Pharmacodynamics and metabonomics study of Tianma Gouteng Decoction for treatment of spontaneously hypertensive rats with liver-yang hyperactivity syndrome.

ETHNOPHARMACOLOGICAL RELEVANCE: Essential hypertension is a prevalence chronic cardiovascular disease, which is treated by traditional Chinese medicine (TCM) in China. Metabolomics approach has achieved more attention in pharmacology studies of natural products. Tianma Gouteng Decoction (TGD) is effective for the therapeutic of hypertension in China. We aimed to investigate antihypertension effect of TGD on spontaneous hypertension rat (SHR) with live-Yang hyperactivity hypertension (Gan Yang Shang Kang, GYSK) and explore the mechanism by metabolomics method. MATERIALS AND METHODS: After establishing the GYSK-SHR model by giving aconite decoction, rats were randomly divided into four groups including model group, TGD qd group (66.88 mg/kg, once a day), TGD bid group (33.44 mg/kg, twice a day), TGD tid group (22.29 mg/kg, three times a day). Blood pressure (BP) and indexes of renin-angiotensin-aldosterone system (RAAS system) were measured. Metabolic profiling of rat plasma samples was performed by UPLC-Q-TOF/MS, which was analyzed with principal component analysis (PCA) and partial least-squares-discriminate analysis (PLS-DA) to explore the relationship between metabolic pathways and hypertension. RESULTS: To better explain the role of TGD on hypertension, we detected three different frequencies of TGD treatment with equal dosage. TGD reduced the BP in GYSH-SHR model and regulated the serum levels of NE, Ang II, ET, 5-HT, CRP, RENIN and ALD especially at TGD bid group. By UPLC-Q-TOF/MS analysis, we found 47 potential biomarkers in GYSK-SHR rats from the plasma metabolites, among which 15 biomarkers were regulated by TGD. Consisted with the antihypertension activity, TGD bid group showed the significantly moderating effect on the regulating biomarkers. CONCLUSIONS: TGD exhibited the antihypertensive activity at the frequency of administration twice a day, which had the association with RAAS system and mediated 15 biomarkers by regulating metabolisms of glycerol phospholipid, sphingomyelin, energy and amino acid.

Preventive Effect of Lactobacillus fermentum CQPC03 on Activated Carbon-Induced Constipation in ICR Mice.

Background and objectives: Paocai (pickled cabbage), which is fermented by lactic acid bacteria, is a traditional Chinese food. The microorganisms of Paocai were isolated and identified, and the constipation inhibition effect of one of the isolated Lactobacillus was investigated. Materials and Methods: The 16S rDNA technology was used for microbial identification. A mouse constipation model was established using activated carbon. After intragastric administration of Lactobacillus (108 CFU/mL), the mice were dissected to prepare pathological sections of the small intestine. Serum indicators were detected using kits, and the expression of small intestine-related mRNAs was detected by qPCR assay. Results: One strain of Lactobacillus was identified and named Lactobacillus fermentum CQPC03 (LF-CQPC03). Body weight and activated carbon propulsion rate were all higher in mice intragastrically administered with LF-CQPC03 compared with the control group, while the time to the first black stool in treated mice was lower than that in the control group. Serum assays showed that gastrin (Gas), endothelin (ET), and acetylcholinesterase (AchE) levels were significantly higher in the LF-CQPC03-treated mice than in the control group, while somatostatin (SS) levels were significantly lower than in the control mice. Mouse small intestine tissue showed that c-Kit, stem cell factor (SCF), and glial cell-derived neurotrophic factor (GDNF) mRNA expression levels were significantly higher in the LF-CQPC03 treated mice than in control mice, while transient receptor potential cation channel subfamily V member 1 (TRPV1) and inducible nitric oxide synthase (iNOS) expression levels were significantly lower in the LF-CQPC03 treated mice than in control mice. Conclusions: There is a better effect with high-dose LF-CQPC03, compared to the lower dose (LF-CQPC03-L), showing good probiotic potential, as well as development and application value.

Pharmacodynamic action and mechanism of Du Liang soft capsule, a traditional Chinese medicine capsule, on treating nitroglycerin-induced migraine.

ETHNOPHARMACOLOGICAL RELEVANCE: Du Liang soft capsule (DL) is a traditional Chinese medicine for treating migraines; it is made from two Chinese herbs, including LigusticumstriatumDC., root; Angelica dahurica (Hoffm.) Benth. & Hook.f. ex Franch. & Sav., root. AIM OF THE STUDY: In the present study, we aimed to elucidate the pharmacodynamic action of DL and its mechanism in an animal model of migraines induced by glyceryl trinitrate (GTN). MATERIALS AND METHODS: Sixty rats were randomly divided into six groups, including a normal control group, model control group, positive group (Sumatriptan 0.006gkg-1), and three DL groups (0.44, 1.31 and 3.93gkg-1). All rats were intragastrically treated with the corresponding treatment for 7 consecutive days, and they were subcutaneously injected with GTN (10mgkg-1) 30min after the last treatment, except in the normal control group. After model establishment, the behaviors of all rats, including head scratching, cage climbing, and the development of red ears were observed continuously by digital camera every 30min for 3h. Four hours after GTN treatment, all rats were anaesthetized and the blood and tissue samples were collected. Plasma calcitonin gene related to peptide (CGRP) and endothelin (ET) levels were measured using the radioimmunoassay method, and serum NO was determined by the colorimetric method. Afterwards, the brainstem tissues were dissected and washed with physiological saline, and divided evenly into two parts. One part was used to test the monoamine levels, including levels of 5-hydroxytryptamine (5-HT), norepinephrine (NE) and dopamine (DA), by the fluorometric method, and the other part was used to determine the nuclear factor kappaB (NF-κB) p65, nuclear c-fos, inducible nitric oxide synthase (iNOS), interleukin (IL)-1ß (IL-1ß), and cyclooxygenase-2 (COX-2) levels by Western blot analysis. RESULTS: In the pharmacodynamic action assay, DL (1.31 and 3.93gkg-1) greatly improved the abnormal behaviors of migraine rats, including head scratching and cage climbing, and the development of red ears. In the mechanism assay, compared with the control group, the plasma CGRP and serum NO levels and the brainstem 5-HT, NE and DA levels in the DL administration groups were significantly decreased; and the plasma ET levels were remarkably increased. Moreover, down-regulation of NF-κB p65, c-fos and pro-inflammatory cytokines, including iNOS, IL-1ß and COX-2 in the brainstem in the DL administration groups were observed by Western blot analysis. CONCLUSIONS: The above results suggested that DL has a therapeutic effect on migraines, and its mechanism may be related to adjusting the level of neurotransmitters and vasoactive substances, consequently relieving neurogenic inflammation.

[Impact of prostaglandin F2α and endothelin, pulsation index and resistance index of uterine artery blood flow on dysmenorrhea patients of cold stagnation and blood stasis syndrome with Dingkun Dan].

This research apply Dingkun Dan to treat patients with dysmenorrhea of cold stagnation and blood stasis syndrome. This study observed its effectiveness and safety of the treatment of the disease and its influence on the serum prostaglandin F2α, endothefin, pulsatility index and resistant index of uterine artery blood, to explore the possible mechanism of effect of Dingkun Dan in the treatment of dysmenorrhea and provide scientific basis for clinical application. The 75 patients with dysmenorrhea of cold stagnation and blood stasis who met the inclusion criteria, were divided into treatment group (n=37) and control group (n=38) by using random number remainder grouping method. In the treatment group patients were treated with Dingkun Dan, the other group were given Fuke Zaizao Jiaonang. Two groups have same time to take the medicine, three days prior to the menstruation for ten days. Medication for three menstrual cycles was seen as a course of treatment. To observe and compare the two groups of patients before and after treatment VAS score, syndrome integral, serum levels of prostaglandin F2α and endothelin, pulsation index and resistance index of uterine artery blood flow and related safety index changes. Finally makes statistical analysis. It has been identified that, Treatment group and control group can reduce pain symptom of dysmenorrhea patients and improve the syndromes scores, compare with control group, effect of the treatment group is more significant(P<0.01). VAS pain curative effect: the treatment group and control group total effective rate respectively were, 97.22%, 69.44%, markedly effective rate were 83.33%, 30.56%, comparison between two groups, treatment group is better than that of control group(P＜0.01). Syndromes curative effect: the treatment group and control group total effective rate respectively were 97.22%, 94.44%, markedly effective rate was 66.67%, 2.78%, respectively. The comparison between two groups, the total effective rate has no obvious difference, but markedly effective rate of treatment group is better than that of control group(P＜0.01). The treatment group can significantly reduce the patients' serum level of prostaglandin F2α(P<0.01), but no obvious difference was found in the control group before and after treatment. Both groups can significantly reduce the serum level of endothelin(P<0.01), comparison between two groups, the treatment group is more significant(P<0.01).Both treatment group and control group were significantly lower left and right pulsation index and resistance index of uterus artery blood flow(P<0.01). Between groups to compare the effect, the treatment group is more significant(P<0.01). Both treatment group and control group in the security check before and after treatment found no significant anomalies. Dingkun Dan in treating dysmenorrhea with cold stagnation and blood stasis syndrome seems to have remarkable clinical curative effect and safety, which may be achieved by significantly reducing the serum level of prostaglandin F2αand endothefin of the patients, and reducing the pulsation index and resistance index of uterine artery blood flow of the patients, to improve uterine artery condition of blood, and correcting local tissue ischemia to relieve pain.

[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.

[Effect of electroacupuncture and moxibustion preconditioning on blood endothelin and creatine kinase contents and myocardial HSP 70 expression in rabbits with myocardial ischemia-reperfusion injury].

OBJECTIVE: To observe the effect of electroacupuncture (EA) and moxibustion (Moxi) preconditioning of bi- lateral "Neiguan" (PC 6) on plasma endothelin (ET) and serum creatine kinase (CK) contents and myocardial hot shock protein 70 (HSP 70) expression in myocardial ischemia-reperfusion injury (MIRI) rabbits, so as to revel their mechanisms underlying prevention of myocardial ischemia. METHODS: A total of 72 New Zealand rabbits were randomly divided into sham operation, MIRI model, EA preconditioning and Moxi preconditioning groups (n = 18/group). Each group was further divided into 0 h, 24 h and 48 h (time-point) subgroups (n=6 in each subgroup). The MIRI model was established by occlusion of the anterior descending branch of the left coronary artery for 40 min and reperfusion for 60 min. The contents of plasma ET and serum CK were detected by ELISA, and myocardial HSP 70 expression was detected by immunohistochemistry. EA and Moxi preconditioning were respectively applied to bilateral PC 6 for 20 min, once daily for 5 days. RESULTS: Following MIRI, contents of plasma ET and serum CK contents were significantly increased at 0 h, 24 h and 48 h in comparison with the sham group (P<0.01, P<0.05), while myo- cardial HSP 70 expression at the 3 time-points was moderately increased (P>0.05). Compared with the model groups, plasma ET contents at both 24 h and 48 h in the EA preconditioning group and at 48 h in the Moxi preconditioning group, CK contents at both 24 h and 48 h only in the EA preconditioning group were significantly down-regulated (P<0.01, P<0.05). Myocardial HSP 70 expression levels in the EA and Moxi preconditioning groups were considerably up-regulated at the three time-points in comparison with the model group(P<0.05, P<0.01). CONCLUSION: Acupuncture and moxibustion pretreatment may suppress MIRI-induced increase of plasma ET and serum CK and up-regulate myocardial HSP 70 protein expression in MIRI rabbits, suggesting a preventive protection action on ischemic myocardium.

Effect of Cydonia oblonga Mill. leaf extracts or captopril on blood pressure and related biomarkers in renal hypertensive rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Cydonia oblonga Mill. (COM) is used in traditional Uyghur medicine to treat or prevent cardiovascular disease. In a previous study COM leaf extracts were found to be active in renal hypertensive rats (RHR). The present study tests the dose-dependence of the effect of ethanol leaf extracts on hypertension and on biomarkers associated with blood pressure control, such as angiotensin-II (AII), plasma renin activity (PRA), apelin-12 (A), endothelin (ET) and nitric oxide (NO), compared to captopril. METHODS: Two-kidney one-clip (2K1C) Goldblatt model rats were divided randomly into six groups: sham, model, captopril 25 mg/kg, COM leaf extract 80, 160 and 320 mg/kg (n=10 each). Drugs were administered orally daily for eight weeks. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured before treatment and every 2 weeks. Blood and kidney samples were collected after the last treatment to measure AII, PRA, A, ET and NO. RESULTS: RHR had increased blood pressure, AII, A, PRA, ET and decreased NO. Treatment with captopril reduced blood pressure, AII, A, PRA, and ET, though not quite to normal values. COM leaf extracts significantly and dose-dependently reduced blood pressure, AII, A, RA and ET, whereas NO was increased. The highest dose of COM had the same effects as captopril. CONCLUSION: The effects of COM extracts on blood pressure and biomarkers were dose-dependent and at the highest dose similar to those of captopril. This suggests an action of COM on the renin-angiotensin system, which could explain its antihypertensive effect.

Effect of peroxisome proliferator-activated receptor gamma agonist on heart of rabbits with acute myocardial ischemia/reperfusion injury.

OBJECTIVE: To explore protective effect of rosiglitazone on myocardial ischemia reperfusion injury. METHODS: A total of 48 male SD rats were randomly divided into control group (A), I/R group(B), high dose of rosiglitazone (C), low dose of rosiglitazone (D). Plasm concentration of creatine kinase (CK), CK-MB, hsCRP, Superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), nitric oxide (NO) and endothelin (ET) were measured 1 h later after I/R. 24 h after I/R hearts were harvested to observe pathological and ultrastructural changes. Immunohistochemistry and western blotting was used to test CD40 expression in myocardial tissue. Area of myocardial infarction were tested, arrhythmia rate during I/R was recorded. RESULTS: Plasm concentration of creatine kinase (CK), CK-MB, hsCRP, NO, MDA and ET were decreased in group C, D compared with group B. Plasm concentration of T-SOD and GSH-Px was increased significantly in group C, D compared with group B. Compared with group B, pathological and ultrastructural changes in group C, D were slightly. Myocardial infarction area and arrhythmia rate were lower in group C, D compare with group B. CONCLUSIONS: Rosiglitazone can protect myocardium from I/R injury by enhancing T-SOD and GSH-Px concentration, inhibit inflammatory reaction, improve endothelial function, reduce oxidative stress and calcium overload.

Combined antihypertensive effect of luteolin and buddleoside enriched extracts in spontaneously hypertensive rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Flos Chrysanthemi is used in a variety of diseases in traditional Chinese medicine including hypertension, and the total flavonoids (rich in luteolin (LUT) and buddleoside (BUD)) of Flos Chrysanthemi is known to modulate vascular functions and reduce the blood pressure. However, the active flavonoids and their synergistic effects on anti-hypertension are still unclear. To investigate the combined anti-hypertension effects of LUT and BUD enriched extracts on spontaneously hypertensive rats (SHR), as well as the anti-hypertensive mechanism of LUT&BUD mixture. MATERIALS AND METHODS: CODA Mouse & Rat Tail-Cuff Blood Pressure System was used to measure the systolic blood pressure (SBP) and diastolic blood pressure (DBP) of SHR after treated with extracts contains with LUT and/or BUD. The expressions of Ang II, PRA, ALD, ET, PGI2 and TXB2 were investigated by ELASA. Serum NO concentration was measured by the method of Nitric acid reductase. RESULTS: A single administration of LUT, BUD, or LUT:BUD=1:1 significantly reduced SBP by about 3.35 mmHg, 4.39 mmHg and 15.42 mmHg, respectively. Chronic administration of LBM (at 60 mg/kg; p.o. for 30 days) reduced both SBP and DBP by 4.04% and 5.24% of the vehicle group, respectively. Oral administration of LBM at 60 mg/kg inhibited the serum levels of ANG, ALD and ET, but increased serum NO concentration. CONCLUSION: This study shows the synergistic anti-hypertension effects of LUT and BUD in SHR. The effects of LBM on blood pressure are associated with RAAS and endothelial system. Thus, our experiments suggest that the combination of luteolin and buddleoside from Flos Chrysanthemi are potentially useful for the therapeutic treatments for hypertension.

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.

Electroacupuncture reduces hemiplegia following acute middle cerebral artery infarction with alteration of serum NSE, S-100B and endothelin.

Acupuncture may help motor recovery in chronic stroke survivors, but it is unclear whether it is useful for acute or subacute stroke patients. This study aimed to assess the effiency of electroacupuncture on hemiplegic patients caused by acute first-ever middle cerebral artery infarction. Ninety-eight patients with hemiplegia after first-ever middle cerebral artery infarction were divided into the observation group and the control group. Electroacupuncture was applied once daily for three weeks seven days after symptom onset. The motor functions of the limbs and the activities of daily living (ADL) were evaluated by Fugl-Meyer assessment (FMA) and Barthel index (BI). Serum neuron-specific enolase (NSE), soluble protein-100B (S-100B) and endothelin (ET) were quantified before and after treatment.After treatment, the FMA and BI scores were improved in comparison to before treatment scores in the same group (P<0.01 or P<0.05), with a more significant improvement in the observation group (with electroacupuncture) than in the control group (P<0.01). After treatments, the amounts of serum NSE, S-100B and ET in the observation group were significantly decreased when compared with those of the control group (P<0.01 or P<0.05). No adverse reactions occurred during electroacupuncture. This study showed that motor functions of the limbs and the activities of daily living in hemiplegic patients caused by acute cerebral infarction were improved significantly after treatment with electroacupuncture and this improvement was associated with reduced serum levels of NSE, S-100B and ET.

Effect of rosiglitazone on rabbit model of myocardial ischemia-reperfusion injury.

OBJECTIVE: To explore mechanism and protective effect of rosiglitazone on myocardial ischemia reperfusion (I/R) injury. METHODS: A total of 48 male Japanese white big-ear rabbits were randomly divided into control group (A), I/R group (B), low dose of rosiglitazone group (C), high dose of rosiglitazone group (D). Plasma concentration of and also reduced the concentration of plasma serum creatine kinase (CK), CK-MB, high-sensitivity C-reactive protein (hsCRP), ultra-superoxide dismutase (SOD), malondialdehyde (MDA), lactic acid glutathione skin peroxidase (GSH-PX), nitric oxide (NO) and endothelin (ET) were measured 1 h later after I/R. Twenty-four hours after I/R the hearts were harvested for pathological and ultrastructural analysis. Area of myocardial infarction were tested. RESULTS: Plasma concentration of CK, CK-MB, hsCRP, NO, MDA and ET were decreased in C, D group compared with group B. Plasma concentration of T-SOD and GSH-Px were increased significantly in C, D group compared with group B. Compared with group B, pathological and ultrastructural changes in C and D group were slightly. There was significant difference in myocardial infarction area between group C, D and group B (P<0.05). Myocardial infarction area and arrhythmia rate were lower in group C, D compare with group B. CONCLUSIONS: Rosiglitazone may protect myocardium from I/R injury by enhancing T-SOD and GSH-Px concentration, inhibit inflammatory reaction, and improve endothelial function.

[Effects of di'ao xinxuekang soft capsule on lipid peroxidation and the endothelial function in patients with coronary heart disease].

OBJECTIVE: To observe the effects of Di' ao Xinxuekang Soft Capsule (DK) on the plasma levels of superoxide dismutase (SOD), malondialdehyde (MDA), nitric oxide (NO), and endothelin (ET) in patients with coronary heart disease (CHD), and to study its underlying mechanisms. METHODS: Totally 100 patients with CHD confirmed by coronary angiography were randomly assigned to two groups, the control group (60 cases) and the DK treatment group (40 cases). Patients in the control group received conventional therapy, while those in the DK treatment group received DK additionally. The therapeutic course for all was 3 months. The plasma levels of SOD, MDA, ET, and NO were determined pre-treatment, 4, 8, and 12 weeks after treatment. RESULTS: Compared with before treatment, the serum levels of SOD and NO increased and the levels of MDA and ET decreased at each time point. Besides, better effects were obtained in the DK treatment group (P < 0.05). CONCLUSION: DK possibly played a role in inhibiting lipid peroxidation and improving the endothelial dysfunction.

Effect of the flavonoid fraction of Lithocarpus polystachyus Rehd. on spontaneously hypertensive and normotensive rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Lilhocarpus polystachys Rehd. (Sweet Tea, ST) is a folk herbal medicine that has been traditionally used as a natural remedy for hypertension in China, whose mechanism remains unveiled. Flavonoid fraction is considered as the major active components in ST. This study aimed to provide experimental evidence for the anti-hypertension activity of flavonoid fraction of ST (ST-F) and investigate the underlying mechanism. The effect of ST-F on the blood pressure of normotensive rats was also to be determined. MATERIALS AND METHODS: Spontaneously hypertensive rats (SHRs) were treated with ST-F daily for 10 weeks. Blood pressure of SHRs was measured before and biweekly during ST-F treatment. Subsequently, animals were sacrificed either immediately at the end of treatment or 2 weeks after ST-F treatment discontinuance. The activities of plasma rennin (PRA), angiotensin II (Ang-I), endothelin (ET), nitric oxide (NO), superoxide dismutase (SOD) and malondialdehyde (MDA) were measured as well as skin microcirculatory flux. In normotensive rats, blood pressure was determined after six months' treatment of ST-F. RESULTS: ST-F treatment significantly reduced the blood pressure of SHRs along with decreasing plasma levels of PRA and Ang II. ST-F did not show obvious effects on plasma levels of ET, NO or SOD, but it significantly decreased the plasma level of MDA and improved skin microcirculatory flux. Compared to the anti-hypertensive drug enalapril, ST-F showed a modest effect on lowering blood pressure of SHRs without obvious withdrawal reactions. But long-term intake of ST-F did not change the blood pressure in normotensive rats. CONCLUSION: ST-F had an antihypertensive effect on SHRs. The underlying mechanism could be related to modulation on the rennin-angiotensin-aldosterone system (RAAS) and antioxidation system, as well as regulation of skin microcirculation. Compared to its anti-hypertensive effect on SHRs, ST-F did not cause hypotension in normotensive rats. The results indicated that ST-F could potentially be used as natural drugs or functional foods for preventing hypertension.

Effect of potassium supplementation on renal tubular function, ambulatory blood pressure and pulse wave velocity in healthy humans.

BACKGROUND: Potassium is the main intracellular cation, which contributes to keeping the intracellular membrane potential slightly negative and elicits contraction of smooth, skeletal and cardiac muscle. A change in potassium intake modifies both cardiovascular and renal tubular function. The purpose of the trial was to investigate the effect of dietary potassium supplementation, 100 mmol daily in a randomized, placebo-controlled, crossover trial of healthy participants during two periods of 28 days duration. The participants (N = 21) received a diet that was standardized regarding energy requirement, and sodium and water intake. METHODS: 24-hour ambulatory blood pressure (ABP) and applanation tonometry were used to assess blood pressure, pulse wave velocity (PWV), augmentation index (AIx) and central blood pressure (CBP). Immunoassays were used for measurements of plasma concentrations of vasoactive hormones: renin (PRC), angiotensin II (Ang II), aldosterone (Aldo), atrial natriuretic peptide (ANP), vasopressin (AVP), pro-brain natriuretic peptide (pro-BNP),endothelin (Endo), urinary excretions of aquaporin 2 (AQP2), cyclic AMP (cAMP), and the ß-fraction of the epithelial sodium channel (ENaC(ß)). RESULTS: AQP2 excretion increased during potassium supplementation, and free water clearance fell. The changes in urinary potassium excretion and urinary AQP2 excretion were significantly and positively correlated. Aldo increased. GFR, u-ENaC- ß, PRC, Ang II, ANP, BNP, Endo, blood pressure and AI were not significantly changed by potassium supplementation, whereas PWV increased slightly. CONCLUSIONS: Potassium supplementation changed renal tubular function and increased water absorption in the distal part of the nephron. In spite of an increase in aldosterone in plasma, blood pressure remained unchanged after potassium supplementation.

[Effects of training on plasma content of nitric oxide, endothelin and NO/ET system in rats fed with high methionine diet].

OBJECTIVE: To observe the effects of training on plasma content of NO, ET and NO/ET system in rats fed with high methionine diets. METHODS: Male Wistar rats were randomly divided into normal diet group (CR), high methionine diet group (MR) and high methionine diet plus 90 min swimming group (T+ MR). Rats in MR and T+ MR group were fed with the diet which contained 3%of methionine for eight weeks, but rats in control group were fed with ordinary diet. After breeding for eight weeks homocysteine (Hcy) level, T-NOS, NO and ET were measured. RESULTS: Plasma homocysteine of MR increased twofold as compared with that of CR,whereas plasma NO/ET of MR descended significantly (P < 0.05), suggesting that hyperhomocysteinemia was induced by the high methionine diet, and plasma NO/ET system was out of balance. Plasma homocysteine content of T+ MR obviously descended, plasma T-NOS, NO and NO/ET ascended obviously (P < 0.05) as compared with that of MR, and the above indicators of group T + MR were not different as compared with that of CR (P > 0.05). CONCLUSION: Proper training can descend plasma homocysteine level of rats fed with high methionine diet and better balance between NO and ET to prevent developing of hyperhomocysteinemia.

Ginsenoside Rb3 ameliorates myocardial ischemia-reperfusion injury in rats.

CONTEXT: Panax ginseng C. A. Mey (Araliaceae) has been widely used in clinic for treatment of cardiovascular diseases in China. Ginsenoside Rb3 is the main chemical component of Panax ginseng. OBJECTIVE: The aim of this study was to evaluate the effect of ginsenoside Rb3 on myocardial ischemia-reperfusion injury in rats. METHODS: Sprague--Dawley rats were orally treated with Rb3 (5, 10 or 20 mg/kg) daily for 3 days followed by subjecting to left anterior descending coronary artery ligation for 30 min and reperfusion for 24 h. RESULTS: This study showed that ginsenoside Rb3 treatment resulted in a reduction in myocardial infarct size. Ginsenoside Rb3 significantly attenuated the changes of creatine kinase activity and lactate dehydrogenase activity. The cardioprotective effect of ginsenoside Rb3 was further confirmed by histopathological examination. Ginsenoside Rb3 alleviated the increase of malondialdehyde content and the decrease of superoxide dismutase activity in left ventricle. Treatment with ginsenoside Rb3 also decreased plasma endothelin and angiotensin II levels. CONCLUSION: These findings suggested that ginsenoside Rb3 possesses the effect against myocardial IR injury and the underlying mechanism is related to its antioxidant activity and microcirculatory improvement.

Injectable caltrop fruit saponin protects against ischemia-reperfusion injury in rat brain.

The present study aimed to investigate the protective effects of injectable caltrop fruit saponin preparation (ICFSP) on ischemia-reperfusion injury in rat brain. Rats were injected with ICFSP and then subjected to cerebral ischemia-reperfusion injury induced by middle cerebral artery occlusion. Then the neurological deficit score was evaluated by Bederson's method. The infarct size was assessed by TTC staining. The content of malondialdehyde (MDA) and nitric oxide (NO), and the activity of superoxide dismutase (SOD) in rat cerebrum were measured with kits, and the content of 6 K prostaglandin F1α (6-K-PGF 1α), thromboxane B2 (TXB2) and endothelin (ET) in blood plasma was measured by radioimmunoassay. The results demonstrated that ICFSP led to a decrease in infarct size (p < 0.01), neurological deficit score (p < 0.05) and plasma content of TXB2 and ET (p < 0.05), and an increase of the plasma level of 6-K-PGF 1α (p < 0.05) and SOD activity in cerebrum, where the MDA and NO content were decreased. The treatment improved forelimb function. ICFSP showed a similar potency compared to that of Ligustrazine hydrochloride parenteral solution (LHPS) and nimodipine (Nim). We concluded that ICFSP protects the brain damage caused by ischemia-reperfusion injury in rats, and this may be closely related to the regulation of reactive oxygen species (MDA and SOD activity) and NO levels in the rat cerebrum, as well as vasoactive factors in the plasma (6-K-PGF 1α, TXB2 and ET).

[Effect of acupuncture-assisted anesthesia on stress response during laparoscopic cholecystectomy in aged patients].

OBJECTIVE: To compare the difference between transcutaneous electrical acupoint stimulation (TEAS) assisted general anesthesia and simple general anesthesia on stress response during laparoscopic cholecystectomy (LC) in aged patients. METHODS: Forty patients underwent LC were randomly divided into a TENS assisted general anesthesia group (group T) and a general anesthesia group (group G), 20 cases in each group. After TEAS for 30 min, general anesthesia was applied in group T, and TEAS was continued until LC over. In group G, only routine general anesthesia was given. Mean arterial pressure (MAP), heart rate (HR), saturation of blood oxygen (SpO2), PetCO2, and the contents of plasma endothelin (ET), cortisol (Cor) were measured before anesthesia (T0) and after intubation cannula 5 min (T1), after pneumoperitoneum 5 min (T2) and 15 min (T3), and LC over (T4). The rate of hypotension and hypertension were observed during preoperative period. RESULTS: The hemodynamics indices decreased in group G at T1 than before. The reductions of MAP and HR in group G were larger than those in group T at T1 (P < 0.05). After pneumoperitoneum, the hemodynamics indices and serum ET and Cor have no differences in group T as compared with before (all P > 0.05), but they were all increased more significantly in group G than before, and with significant differences between group G and group T at each time point (P < 0.05, P < 0.01). CONCLUSION: Acupuncture-assisted anesthesia profit to maintain the hemodynamic stable and reduce the stress response during LC in aged patients.