(1α) ratio was maintained at a high level. ICAM-1 mRNA expression showed an unstable elevation while VCAM-1 mRNA expression was significantly reduced after the induction of stasis. Compared with the control group, VE-cadherin protein expression increased at 0 and 3 h after the induction of stasis, while no change occurred at 1 and 6 h. CONCLUSION: The pathological manifestations of acute blood stasis are microvascular blood retention, lumen stenosis and even occlusion. The condition is also called "blood coagulation and weep" in Traditional Chinese Medicine. The blood stasis model resulted in the injury and necrosis of endothelial cells and cardiomyocytes, along with the presence of an imbalance of vasomotor factor levels, platelet activation, and increases in the expression of adhesion molecules and endothelial barrier dysfunction, which corresponds to "blood failed to nourish" in Traditional Chinese Medicine.

Anti-myocardial ischemia effect of Syringa pinnatifolia Hemsl. by inhibiting expression of cyclooxygenase-1 and -2 in myocardial tissues of mice.

ETHNOPHARMACOLOGICAL RELEVANCE: The peeled stem of Syringa pinnatifolia Hemsl. (SP) is a traditional medicine in Inner Mongolia, China. The powder form of SP has been widely used for hundreds of years to relieve "He-Yi" related myocardial ischemia independently or in a traditional Chinese medicine preparation. MATERIALS AND METHODS: SP was extracted with 95% and 80% ethanol. Chemical profiling was performed using HPLC-DAD and IT-TOF-ESI-MS analyses. Myocardial ischemia was produced by ligation of the left anterior descending (LAD) coronary artery to evaluate the anti-myocardial ischemia effect of SP. Male C57BL/6 mice were randomly divided into six groups (n=10 per group): a sham group, a model group, groups pretreated with SP at three dosages (20mg/kg, 40mg/kg, and 80mg/kg, intragastrically), and a positive control group (acetylsalicylic acid, ASA, 53mg/kg, intragastrically). Echocardiography was performed to determine heart function by measuring ejection fraction and fractional shortening. The levels of creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH) in serum, and 6-keto-PGF1α and TXB2 both in plasma and in protein homogenate of myocardial tissue were also measured. The levels of cyclooxygenase (COX)-1 and -2 in the heart tissue and their expressions in mouse myocardial tissue were determined using Western blot and an immunofluorescence assay, respectively. Inflammatory cell infiltration and collagen deposition changes in the myocardial ischemic tissue were observed by pathological examination. RESULTS: Intragastric pretreatment with SP produced a dose-dependent increase in cardiac function. SP at 80mg/kg significantly improved the EF (p<0.001) and FS (p<0.01) compared with the model group, as well as the levels of serum CK-MB and LDH decreased obviously (p<0.001), approaching those in the sham group. Besides, an obvious reduction in inflammatory cells infiltration and collagen deposition in the infarcted myocardial tissue was shown in each SP treatment group. In addition, SP increased 6-keto-PGF1α and decreased TXB2 levels in the plasma, whereas the opposite pattern was observed in the protein homogenate from the myocardial tissues at the infarction edge, but keeping balance the ratio of 6-keto-PGF1α and TXB2, which is better than ASA in plasma. The mechanisms is associated with the downregulated expressions of COX-1 (p<0.05) and COX-2 (p<0.001). CONCLUSIONS: Ethanol extract of SP has a protective effect against myocardial ischemia via down regulation of COX-1 and COX-2 expression and by adjusting the ischemia-induced imbalance between 6-keto-PGF1α and TXB2. This study shows substantial evidence to support the clinical application of SP and indicates that such medicine has great potential for treating ischemia-induced heart disease.

[Effects of Electroacupuncture Stimulation of "Neiguan" (PC 6) at Different Frequencies on Plasma Vasoactive Substance Levels in Myocardial Ischemic Reperfusion Rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) stimulation of "Neiguan" (PC 6) at different frequencies on plasma vasoactive substance levels in myocardial ischemia-reperfusion (MIR) injury rats, so as to explore its mechanisms underlying improvement of acute myocardial ischemia. METHODS: A total of 40 Wistar rats were randomized into control, model, high frequency (HF, 120 Hz) and low frequency (LF, 20 Hz) groups (n = 10 in each group). The MIR model was established by occlusion of the anterior descending branch (ADB) of the left coronary artery for 30 min, followed by reperfusion for 40 min. EA (3 V, 120 Hz or 20 Hz) was applied to bilateral "Neiguan" (PC 6) for 50 min immediately after occlusion of ADB. Subsequently, the contents of plasma endothelin (ET), atrial natriuretic peptide (ANP), thromboxane B 2 (TXB2) and 6-Keto-PGF1, were assayed by radioimmunoassay, and the content of serum nitric oxide (NO) was detected by nitrate reductase method. RESULTS: Compared with the control group, the contents of plasma ET, ANP and TXB2 in the model group were significantly increased (P < 0.05), and that of plasma 6-Keto-PGF1α in the model group was notably decreased (P < 0.05), but no significant change was found in serum NO level (P > 0.05). Compared with the model group, the contents of plasma ET, ANP and TXB2 were considerably decreased, and plasma 6-Keto-PGF1α and serum NO contents were obviously increased in both HF and LF groups (P < 0.05). No significant differences were found between the HF and LF groups in plasma ET , ANP, TXB2 and 6-Keto-PGF1α contents (P > 0.05), but the HF EA was markedly superior to the LF EA in up-regulating the content of serum NO (P < 0.05). CONCLUSION: EA stimulation of "Neiguan" (PC 6) can down-regulate the contents of plasma ET, ANP and TXB2 and up-regulate contents of plasma 6-Keto-PGF1α and serum NO in MIR rats, which may contribute to its effect in relieving acute ischemic myocardial injury. The effect of HF EA is better than LF EA in raising blood NO level.

The antithrombotic effect of RSNK in blood-stasis model rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Reduction of Sheng-Nao-Kang decoction (RSNK), composed of Salvia miltiorrhiza Bge., Ligusticum chuanxiong Hort., Astragalus membranaceus (Fisch.) Bunge., Pueraria lobata (Willd.) Ohwi., Paeonia lactiflora Pall. and Panax notoginseng (Burk.) F. H. Chen., is a modified traditional Chinese medicinal formula of Sheng-Nao-Kang pill preparation, which has been investigated its protective effect on focal cerebral ischemia-reperfusion injury in rat in our previous report. AIM OF THE STUDY: To evaluate the antithrombotic effect of RSNK in blood stasis model rats and explore the potential mechanisms. MATERIALS AND METHODS: Subcutaneous injection of norepinephrine and bovine serum albumin combined with ice water bath was used to establish the acute blood stasis rat model. The anticoagulant activities were investigated by measuring activated partial thromboplastin time (APTT), thrombin time (TT), prothrombin time (PT), and the content of fibrinogen (FIB). Meanwhile, the levels of thromboxane A2 (TXA2), prostaglandins I2 (PGI2), endothelial nitric oxide synthase (eNOS) and endothelin (ET) were detected. RESULTS: The treatment of RSNK was able to prolong APTT, TT and PT, and decrease FIB content obviously. Furthermore, it markedly suppressed TXB2 level and up-regulated 6-keto-PGF1α level of the blood-stasis model rats, accompanied with the decrease of T/K. The level of ET and TXA2 in plasma was down-regulated and the levels of eNOS in plasma and PGI2 in serum was up-regulated in RSNK-treated rats compared with model rats (P<0.05). CONCLUSION: The present study suggested that RSNK possessed remarkable antithrombotic property in blood stasis model rats induced by ice water bath and subcutaneous injection of norepinephrine and bovine serum albumin. This property could be associated with its anticoagulation activity, the regulation of active substances in vascular endothelium and maintaining the balance of TXA2 and PGI2.

Prevention of atherosclerosis by Yindan Xinnaotong capsule combined with swimming in rats.

BACKGROUND: Yindan Xinnaotong capsule has been used for treating cardio-cerebrovascular diseases for several decades in China. Exercise training can protect against the development of atherosclerosis. The aim of the present study is to evaluate the joint effect of YXC and exercise on atherosclerosis in rats. METHODS: A combined method involving low shear stress and a high-fat diet was used to establish the atherosclerosis model in rats. Partial ligation of the left common carotid artery was performed, and then the rats were divided into 9 treatment groups according to a 3 × 3 factorial design with two factors and three levels for each factor, swimming of 0, 0.5, 1 h daily and YXC administration of 0, 1, 2 g/kg p.o. daily. Next the interventions of swimming and YXC were executed for 8 weeks. After that, blood samples were collected to determine blood viscosity, plasma viscosity, haematocrit (HCT), fibrinogen (FIB), blood lipid profile (including total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), triglyceride (TG) and high-density lipoprotein-cholesterol (HDL-C)), nitric oxide (NO), 6-keto- prostaglandin (PG) F1α, endothelin (ET) and thromboxane (TX) B2. The common carotid arteries of the rats were harvested to examine pathological changes, wall thickness and circumference, and the expression of SM22αwas assayed via immune-histochemistry. RESULTS: The early pathological changes were observed. The joint effects of YXC and swimming showed significant changes in the examined parameters: (1) decreases in plasma viscosity, blood viscosity and FIB; (2) increases in NO and 6-keto-PGF1α; (3) decreases in ET and TXB2; and (4) decreases in LDL-C and TG. The combination of 2 g/kg YXC and 1 h of swimming led to synergistic decreases in LDL-C and TG. The interactive effect between YXC and swimming was obvious in decreasing wall thickness. Swimming alone was able to up-regulate the expression of SM22α. CONCLUSIONS: In conclusion, this study indicates that the combination of YXC and swimming may prevent atherosclerosis through a synergistic effect between YXC and swimming in improving blood circulation, hemorheological parameters, blood lipids levels and the vascular endothelium in rats. The vascular remodeling may be contributed to the prevention effects on AS by up-regulating SM22α.

Yerba mate (Ilex paraguariensis) improves microcirculation of volunteers with high blood viscosity: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Elevated blood viscosity is a risk factor for atherosclerosis, thrombosis and other cardiovascular events. Our previous studies have suggested that consumption of Yerba mate tea (Ilex paraguariensis) has strong antioxidant and lipid-lowering properties in animals. The in vivo effects of Yerba mate on blood viscosity in humans, however, have not been studied. OBJECTIVE: This study aims to investigate the effect of Yerba mate tea on the reduction of blood viscosity and the improvement of microcirculatory parameters commonly regarded as risk factors for serious cardio and cerebrovascular disorders. METHODS: 142 subjects with high blood viscosity were recruited in this randomized, double-blind, placebo-controlled study. Yerba mate tea or placebo (5 g/day) was administered to different groups for 6 weeks. After treatment, results of hemorheological indexes, nailfold microcirculation, 6-keto-PGF1α and TXB2 and lipid profiles of subjects in the Yerba mate tea group were compared with those in the placebo-receiving group. RESULTS: Parameters of blood viscosity and microcirculation were improved in the subjects from the Yerba mate tea group but not in placebo-receiving patients. After treatment, whole blood viscosity, plasma viscosity and the Equation K value of erythrocyte sedimentation rate (ESRK) decreased significantly in the Yerba mate group. Meanwhile, shape, flow state and nailfold microcirculation appeared positively changed. Specifically, blood flow speeds accelerated gradually and nailfold weighted integral values decreased significantly. Moreover, the vasodilator 6-keto PGF1α increased while the thromboxane TXB2 decreased in serum samples of subjects in the Yerba mate-receiving group. Overall, Yerba mate tea-receiving subjects saw nearly all measured values improve to levels comparable to those characteristic of patients with normal microcirculation. CONCLUSIONS: These results indicate the therapeutic capacity of Yerba mate tea in the treatment of high blood viscosity. Here, Yerba mate tea played a role in the regulation of various indexes of hemorheology, nailfold microcirculation, and the platelet aggregating factors 6-keto-PGF1a and TXB2. The regulation of these might be correlated with reduced blood viscosity and accelerating blood flow. Thus, Yerba mate tea may reduce some key risk-factors of cardiovascular disease. Daily consumption of Yerba mate tea may be a better-tolerated option for individuals with high blood viscosity and microcirculatory disturbance and as such, a novel preventative strategy for patients at-risk for vascular disease.

[Comparative study on effects of Rubiae Radix et Rhizoma and carbonized Rubiae Radix et Rhizoma on acute blood stasis rat model].

OBJECTIVE: To observe the effects of Rubiae Radix et Rhizoma (RRR) and carbonized Rubiae Radix et Rhizoma (CRRR) on the acute blood stasis rat model, and reveal their differences in efficacy. METHOD: The acute blood stasis model was induced by subcutaneously injecting adrenaline hydrochloride and soaking in ice water. Yunnan Baiyao was used as the positive control drug, and administered for consecutively seven days. This model was adopted to observe the effect of high, middle and low dose RRR and CRRR groups on hemorheology, thrombin activity, and blood platelet system. RESULT: RRR could significantly reduce the wholeblood viscosity and plasma viscosity of blood stasis rats under different shear rates, and showed certain two-way regulating function in hemostasis. It also showed certain effect on ADP-induced platelet aggregation rate, but which was lower than CRRR. CRRR achieved the main hemostatic mechanism by stimulating intrinsic and extrinsic blood coagulation and fibrinogen, and could significantly enhance the platelet aggregation rate of rats in the acute blood stasis model (P <0. 01). CONCLUSION: RRR had the effect of removing blood stasis and hemostasis, while CRRR mainly has the hemostatic effect. This further demonstrates the traditional processing theory of "promoting blood circulation with crude herbs and stopping bleeding with processed herbs".

[Effects of paeoniflorin on cerebral blood flow and the balance of PGI2/TXA2 of rats with focal cerebral ischemia-reperfusion injury].

This study is to investigate the effects of paeoniflorin on cerebral blood flow and the balance of PGI2/TXA2 of rats with focal cerebral ischemia-reperfusion injury. A total of 72 SD rats (3) were randomly divided into 6 groups: sham operation group, cerebral ischemia-reperfusion model group (I/R gourp), low (10 mg.kg-1), middle (20 mg.kg-1) and high (40 mg.kg-1) doses of paeoniflorin groups and nimrnodipine group. Focal cerebral ischemia in rats was made by inserting a monofilament suture into internal carotid artery for 90 min and then reperfused for 24 h. The effects of paeoniflorin on neurological deficit scores and the infarction volume of brain were detected. Relative regional cerebral blood flow (rCBF) was continuously monitored over ischemic hemispheres by laser-Doppler flowmetry (LDF). The expression of COX-2 in hippocampal CAl region was estimated by immunohistochemistry and the contents of prostacyclin I2 (PGI2), thromboxane A2 (TXA2), and ratio of PGIJ2/TXA2 in serum were measured by ELISA kits. Paeoniflorin significantly ameliorated neurological scores, reduced the infarction volume, and increased regional cerebral blood flow relative to the I/R group. In addition, paeoniflorin could inhibit COX-2 expression and the release of TXA2 and prevent the downregulation of PGI2 induced by I/R injury. The neuroprotective effects of paeoniflorin against focal cerebral ischemia-reperfusion rats might be attributed to improve the supply of injured hemisphere blood flow and adjust the balance between PGI2/TXA2.

Comparative study between Ephedra sinica Stapf and Fructus Schisandrae Chinensis on ET-1 and 6-keto-prostaglandin F1α in rats with idiopathic pulmonary fibrosis.

The aim of this study was to evaluate differences in the effects of Ephedra sinica Stapf and Fructus Schisandrae Chinensis on angiogenesis in the treatment of bleomycin-induced rat idiopathic pulmonary fibrosis. The rat models were created using bleomycin. The animals were divided into six groups: model, control, Ephedra alone, Schisandrae alone, combination of Ephedra and Schisandrae, and hydrocortisone alone. The treatments were administered for 28 days. After 7 and 28 days, the rats were sacrificed for pathological morphology examination, microvascular density determination, and angiogenesis-related cytokine examination. The Ephedra and hydrocortisone groups demonstrated significantly reduced alveolitis and pulmonary fibrosis grades compared with the model group (P < 0.05). The number of blood vessels in the Ephedra group was higher than that in the Schisandrae and combination therapy groups. At 7 days, the expression level of endothelin (ET)-1 in the model group was significantly higher than that in the normal group (P < 0.01). The level of 6-keto-prostaglandin F1α (6-keto-PGF1α) in the treatment group increased, and there were significant differences between the Ephedra group and the combination therapy and normal groups (P < 0.05). Ephedra inhibited the increase in the lung coefficient. The combination therapy prevented pulmonary artery injury and angiogenesis of the arteries by reducing the level of ET-1 and promoting the level of 6-keto-PGF1α in the blood. Ephedra and Schisandrae prevented alveolitis and the development of pulmonary fibrosis.

Effects of Cydonia oblonga Miller extracts on blood hemostasis, coagulation and fibrinolysis in mice, and experimental thrombosis in rats.

INTRODUCTION: Cydonia oblonga Miller (COM) is traditionally used in Uyghur medicine for the prevention of cardiovascular disease. The present study is designed to explore the effects of COM extracts on models and markers of thrombosis and related biomarkers. MATERIALS AND METHODS: 20, 40, 80 mg/kg/day COM aqueous extracts and 5mg/kg/day aspirin, orally for 14 days were compared to untreated controls in mice on bleeding and clotting times, using the tail cutting and glass slide methods and for death rates in collagen-epinephrine pulmonary thrombosis, thrombolysis in vitro and euglobulin lysis time (ELT). In rats, common carotid artery FeCl3-induced thrombus and inferior vena cava thrombosis occlusion time, plasma concentrations of thromboxane B2 (TXB2) and 6-keto-prostaglandine F1α (6-keto-PGF1α) were measured. RESULTS AND CONCLUSION: Compared to controls, COM extracts dose-dependently prolonged bleeding by 2.17, 2.78 and 3.63 times, vs. aspirin 2.58, and the clotting time by 1.44, 2.47 and 2.48 times, vs. aspirin 1.91. COM reduced pulmonary embolus mortality by 27, 40 and 53%, vs. 47% for aspirin. COM dose-dependently increased thrombolysis by 45, 55 and 63%, vs. 56% for aspirin, and shortened ELT to 71, 61 and 43%, vs. 43% for aspirin. In rats, venous occlusion time was prolonged. Arterial and venous thrombus weights were dose-dependently reduced in COM groups. TXB2 decreased and 6-keto-PGF1α increased with COM and aspirin, with an association between 6-keto-PGF1α/TXB2 and arterial or venous thrombus weight for all products, and for occlusion time with COM but not for aspirin. CONCLUSION: We confirm the experimental effects of COM on hemostasis and thrombosis. Further exploration of putative clinical effects appear justified.

Yeast exposure in the preparation of steamed rehmannia root improving its effects on alloxan-induced diabetic rats.

ETHNOPHARMACOLOGICAL RELEVANCE: The root of Rehmannia glutinosa (Gaertn.) DC. has been used in China for more than 2000 years to treat various diseases including diabetes mellitus (DM) and its complications. Steamed rehmannia root (SRR) is one of the mainly used forms. During its preparation, the material has the chance to be exposed to microorganisms, particularly yeast. The aim of this study is to verify the effect of SRR on diabetes complications and the necessity of yeast exposure. MATERIALS AND METHODS: Water extract of SRR was incubated with alcohol yeast to obtain fermented SRR (FSRR). Alloxan-induced diabetic rats were administrated with medicated animal chows for 8 weeks. Urine volume, fasted blood glucose and food intake were monitored, and open field test and tail immersion test were conducted in the last week, plasma and urine samples were subjected to biochemical examinations. RESULTS: In DM rats, defecation in open field test was found reduced, and tail flick latency in tail immersion test increased. In the meantime, urinary excretions of Na(+), K(+), aldosterone, albumin and creatinine increased, and plasma concentrations of Na(+), K(+) and creatinine reduced and those of aldosterone, TXB2/6-Keto-PGF(1α) and urea nitrogen elevated. Most of these indicators were significantly improved by FSRR administration, but the effects of SRR were relatively inferior in several aspects. However, SRR and FSRR could not improve the typical symptoms of DM. CONCLUSIONS: Our data demonstrated that both SRR and FSRR have no obvious hypoglycemic effect, but have the potential to prevent the onset and development of diabetes complications, and this function can be improved by yeast exposure.

Effects of an aqueous extract of Crataegus pinnatifida Bge. var. major N.E.Br. fruit on experimental atherosclerosis in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Atherosclerosis (AS) can result in severe cardiovascular diseases. Early indications of AS include disorders in lipid metabolism, inflammatory responses, and endothelial dysfunction. Statins are the preferred drugs for stabilizing atherosclerotic plaques because of their lipid-lowering, anti-inflammation and endothelial-protection activities. However, they can exhibit side effects and are effective in only one-third of patients. Many natural products (especially traditional Chinese medicines (TCMs)) possessing similar lipid-lowering, anti-inflammation and antioxidant activities are of interest in many studies exploring new AS drug therapy. The widely distributed hawthorn is used to prevent and cure heart disease not only in China but also in the United States and several European countries. For example, the fruit of Crataegus pinnatifida Bge. and Crataegus pinnatifida Bge. var. major N.E.Br. (a commonly used hawthorn fruit in China) is used in combination with other TCMs to treat AS. Studies have also shown that the water extracts of these two hawthorn fruits are effective against hyperlipidemia by lowering lipid levels, reducing endothelial dysfunction, and inhibiting inflammation. The aim of the study is to investigate the effect and possible mechanisms of the aqueous extract of Crataegus pinnatifida var. major on AS rats. MATERIALS AND METHODS: The fruit of Crataegus pinnatifida var. major was extracted with 70% ethanol; the ethanol extract was chromatographed on a D101 macroporous resin to obtain a sugar-free aqueous extract (AECP). Atherosclerotic rats were fed a high-fat diet and injected with vitamin D3 and ovalbumin. Rats were divided into five groups: normal, model, model plus simvastatin, model plus low-dose AECP, and model plus high-dose AECP. AECP and simvastatin were administered (via the intragastric route) to AECP groups and the simvastatin group. For normal and model groups, water was given for 4 weeks. After 12 weeks, levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein-cholesterol (LDL-C) and high-density lipoprotein-cholesterol (HDL-C) in blood were measured by an automatic biochemistry analyzer. Serum concentrations of interleukin (IL)-1ß, IL-8, nitric oxide (NO), endothelin (ET), 6-keto-prostaglandin F1α (6-keto-PGF1α) and thromboxane B2 (TXB2) were determined by radioimmunoassay (RIA). Serum concentrations of C-reactive protein (CRP) and IL-18 were measured by enzyme-linked immunosorbent assay (ELISA). Pathological changes in arteries were observed using an optical microscope and the intima-media thickness (IMT) calculated. Cholesterol deposition was evaluated by filipin staining. Chemical ingredients in AECP were analyzed by qualitative and quantitative means by high-performance liquid chromatography (HPLC). RESULTS: AECP significantly reduced the levels of TC, TG and LDL-C but increased HDL-C levels. It also decreased the concentrations of CRP, IL-1ß, IL-8 and IL-18. AECP increased levels of ET and TXB2 but increased 6-keto-PGF1α levels. Histopathological examination showed that AECP inhibited pathological changes in the arteries of AS rats and reduced IMT. Chemical analysis suggested that the main components of AECP were chlorogenic acid, procyanidin B2, (-)-epicatechin, rutin and isoquercitrin. CONCLUSIONS: These data suggest that AECP can inhibit AS progression in high-fat-diet-fed rats. Possible mechanisms of action include improvement of lipid metabolism, decrease in inflammatory cytokine responses, and protection of the endothelium.

[Effects of electro-acupuncture at Zusanli point on gastric and intestinal blood flow in rats with acute necrotizing pancreatitis].

OBJECTIVE: To investigate the effects of electro-acupuncture (EA) at Zusanli point on gastric and intestinal blood flow and serum endothelin-1(ET-1), nitricoxide(NO), thromboxaneB2 (TXB2), 6-keto-prostaglandin F1alpha (6-K-PGF1alpha) in rats with acute necrotizing pancreatitis (ANP). METHODS: Thirty-six male Sprague Dawley (SD) rats were randomly divided into sham operation (sham), ANP and EA groups (n = 12). ANP model was induced by retrograde injection of 5% sodium taurocholate into pancreaticobiliary. EA was applied to Zusanli for 30 min at 2 h and 6 h after the operation in EA group. Gastric and intestinal mucosal blood flow was measured by laser doppler flowmetry (LDF) at 12 h and 24 h after operation, while the levels of serum ET-1, NO, TXB2 and 6-K-PGF1alpha were detected. RESULTS: The gastric and intestinal blood flow in ANP rats were significantly lower than those in the sham group (P < 0.05), but those of EA groups were higher than those in ANP groups (P < 0.05). The serum ET-1, NO and ET-1/NO levels in ANP group were increased when compared with SO group (P < 0.05). After the electro-acupuncture treatment at Zusanli point, the levels of ET-1, NO and ET-1/N were decreased, and there were significant differences of ET-1 (at 12 h, 24 h), NO (at 12 h) and ET-1/NO (at 24 h) between EA and ANP group (P < 0.05). The levels of serum TXB2, 6-K-PGF1alpha and TXB2/6-K-PGF1alpha in ANP group were also increased (P < 0.05), but those in EA group were decreased, and there were significant differences of TXB2 (at 12 h, 24 h), 6-K-PGF1alpha (at 12 h) and TXB2/6-K-PGF1alpha (at 24 h) compared with ANP groups (P < 0.05). CONCLUSION: Electro-acupuncture at Zusanli point can significantly improve the gastric and intestinal mucosa blood flow in ANP rats, which may be related to the regulation of serum ET-1, NO, TXB2, 6-K-PGF1alpha.

Inhibitory effects of Qushuanling Capsule () on thrombus formation and platelet aggregation in rats.

OBJECTIVE: To investigate the effects of Qushuanling Capsule ( 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 B(2) (TXB(2)) 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 TXB(2) and 6-keto-PGF1α in 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.

[Effect of electroacupuncture at different frequencies on serum estradiol and progesterone levels in late-stage pregnancy rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) at different frequencies on serum estradiol (E2), progesterone (P), thromboxance B2 (TXB2), 6-Keton-prostaglandin F 1 alpha (6-keto-PGF1alpha) contents in late pregnancy rats so as to study its mechanisms underlying labor promotion. METHODS: A total of 66 late-stage pregnant Wistar rats were randomly divided into 6 groups: normal control, late-pregnancy model (model), 2 Hz-EA, 20 Hz-EA, 50 Hz-EA and 100 Hz-EA groups, with 11 rats in each group. On the 19th day after pregnancy, EA (2 Hz, 20 Hz, 50 Hz, 100 Hz, 0.1 mA) was applied to bilateral "Hegu" (LI 4) for 20 min first and to bilateral "Sanyinjiao" (SP 6) for 5 min afterwards. Serum E2, P, TXB2 and 6-keto-PGF1alpha contents were assayed by radioimmunoassay, and the ratios of E2/P and TXB2/6-keto-PGF1alpha were calculated. RESULTS: Compared to the normal control group, serum E2 contents in 2 Hz-EA, 20 Hz-EA, 50 Hz-EA and 100 Hz-EA groups were increased significantly (P < 0.001, P < 0.01, P < 0.05). Compared to the model group, serum E2 levels in the 2 Hz-EA and 20 Hz-EA groups were up-regulated further significantly (P < 0.05). Comparison among the four EA groups showed that serum P level in the 100 Hz-EA group was significantly higher than those in the 20 Hz-EA and 50 Hz-EA groups (P < 0.05). Compared to the normal control group, the contents of serum TXB2 and the ratios of E2/P in both 2 Hz-EA and 50 Hz-EA groups were significantly higher (P < 0.05, P < 0.001, P< 0.01). CONCLUSION: Both 2 Hz and 20 Hz EA can effectively increase serum E2 content, and 2 Hz and 50 Hz EA can raise serum TXB2 and E2/P levels in late pregnancy rats, which may contribute to their effects in strengthening the uterine contractility to promote labor by regulating hormone secretion.

[Effects of extracts of Radix Scrophulariae on blood pressure in spontaneously hypertensive rats and the underlying mechanisms].

OBJECTIVE: To explore the effects of extracts of Radix Scrophulariae (ERS) on blood pressure, vasoconstrictors and morphology of artery in spontaneously hypertensive rats (SHRs). METHODS: Fifty SHRs were randomly divided into SHR, SHR plus 40 mg/kg of captopril, SHR plus 70 mg/kg of ERS, SHR plus 140 mg/kg of ERS and SHR plus 280 mg/kg of ERS groups. Wistar-Kyoto (WKY) rats were randomly divided into two groups, namely, WKY and WKY plus 140 mg/kg of ERS groups. The rats were orally administered with the corresponding drugs or drinking water once a day for 20 weeks. The blood pressure was determined every three weeks. At the 21st week, the concentrations of noradrenaline (NA), angiotensin II (Ang II), thromboxane B(2) (TXB(2)) and 6-keto-prostaglandin F(1α) in serum and endothelin-1 (ET-1) were detected by enzyme-linked immunosorbent assay. The morphological changes in abdominal aorta were observed under an optical microscope with hematoxylin and eosin staining. The ratio of intima-media thickness/lumen radius of abdominal aorta was calculated. RESULTS: ERS significantly lowered the blood pressure of SHRs from the 3rd to the 21st week; ERS also reduced the levels of NA, Ang II, ET-1 and TXB(2), decreased the intima-media thickness of abdominal aortal wall and improved the morphological changes in abdominal aorta in SHRs. In addition, ERS did not significantly change blood pressure and vasoactive substances in WKY rats. CONCLUSION: ERS possesses beneficial effects in inhibiting hypertension and attenuating arteriosclerosis. The underlying mechanism may be associated with restraining the release of vasoconstrictors, such as NA, Ang II, ET-1 and TXB(2).

[Effects of the effective components group of xiaoshuantongluo formula on rat acute blood stasis model].

Effects of the effective components group of Xiaoshuantongluo formula (XECG) on rat acute blood stasis model were studied under the guidance of the concept of effective components group. Rat acute blood stasis model was induced by subcutaneous injection of epinephrine combined with ice water bath. Hemorheology indices such as whole blood viscosity, plasma viscosity, erythrocyte aggregation index and platelet aggregation rate; coagulation parameters including PT, APTT, TT and FIB; 6-keto-PGF1alpha, TXB2 and D-dimer levels were determined to evaluate the effects of XECG. The results showed that XECG significantly reduced ADP-induced platelet aggregation, but showed little influence on the whole blood viscosity, plasma viscosity and erythrocyte aggregation rate. XECG extended PT and TT slightly, but had no effects on APTT and FIB content. D-dimer levels significantly decreased after administration of XECG with a little decrease of TXB2, but the content of 6-keto-PGF1alpha did not change significantly. The results suggest that the role of XECG of anti-aggregation is more prominent.

[Effects of two different extracts of total saponins from Cicer arietinum on kidney of T2DM rats].

Protective effects of two different extracts of TSCA (total saponins from Cicer arietinum) were studied on kidney of T2DM rats. The diabetic model group was established with high calorie feeding and small dose injection of streptozotocin (STZ, 45 mg x kg(-1)). DM rats were randomly assigned to model group (feed with propylene glycol 1 mL/100 g), TSCA high dose group (300 mg x kg(-1)), TSCA low dose group (100 mg x kg(-1)) and normal control group (feed with propylene glycol 1 mL/100 g). After four weeks treatment with TSCA I and II, the levels of FPG FIns, BUN, Scr, ATII, ET-1, TXB2 and 6-keto-PGF1alpha in blood and the activities of SOD, GSH-PX and MDA in kidney were analyzed by biochemical methods. After four weeks treatment with TSCA II, the levels of FPG FIns, BUN, Scr, ATII and ET-1 were reduced significantly; and the ratios of TXB2 to 6-keto-PGF1alpha and SOD were effectively alleviated in TSCA II group. While there is no significant change on FPG and BUN in comparison to the rats treated with TSCA I, Scr, ATII, ET-I, GSH-PX and SOD were alleviated. The results suggest that TSCA II could be used to reduce FPG and FIns. According to the result of vasoactive substances index, TSCA II is more effective than TSCA I on renal protection of DM rats.