Mechanism of Shengmaisan Regulating Cardiac Remodeling of Arrhythmias with Deficiency of Qi and Yin / 中国实验方剂学杂志

Arrhythmia is an important disease among cardiovascular diseases. Malignant arrhythmias often occur clinically and are induced by abnormal ion channels， electrical activity disorders， myocardial fibrosis， inflammation， dysfunctional mitochondrial biogenesis， mitochondrial calcium overload， out-of-balance energy metabolism， oxidative stress， sympathetic hyperactivity， and other pathological cardiac remodeling， and they are the main causes of sudden cardiac death. In traditional Chinese medicine， arrhythmias are considered to be palpitations， which are commonly caused by deficiency of Qi and Yin. It is often manifested as a deficiency of the spleen and stomach， resulting in malfunction of the Qi mechanism， followed by a particularly severe decline in cardiac function. Shengmaisan is a representative formula for nourishing Qi and Yin， consisting of Ginseng Radix et Rhizoma， Ophiopogonis Radix， and Schisandrae Chinensis Fructus. In recent years， clinical studies have shown that Shengmaisan and its additions and subtractions are commonly used in the treatment of arrhythmias. In this article， the mechanisms of the active ingredients of Shengmaisan in the electrophysiology， biochemistry， structure， autonomic nervous system， and subcellular fraction of the heart are reviewed， and the multi-target， multi-system， and integrality of Shengmaisan in the treatment of arrhythmias of Qi and Yin deficiency are described. In addition， energy metabolism disorder is tightly juxtaposed with Qi and Yin deficiency syndrome. Mitochondria， as the center of myocardial energy metabolism， play a paramount role in cardiac remodeling， indicating that Shengmaisan will be a salient part of future research to ameliorate cardiac pathologic remodeling through energy metabolism of mitochondria， so as to provide a theoretical basis for the clinical treatment of these arrhythmias.

Effort of Xiaoyu-Jiangzhi capsules on carotid artery atherosclerosis in Apolipoprotein E gene knockout mice / 国际中医中药杂志

Objective:To investigate the effects of Xiaoyu-Jiangzhi capsules on blood lipid, carotid artery atherosclerosis (CAA) and plaque in apolipoprotein E knockout (ApoE -/-) mice. Methods:The ApoE -/- mice were fed with high-fat food to establish carotid atherosclerosis model. The ApoE -/- mice were randomly by weight divided into model group, Atorvastatin group, low- and high-dose Xiaoyu-Jiangzhi capsules group. The C57BL/6cnc mice were used as control group and fed with normal diet. The Atorvastatin group was given atorvastatin suspension 1.3 mg/kg, low and high dose groups were given Xiaoyu-Jiangzhi capsule suspension 325 and 975 mg/kg, and the control group and model group were given equal volume of distilled water. The mice were gavaged with 0.1 ml/10 g body weight, once a day, and the weight of mice was recorded weekly. After 12 weeks of continuous intragastric administration, the blood lipid and liver /body weight index of the mice were measured. Carotid arteries were sliced to conduct oil red O staining and VG staining for the pathological analysis. Results:After 12 weeks of drug administration, the weight of mice in the high-dose group was significantly lower than the model group. The level of TC (25.92 ± 4.21 mmol/L vs. 30.39 ± 4.67 mmol/L) and LDL-C (7.97 ± 2.14 mmol/L vs. 10.26 ± 1.97 mmol/L) in the high-dose group significantly decreased ( P<0.05), the level of HDL-C in the low and high-dose group significantly increased ( P<0.05). The pathological results showed that after 12 weeks of administration, the carotid artery lipid deposition blockage rate in the Atorvastatin group and the high dose group were significantly smaller than the model group( P<0.05), and no vascular plaque has been formed. Conclusion:The Xiaoyu-Jiangzhi capsules could reduce LDL-C, increase HDL-C levels, reduce the constriction of arterial stenosis and slow down the formation process of carotid plaque.

Determination of active ingredients and prediction of targetin Sanhua Decoction for cerebral ischemia based on HPLC and network pharmacology methods / 国际中医中药杂志

Objective:To determinate the active ingredients and predicte action targets in Sanhua Decoction for treating cerebral ischemia based on HPLC and network pharmacology methods. Methods:The HPLC analysis was performed on HC-C18 (250 mm × 4.6 mm, 5 μm) with the mobile phase of methanolacetonitrile-0.05% phosphoric acid with gradient elution at the flow rate of 1.0 ml/min and 0.8 ml/min. The detection wavelength was set at 254 nm, the column temperature was at 30 ℃, and the injection volume was 10 μl. TCMIP v2.0 platform was used to search the action targets of rhein, emodin, chrysophanol, hesperidin, magnolol and notopterygiol. We used Cerebral ischemia as a keyword searching the databases such as Genecards, OMIM, TTD, and Disgenet to screen six potential targets for the treatment of cerebral ischemia by active ingredients, construct a protein interaction (PPI) network and a disease-component-target-pathway integration network.Results:The literature search determined that rhein, emodin, chrysophanol, hesperidin, magnolol and qianhuol were the index components for the determination of Sanhua Decoction. Their linear ranges were 0.080 4-0.804 0 μg, 0.015 3-0.382 0 μg, 0.041 8-0.626 4 μg, 0.312 6-3.908 0 μg, 0.037 9-0.568 8 μg, 0.045 3-1.359 6 μg, respectively. The correlation coefficient R 2 is greater than 0.999 0. The content ranges of the above six components in seven samples were 0.887-0.971 mg/g, 0.094-0.101 mg/g, 0.110-0.119 mg/g, 1.494-1.669 mg/g, 0.126-0.145 mg/g and 0.153-0.167 mg/g, respectively. Network pharmacology analysis found that the targets of the six components for the treatment of cerebral ischemia may be TNF, TP53, MAPK14, JUN, IL1B, MYC, ESR1, ICAM1, PTGS2, PPARG and so on. Conclusions:A quality control method forthe six active ingredients in Sanhua Decoction treating cerebral ischemia was established. This method is simple and repeatable. The ten potential targets of the six active ingredients in Sanhua Decoction for the treatment of cerebral ischemia have been clarified, laying a foundation for further research on the action mechanism.

Study on the interaction of injection salvia miltiorrhiza dried powder and aspirin in antithrombotic function / 国际中医中药杂志

Objective To investigate the antithrombotic function of traditional medicine salvia and aspirin in the myocardial infarction rats. Methods The myocardial infarction animal model was established by ligating left anterior descending coronary artery. The rats were randomly divided into the model group, the aspirin group, the salvia miltiorrhiza group, and the combination therapy group, with 8 rats in each group. The salvia miltiorrhiza group was injected with Danshen freeze-dried powder 17 mg/kg via tail vein injection, aspirin group was given aspirin 10 mg/kg, the combination group was given aspirin 10 mg/kg with the tail vein injected with Danshen freeze-dried powder 17 mg/kg, and the model group was given an equal volume of normal saline with an equal volume of saline injected into the tail vein. Continuous administration last 10 days, once daily. The blood coagulation, platelet aggregation, thromboxane B2, 6-Keto-F1α and von Willebrand factor were detected and compared. Results Compared with the model group, the maximum platelet aggregation rate(32.55％ ± 9.57 ％, 32.16％ ± 10.76％, 19.74％ ± 6.70％ vs. 58.75％ ± 4.81％) in the rats of the aspirin group, the salvia group and the combined treatment group significantly decreased, and the contents of TXB2 (70.58 ± 9.31 ng/ml, 73.10 ± 11.33 ng/ml, 49.25 ± 5.33 ng/ml vs. 107.86 ± 17.45 ng/ml) decreased (P<0.01). The maximum platelet aggregation rate and contents of TXB2 in the combination group were lower than those in the aspirin group and the salvia group (P<0.01). Compared with the model group, the 6-Keto-PGF1α content (67.64 ± 7.12 ng/ml, 81.72 ± 10.72 ng/ml vs. 57.80 ± 11.19 ng/ml) of the aspirin group and the combined treatment groupwas increased (P<0.05), prothrombin time (13.11 ± 0.67 s, 15.85 ± 0.25 s vs. 10.77 ± 0.46 s) prolonged (P<0.05), vWF (51.31 ± 4.12 ng/ml, 47.72 ± 10.32 ng/ml vs. 128.81 ± 11.14 ng/ml) decreased (P<0.05). The contents of 6-Keto-PGF1α of the combined treatment group was increased compared with aspirin group and salvia group (P<0.05), prothrombin time decreased than aspirin group (P<0.05) and Salvia group and vWF decreased than Salvia group (P<0.05). Conclusions The salvia miltiorrhiza and aspirin combination therapy has synergistic effect on anti-platelet aggregation and anticoagulant effect. The salvia miltiorrhiza and aspirin combination therapy showed small bleeding risk.

Role of Toll-like receptor 4 in non-medullary and medullary cells in lung ischemia-reperfusion injury in mice / 中华麻醉学杂志

Objective To evaluate the role of Toll-like receptor 4 (TLR4) in non-medullary andmedullary cells in lung ischemia-reperfusion (I/R) injury in mice.Methods Ten healthy male TLR4+/+ in non-medullary cells/TLR4+/+ in medullary cells (WT/WT) mice,10 TLR4-/-in non-medullary cells/ TLR4-/-in medullary cells (KO/KO) homozygote mice,10 TLR4+/+ in non-medullary cells/TLR4-/-in medullary cells (WT/KO) mice,and 10 TLR4-/-in non-medullary cells/TLR4+/+ in medullary cells (KO/WT) heterozygote mice,aged 6-8 weeks,weighing 20-25 g,were used in the study.Lung I/R was induced by occlusion of the left hilum for 60 min followed by 240 min of reperfusion in anesthetized mice.Blood samples were obtained from the femoral artery at 240 min of reperfusion for blood gas analysis,and the oxygenation index (PaO2/FiO2) was calculated.The animals were then sacrificed and lung tissues were immediately removed for determination of wet/dry weight ratio,myeloperoxidase activity and contents of tumor necrosis factor-alpha,interleukin-1beta (IL-1β) and IL-6 (by enzyme-linked immunosorbent assay) and for microscopic examination of the pathological changes of lungs which were scored.Results Compared with WT/WT mice,the oxygenation index was significantly increased in sequence,and lung injury scores,wet/dry weight ratio,myeloperoxidase activity and contents of tumor necrosis factor-alpha,IL-1β and IL-6 were decreased in sequence in WT/KO,KO/WT and KO/KO mice (P＜0.05).Conclusion TLR4 in non-medullary cells plays a rnore important role in lung I/R injury than that in medullary cells of mice.

Experimental study on anti-inflammatory effects ofHuamoyan granules / 国际中医中药杂志

Objective The purpose of this study was to investigate the anti-inflammatory effects on acute and chronic inflammation ofHuamoyan Granules(HMYG).Methods KM mice and SD rats were randomly divided into model group, ibuprofen group and HMYG high, middle and low three dosages groups. The Ibuprofen group was administrated drug by gavage, mice 0.13 g/kg and rats 0.093 g/kg. The HMYG groups were administrated orally, mice 12, 6 and 3g/kg, rats 4, 4.2 and 2.1 g/kg. The model group was given the same volume distilled water, once a day, 3 or 10 continuous days. The increased permeability of mice abdominal capillary was induced by acetic acid, edema of rat hind paw was induced by albumen and carrageenin, which both were adopted to observe the acute anti-inflammatory effects; and cotton pellet granuloma was to observe the chronic anti- inflammation effects of HMYG.Results Compared with the model group, the ibuprofen group, the HMYG high and middle group showed anti-inflammatory actions of mice induced by acetic acid (0.185 ± 0.046, 0.177 ± 0.055, 0.190 ± 0.052vs. 0.246 ± 0.050,P<0.05 orP<0.01); after 0.5, 1, 2, 4 and 6 hrs inflammation, HMYG high dosage group had significant inhibition for the edema of rats hind paw induced byalbumen model, the inhibitory rate was 22.46%, 19.20% and 24.32%, 33.75%, 24.19%; 4 and 6 hrs after inflammation, HMYG high dosage group could reduce rats paw edema induced by carrageenin, the inhibitory rate was 32.05%, 30.56% and 19.23%, 20.83%.Conclusion HMYG has evident anti-inflammatory effects on acute inflammation.

Effects of aconitine, mesaconitine and hypaconitine on calcium release in isolated adult rat cardiac myocytes / 国际中医中药杂志

ObjectiveTo investigate the effects of aconitine, mesaconitine and hypaconitine on calcium release in isolated adult rat cardiac myocytes.MethodsThe left ventricular cardiac myocytes isolated from adult Sprague-Dawley rats were perfused withacnitine, mesaconitine and hypaconitine at 0.3 μmol/L, 1μmol/L, 3 μmol/L for 12 min. The spontaneous calcium release (SCR) rate, the end-diastolic[Ca2+](F0) and the calcium transient amplitude (ΔF) were detected 4 min, 8 min and 12 min after the perfusion. 12 min after the perfusion with acnitine, mesaconitine and hypaconitine at 0.3 μmol/L, the changes of systolic dynamics and calcium transient were detected for the positive inotropic effect. Results Any of aconitine, mesaconitine and hypaconitine induced SCR, mesconitine-induced SCR rate was highest at low concentration (0.3 μmol/L), and aconitine-induced SCR rate highest at high concentration (3 μmol/L). Compared with the control, 12 min after the perfusion with acnitine, mesaconitine and hypaconitine at 3 μmol/L elevated F0 (1.459 ± 0.379, 1.585 ± 0.493, 1.213 ± 0.254vs.1.079 ± 0.108, allP<0.05) and ΔF(1.615 ± 0.455, 2.210 ± 0.756, 1.528 ± 0.422vs. 1.036 ± 0.125, allP<0.05), mesaconitine with ΔF higher than aconitine and hypaconitine. At low concentration (0.3 μmol/L), compared with control, aconitine, mesaconitine and hypaconitine increased ΔF (0.409 ± 0.127, 0.423 ± 0.107, 0.414 ± 0.118vs.0.260 ± 0.065;P<0.05 orP<0.01) and contraction amplitudes (5.464% ± 2.239%, 7.449% ± 2.548%, 5.524% ± 1.645%vs.3.428% ± 0.911%;P<0.05 orP<0.01), prolonged the time to peak of calcium transient (0.041 ± 0.016 s, 0.039 ± 0.009 s, 0.038 ± 0.011 svs.0.032 ± 0.007 s;P<0.05 or P<0.01); compared with aconitine, mesaconitine and hypaconitine decreased calcium transient time constant (0.301 ± 0.054 s, 0.324 ± 0.064 svs.0.361 ± 0.076 s;P<0.05 orP<0.01) and diastolic t50 (0.124 ± 0.035 s, 0.126 ± 0.040 svs.0.157 ± 0.056 s;P<0.05 orP<0.01).ConclusionsAconitine, mesaconitine and hypaconitine reveal the positive inotropic effects couple with the toxic effects. Increased[Ca2+]in cardiac myocytes is the key factor for the positive inotropic effects, but also the risk factor for SCR.

Comparison of analgesic effect of Huamoyan Keli between two strains of mice / 国际中医中药杂志

Objective To compare the analgesic effect ofHuamoyan Keli(HMYKL) between Kunming mice and BALB/c mice.Methods Eighty Kunming mice and eighty BALB/c mice were randomly divided into five groups, respectively: a control group, a ibuprofen group, a HMYKL high-dose group(13.98 g crude dru g/kg), HMYKL middle-dose group(6.99 g crude drug/kg)and a HMYKL low-dose group(3.50 g crude dru g/kg). There were 16 mice in each group with 8 male mice and 8 female mice. Drugs were administered intragastrically daily for 5 days. After 1 h of drug treatment on day 4, the latency of tail-flick response was evaluated using illuminated pain measurement instrument. After the last drug treatment, pain model was established by i.p. acetic acid, writhing latency and writhing times were recorded to evaluate the analgesic effect of HMYKL.Results In tail-flick test, there was no statistical difference among male and female Kunming mice in the HMYKL groups. Among male BALB/c mice, the latency in HMYKL middle-dose group was significantly longer than that in the control group(4.84±1.16 minvs. 3.93±0.76 min,P<0.05). In writhing test, compared with control group(19.06±6.34), the writhing times among BALB/c mice were decreased in HMYKL high-dose group(8.56±6.19), HMYKL middle-dose group(5.73±3.17), HMYKL low-dose group(6.88±4.59)(allP<0.01).Conclusion All dose groups of HMYKL showed good analgesic effect on the pain induced by chemical stimulation and there was no sex difference. Kunming mice were not suitable for the evaluation of the analgesic pharmacodynamics because of their large individual difference. On contrast, BALB/c mice which had less individual difference could be used to produce the model of pain.

Protective effects of xuefu zhuyu decoction on myocardium ischemia reperfusion injury in rats / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the protective effects of Xuefu Zhuyu decoction on myocardium ischemia reperfusion injury in rats.</p><p><b>METHOD</b>36 SD rats were divided into 3 groups randomly, sham-operated group, model group, Xuefu Zhuyu decoction group. The model of MI/RI of the myocardium was reproduced by ligation of left descending artery for 30 min followed by releasing the ligation for 2 hours in rats. Serum contents of LDH-L, CK were measured, the levels of serum IL-1beta, IL-6 and IL-10 were measured and myocardial ultrastructure at the ischemia region was observed under the transmission electron microscope after myocardial reperfusion injury.</p><p><b>RESULT</b>Compared with model group, IL-1beta, IL-6 and IL-10 levels were lower, myocardial ultrastructural changes were improved in Xuefu Zhuyu decoction group (P < 0.01), however, serum contents of LDH-L and CK no significant difference were found among the model group and Xuefu Zhuyu decoction group.</p><p><b>CONCLUSION</b>Xuefu Zhuyu decoction can protect myocardium from MI/RI, the mechanism of action was related to inhibiting inflammatory reaction and reducing arrhythmia and the injury of the myocardial ultrastructure.</p>

Contrast Observation on Protective and Therapeutic Effects of Different Therapies and Formulas on Myocardial Ischemia Reperfusion Injury in Rats / 国际中医中药杂志

Objective To investigate the protective effects of different Chinese medical treatments on myocardial ischemia-reperfusion injury in rats. Methods 60 SD rats were divided into 5 groups randomly: a sham-operated group, a model group, a removing phlegm and enlarging chest group, an activating blood and dissolving stasis group, and a treating both phlegm and blood stasis group. The model of MI/RI of the myocardium was reproduced by ligation of left descending artery for 30min followed by releasing the ligation for 2 hours in rats. Serum contents of LDH-L, CK were measured , TNF-αand ICAM-1 expressions in myocardium were determined with immunohistochemistry and myocardial ultrastructure at the ischemia region was observed with the transmission electron microscope after myocardial reperfusion injury. Results Compared with the model group, LDH-LXK and TNF-αICAM-1 levels were lower, myocardial ultrastructural changes were improved in all the other four groups treated by different Chinese medicine (P<0.01 or P<0.05), especially in the group treating both phlegm and stasis. Conclusion The removing phlegm and enlarging chest method, activating blood and dissolving stasis method, treating both phlegm and blood stasis method can protect myocardium from M1/R1, especially the method of treating both phlegm and blood stasis.

Effect Observation and Mechanism Exploration of Huiyang Shengji Ointment in Treating Chronic Refractory Skin Ulcer / 中国中医药信息杂志

Objective To research the curative effect of the chronic refractory skin ulcer,which belong to yang deficiency of both spleen and kidney type with the treatment of Huiyang Shengji ointment,and discuss the mechanism at cell and molecular level.Methods According to the diagnostic criteria,102 patients were divided into the treatment group(treated with topical Huiyang Shengji ointment) and the control group(treated with topical chlorhexidine).The effects were summarized six weeks later.The marginal tissue of the patients with the chronic skin ulcer was taken to analyze collagen Ⅰ/Ⅲ with the software and the expression of cytokine FGF-2,VEGF,Fn were observed during the wound heal.Results The effective rate was 50% in the treatment group,the control group was 33.33%,with statistical differences.Huiyang Shengji ointment can change the status of the chronic wound,promote growth of new blood vessels and improve the collagen synthesis,especially collagenⅠ.The expression of the FGF-2 and VEGF in the marginal tissue of the chronic skin ulcer showed a rising trend.Conclusions Huiyang Shengji ointment can accelerate the wound heal of chronic refractory skin ulcer.One of the mechanisms is related to promoting growth of new blood vessels and improving the collagen synthesis.