Network meta-analysis of five Chinese patent medicines in the treatment of coronary microvascular disease / 国际中医中药杂志

Objective:To evaluate the clinical efficacy rate, vascular endothelial relaxation factor NO and safety of five different Chinese patent medicines combined with western medicine in the treatment of coronary microvascular disease (CMVD).Methods:Randomized controlled trials (RCTs) of Shexiang Baoxin Pills, Tongxinluo Capsules, Compound Danshen Dripping Pills, Yindan Xinnaotong Soft Capsules, and Xinkeshu Tablets combined with conventional western medicine therapy in the treatment of CMVD were retrieved from China National Knowledge Infrastructure (CNKI), China Academic Journal Database (Wanfang Data), Chinese Science and Technology Journal Database (Chongqing VIP), China Biomedical Literature Service System (SinoMed), PubMed, Cochrance Library and Embase databases from the establishment of the database to June 2022. The literature was imported and screened by EndNote software, and the risk quality of literature bias was evaluated by Revman 5.4 software. StataSE16 (64-bit) software was used for reticular meta analysis to compare the differences in clinical efficacy and drug safety of five proprietary Chinese medicines combined with western medicine.Results:A total of 24 RCT studies were included, 24 of which were double-arm studies, and five kinds of proprietary Chinese medicine combined with western medicine were compared. The results of reticular meta analysis: in terms of improving the clinical effective rate, the order of the five proprietary Chinese medicine combination groups was as follows: Yindan Xinnaotong Soft Capsules group > Shexiang Baoxin Pills group > Tongxinluo Capsules group > Xinkeshu Tablets group > Compound Danshen Dripping Pills group. In terms of regulating vasodilation factor NO, the order of the four proprietary Chinese medicine combination groups is as follows: Yindan Xinnaotong Soft Capsules group > Compound Danshen Dripping Pills group > Tongxinluo Capsules group > Shexiang Baoxin Pills group. In terms of safety, there were 3 reports of adverse reactions in the research literature of the five proprietary Chinese medicines.Conclusions:The clinical efficacy rate of five kinds of proprietary Chinese medicine combined with western medicine routine regimen is better than that of western medicine routine regimen alone, and the combination group of four kinds of proprietary Chinese medicine is superior to western medicine in regulating vasodilation factor NO, and Yindan Xinnaotong Soft Capsules group is superior in clinical efficacy rate and regulation of vasodilation factor NO. However, the quality and samples of this study are different, and the comparison of the curative effect of the combined group of proprietary Chinese medicine still needs a large sample and high-quality RCT study to demonstrate.

Theoretical Exploration of Luobing Theory Guides Study on Alzheimer's Disease Based on Neurovascular Protection / 中国实验方剂学杂志

Based on the correlation between Qi and blood in traditional Chinese medicine， the collateral disease theory puts forward that the Qi-collateral go hand in hand with the vessel-collateral of the brain， and to be as close as lips to teeth in structure and function， which is an important basis for the function of brain governing mind. And this theory proposes that deficiency/stagnancy of collateral-Qi， stagnation of collaterals and loss of consciousness are the main pathogenesis of Alzheimer's disease（AD）， which is different from the research strategy of modern medicine focusing on neurons. It is suggested that it is necessary to treat AD from two aspects， including neuronal protection（elimination of pathological products such as β-amyloid and phosphorylated tau protein） and cerebral microvascular protection（protection of cerebral microvascular structure and function， promotion of therapeutic angiogenesis and increase of cerebral blood flow. Tongxinluo capsules is a representative drug for dredging collaterals developed under the guidance of the therapeutic principle of collaterals need circulation， it can protect microvessels and play a neuroprotective role mediated by vascular protection. Clinical studies have confirmed that Tongxinluo capsules can effectively treat AD， vascular dementia and cognitive impairment related diseases， which can provide new ideas and effective treatment ways to prevent and treat AD from neurovascular protection in a comprehensive manner.

Protective Effects and Potential Mechanism of Tongxinluo on Mice with Thromboangiitis Obliterans Induced by Sodium Laurate / 中国结合医学杂志

OBJECTIVE@#To investigate the effects of Tongxinluo (TXL) on thromboangiitis obliterans (TAO) and the underlying mechanisms.@*METHODS@#Ninety male C57/BL6J mice were randomly divided into 6 groups according to a random number table: the sham group, TAO model group, Compound Danshen Tablet (CDT) group, and the high-, medium-, and low-dose TXL groups. All mice except the sham group were injected with sodium laurate (0.1 mL, 5 mg/mL) in the femoral artery to establish TAO mouse model. After modeling, mice in the sham and TAO model groups were intragastrically administered 0.5% (w/v) sodium carboxymethylcellulose, mice in the CDT group were intragastrically administered 0.52 g/kg CDT, and mice in the TXL-H, TXL-M, and TXL-L groups were intragastrically administered 1.5, 0.75, and 0.38 g/kg TXL, respectively. After 4 weeks of gavage, the recovery of blood flow in the lower limbs of mice was detected by Laser Doppler Imaging. The pathological changes and thrombosis of the femoral artery were observed by morphological examination. The expressions of tumor necrosis factor α (TNF-α) and inducible nitric oxide synthase (iNOS) in the femoral artery wall were detected by HE staining. Levels of thromboxane B2 (TXB2), 6-keto-prostaglandin F1α (6-keto-PGF1α), endothelin-1 (ET-1), interleukin (IL)-1β and IL-6 were measured using enzyme-linked immunosorbent assay (ELISA). Levels of activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT) and fibrinogen (FIB) were detected by a fully automated biochemical analyzer.@*RESULTS@#TXL promoted the restoration of blood flow in the lower limbs, reduced the area of thrombosis in the femoral artery, and alleviated the pathological changes in the femoral artery wall. Moreover, the levels of TXB2, ET-1, IL-6, IL-1β, TNF-α and iNOS were significantly lower in the TXL groups compared with the model group (P<0.05 or P<0.01), while the level of 6-keto-PGF1α was significantly higher (P<0.01). In addition, APTT, PT, and TT were significantly prolonged in TXL groups compared with the model group (P<0.05 or P<0.01), and FIB levels were significantly decreased compared with the model group (P<0.01).@*CONCLUSIONS@#TXL had a protective effect on TAO mice, and the mechanism may involve inhibition of thrombosis and inflammatory responses. TXL may be a potential drug for the treatment of TAO.

Intervention effect of Tongxinluo capsule on renal fibrosis in diabetic nephropathy rats / 中国药房

OBJECTIVE To explore the intervention effect and related mechanism of Tongxinluo capsule on renal fibrosis in rats with diabetic nephropathy （DN）. METHODS Eight rats were selected as control group （ordinary feed）， the remaining rats were given high-glucose and high-fat diet combined with ip injection of streptozotocin （35 mg/kg） to induce DN model. Model rats were randomly divided into model group （purified water）， irbesartan group （positive control， 14.12 mg/kg） and Tongxinluo capsule group （0.3 g/kg）， including 12 rats in the model group and 11 rats for each of the other two groups. All groups were given relevant medicine or water intragastrically， once a day， for 16 consecutive weeks. After the last medication， fasting blood glucose and 24 h urinary total protein （24 h UTP） were detected. Pathological changes in renal cortex of rats in each group were observed. Serum levels of tissue-type plasminogen activator （PA） and plasminogen activator inhibitor 1 （PAI-1） were measured. mRNA expressions of transforming growth factor-β（1 TGF-β1）， type Ⅳ collagen（COL-Ⅳ）， Wnt4 and β-catenin in renal cortex of rats were detected. The protein depositions or expressions of TGF-β1， COL-Ⅳ， focal adhesion kinase （FAK）， integrin-linked kinase （ILK）， E-cadherin， PA， PAI-1， Wnt4 and β-catenin in renal cortex of rats were observed or determined. RESULTS Compared with model group， 24 h UTP of rats in Tongxinluo capsule group were all significantly reduced （P＜0.05）； pathological damage and fibrosis of renal cortex were relieved； the expression of PA in serum and renal cortex was significantly increased， while PAI-1 level was significantly reduced （P＜0.05）； the depositions of COL-Ⅳ and TGF-β1 in renal cortex were all reduced， and corresponding mRNA expression was decreased significantly （P＜0.05）； the depositions of ILK and FAK were decreased， while the deposition of E-cadherin was increased； protein and mRNA expressions of Wnt4 and β-catenin were significantly reduced （P＜0.05）. CONCLUSIONS Tongxinluo capsule can relieve pathological damage to renal tissue and renal fibrosis of DN model rats， and reduce extracellular matrix deposition. The mechanism may be related to regulation of fibrinolytic system activity， the decrease of ILK and FAK expression， and inhibition of Wnt/β-catenin signaling pathway.

Effect of Tongxinluo capsule on improvement of cardiac function and expression of myocardial enzyme spectrum in patients with coronary heart disease after percutaneous coronary intervention / 中国医师进修杂志

Objective:To investigate the effects of Tongxinluo capsule on the improvement of cardiac function and the expression of myocardial enzyme spectrum in patients with coronary heart disease after percutaneous coronary intervention (PCI).Methods:One hundred patients with coronary heart disease after PCI who received treatment in Hebei Xianghe County People′s Hospitalfrom April 2018 to April 2020 were enrolled and randomly divided into the observation group and the control group. The control group was given conventional treatment, while the observation group was treated with Tongxinluo capsule on the basis of the control group. Patients in both groups were treated for 3 months. The normal clinical remission after treatment was observed in the two groups. The improvement of cardiac function index left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left ventricular ejection fraction (LVEF) and myocardial enzyme index aspartate aminotransferase (AST), creatine kinase (CK), creatine kinase isoenzyme - MB (CK - MB), lactate dehydrogenase (LDH), troponin T (TnT) were compared between the two groups before and after the treatment.Results:After treated for 3 months, the total effective rate in the observation group was higher than that in the control group: 92.0%(46/50) vs. 76.0%(38/50), the difference was statistically significant ( χ2 = 4.76, P<0.05). After treated for 3 months, the levels of LVEDV and LVESV in two groups were decreased, and the level of LVEF in two groups was increased, and the levels of LVEDV and LVESV in the observation group were lower than those in the control group: (153.39 ± 8.35) ml/m 2 vs. (155.57 ± 9.32) ml/m 2, (103.49 ± 9.25) ml/m 2 vs. (109.65 ± 10.46) ml/m 2; the levels of LVEF in the observation group was higher than that in the control group: (58.14 ± 7.41)% vs. (54.59 ± 6.92)%, the differences were statistically significant ( P<0.05). After treated for 3 months, the levels of AST, CK, CK-MB, LDH, TnT in two groups were decreased, and the levels of above index in the observation group were lower than those in the control group: (38.14 ± 7.28) U/L vs. (45.04 ± 8.12) U/L, (637.15 ± 75.25) U/L vs. (756.24 ± 85.24) U/L, (553.28 ± 53.14) U/L vs. (632.17 ± 62.81) U/L, (162.43 ± 15.41) U/L vs. (181.74 ± 19.25) U/L, (0.32 ± 0.15) μg/L vs. (0.39 ± 0.11) μg/L, the differences were statistically significant ( P<0.05). Conclusions:The application of Tongxinluo capsule in patients with coronary heart disease after PCI can effectively alleviate clinical symptoms, improve cardiac function, and regulate the enzyme activity of the body.

Collaterals Doctrine Guided Investigation into Traditional Chinese Medicine Pathogenesis and Clinical Treatment of Myocardial Fibrosis Following Acute Myocardial Infarction / 中国实验方剂学杂志

Interventional or thrombolytic therapy for acute myocardial infarction （AMI） has the effect of opening occluded coronary arteries. However， due to no myocardial regurgitation， ischemia/reperfusion injury and microvascular structure and function destruction， leading to myocardial fibrosis following AMI， ventricular remodeling， and even cardiac failure may occur. Collaterals doctrine is used to guide the investigation into traditional Chinese medicine pathogenesis and clinical treatment of myocardial fibrosis following AMI. Consequently， it proposes the pathogenesis characteristic of "Qi deficiency and blood stasis， collaterals obstruction" and medication principle of "dispersing and dredging"， to develop the formula of Tongxinluo. Fundamental and clinical researches have demonstrated it can effectively protect the structure and function of myocardial microvascular endothelial cells， improve no reflow and reperfusion injury， and inhibit myocardial fibrosis after AMI， which further supports scientific value of the collaterals doctrine.

Analysis of Pathogenesis and Treatment of Chronic Coronary Syndrome Based on Vessel-collateral Theory / 中国实验方剂学杂志

Based on the syndrome and treatment system of collateral disease， and inheriting the development of the bloodline theory of traditional Chinese medicine （TCM）， academician WU Yi-ling systematically constructed the vessel-collateral theory of TCM and proposed that its core theory was the theory of Yingwei， that is， "Ying in the vein， and Wei outside the vein" （Huangdi Neijing·Lingshu·Yingwei Shenghui）， "obstructing of Yingwei， congelation of blood" （Treatise on Febrile Diseases· Pulse Differentiation Method）， "pathogen transferring through blood vessels， obstructed by blocking" （Jinkui Yaolue·Zangfu Jingluo Xianhou Bingmaizheng First）， and "damage of the heart， adjust its Yingwei". Based on the consistency of vessel-collateral as the channel of blood circulation in TCM with the blood vessels in western medicine， and guided by the Yingwei theory of vessel-collateral theory， the diagnostic criteria of syndrome differentiation of disease of vessel-collateral and vascular system represented by coronary heart disease， arrhythmia， heart failure and others was established to guide the prevention and treatment of vascular diseases. Based on the above analysis， guided by the Yingwei theory of vessel-collateral theory， and on the basis of related researches of vessel-collateral and vascular system， this paper discussed the etiology and pathogenesis of chronic coronary syndrome （CCS） in TCM. Taking useful collateral with unblocking as the treatment principle， the representative Tongluo prescription （Tongxinluo） was constructed， the research progress of Tongxinluo from various aspects such as animal experiment research， pharmacological research and clinical evidence-based research was summarized， a comprehensive system from etiology， pathogenesis， syndrome differentiation to treatment was formed， in order to provide new ideas for the clinical treatment of CCS.

Protective Effect of Tongxinluo Capsule on Cerebral Ischemia-reperfusion Injury and Its Mechanism of Action / 中国实验方剂学杂志

Objective:To study the protective effect of Tongxinluo capsule on cerebral ischemia-reperfusion injury, and explore the mechanism of Tongxinluo capsule in treating cerebral ischemia through network pharmacology. Method:The C57BL/6 mouse middle cerebral artery occlusion(MCAO) model was established by improved suture method and divided into sham operation group, model group, low, medium and high-dose Tongxinluo groups (crude drug 1,2,4 g·kg-1, intragastric administration), Aspirin group (2.055 g·L-1, intraperitoneal injection). Then, neurological function score and 2,3,5-triphenyltetrazole chloride(TTC) staining method were used to determine the infarct size of mice at 24, 48, 72 h by cerebral ischemia-reperfusion. First, chemical constituents of Tongxinluo capsule were screened from the BATMAN-TCM database, and the targets were analyzed. Then, gene ontology (GO) enrichment and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis were performed, and traditional Chinese medicine(TCM)-active ingredient-target network was constructed. Finally, the multi-dimensional pharmacological mechanism of Tongxinluo capsule in the treatment of cerebral ischemia was predicted. Result:Longa score, HE staining and TTC staining all suggested that Tongxinluo capsule could alleviate brain injury in mice after cerebral ischemia and reperfusion, and the improvement degree of Tongxinluo capsule on brain injury was gradually enhanced with the increase of Tongxinluo capsule dose. A total of 132 active components and 240 intersection targets, including cyclic adenosine monophosphate(cAMP)-dependent protein kinase catalytic subunit alpha (PRKACA), adenylate cyclase 1(ADCY1), serine/threonine kinase 1 (Akt1), dopamine receptor D2 (DRD2) and discs large homolog 4 (DLG4) were screened from 12 TCM in Tongxinluo capsule. GO was enriched in cationic channel activity, ion gated channel activity, gate channel activity, neurotransmitter receptor activity, ion channel activity, etc. KEGG was enriched in cAMP signaling pathway, calcium signaling pathway, neuroactive ligand-receptor interaction, cyclic guanosine monophosphate(cGMP)/protein kinase G(PKG) signaling pathway and dopaminergic synaptic signaling pathway. Conclusion:Tongxinluo capsule can alleviate brain damage in mice with cerebral ischemia-reperfusion, and achieve brain protection through multiple targets and multiple links. Network pharmacology reveals effective components，targets and pathway of Tongxinluo capsule in the treatment of cerebral ischemia, which provides theoretical support for the mechanism of Tongxinluo capsule in the treatment of cerebral ischemia.

Early Intervention of Tongxinluo () on Right Ventricular Function Assessed by Echocardiography in Rats with Pulmonary Arterial Hypertension Induced by Monocrotaline / 中国结合医学杂志

OBJECTIVE@#To investigate the effect of early intervention of Tongxinluo (, TXL) on right ventricular function (RVF) of rats with pulmonary arterial hypertension (PAH) induced by monocrotaline (MCT).@*METHODS@#A total of 30 adult male Sprague-Dawley rats were assigned to 5 groups with complete random experiment design: Sham group (Sham), MCT group, TXL group, sildenafil (SIL) group and combination group (TXL+SIL), 6 rats in each group. Rats were injected with 50 mg/kg MCT solution for inducing PAH model except for those in the sham group. From the day of modeling, rats of TXL, SIL and TXL+SIL groups were given TXL (1.2 g/kg), SIL (10 mg/kg) and combination solution (TXL:1.2 g/kg, SIL: 10 mg/kg) respectively, and rats in Sham and MCT groups were given normal saline (5 mL/kg). The samples were collected and tested after 21 consecutive days of intragastric administration. Echocardiography was used to measure the related indices of RVF, including pulmonary arterial flow spectrum, pulmonary artery diameter (PAD), right ventricular wall thickness (RVWT), right ventricular diameter (RVD), tricuspidannular plane systolic excursion (TAPSE), right atrium transverse diameter (RAT), and inferior vena cava diameter (IVCD). Elastic Verhoeff-Van Gieson staining was adopted to measure the percentage of wall thickness (WT%) of pulmonary arteriols. Hematoxylin-eosin staining was used to measure the cross-sectional area (CSA) of right ventricular cardiomyocytes.@*RESULTS@#MCT-induced PAH rat model was successfully established. In MCT group the wall of pulmonary arterioles exhibited a prominent-increase thickness, PAD, RVWT, RVD, RAT, IVCD, WT%, right ventricular hypertrophy index (RVHI) as well as CSA of RV cardiomyocyte significantly increased (all P<0.01), and TAPSE markedly decreased (P<0.01). At the same time, TXL prominently improved all of the above indices (all P<0.01). In comparison with SIL, TXL significantly reduced RVD (P<0.05) and decreased CAS of RV cardiomyocytes (P<0.01), but TAPSE in SIL group was much larger than in TXL group (P<0.01). Moreover, TAPSE in TXL+SIL group was larger than that in TXL group (P<0.01), while the two groups performed equally well in terms of the other indices.@*CONCLUSION@#Early intervention of TXL could inhibit pulmonary arterioles remodeling, and improve RVF by attenuating right ventricular hypertrophy, and TXL has a stronger effect on inhibiting right ventricular remodeling than SIL.

Clinical Effect of Jinlida and Tongxinluo on Type 2 Diabetic Kidney Disease Under Vessel Collateral Theory / 中国实验方剂学杂志

Objective: To observe the clinical efficacy of Jinlida (JLD) granules and Tongxinluo (TXL) capsules on type 2 diabetic kidney disease (DKD) under the guidance of vessel collateral theory. Method: A total of 120 patients with type 2 DKD, were randomly divided into 2 groups:the normal control group (60 cases) and the treatment group (60 cases). The patients in normal control group were treated with dietary control and hyperglycemia control. Based on treatment in control group, patients in treatment group were additionally treated with JLD granules (1 bag, tid), and TXL capsules (4 capsules, tid). The treatment was lasted for 12 weeks. The clinical efficacy, traditional Chinese medicine(TCM) syndrome scores were observed and compared before and after treatment. At the same time, the levels of glucose metabolism indexes including fasting blood glucose (FBG),postprandial 2 h plasma glucose (2 hPG), glycosylated hemoglobin (HbA1c) and the insulin resistance (IR); the levels of lipid metabolism indexes including total cholesterol(TC),triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and the high-density lipoprotein cholesterol (HDL-C); the levels of renal function indexes including urinary albumin excretion rate (UAER) and serum creatinine (SCr); as well as nailfold microcirculation were detected and compared. Result: ①The total effective rate was 80.0% in treatment group, significantly higher than 61.67% in the normal control group (PPPPPβ2-MG in treatment group was significantly obvious than that in the control group (PPConclusion: Tongxinluo combined with Jinlida can improve the clinical symptoms of patients with type 2 diabetic nephropathy and reduce urinary trace albumin, and its mechanism may be related to lowering glucose, regulating lipid metabolism and improving microcirculation.

Effects of Tongxinluo Capsules combined with routine treatment on Fib and MPV levels in appropriate patients for CABG surgery / 中成药

AIM To investigate the effects of Tongxinluo Capsules (Ginseng Radix et Rhizoma,Hirudo,Scorpio,etc.) combined with routine treatment on fibrinogen (Fib) and mean platelet volume (MPV) levels in appropriate patients for coronary artery bypass graft (CABG) surgery.METHODS One hundred and six patients were randomly assigned into control group (n =50) for routine treatment and observation group (n =56) for combination therapy of Tongxinluo Capsules and routine treatment.Both groups had their Fib and MPV levels evaluated,and safety compared.RESULTS Thirty,ninety days after the treatment,the two groups reported less incidence of composite cardiovascular events (refractory angina pectoris,relapsing myocardial infarction or death) (P ＜ 0.01),and the observation group had an even more obviously reduced plasma Fib level (P ＜0.01).The significantly decreased after-treatment MPV levels in the two groups were observed (P ＜ 0.05),and a most distinct decrease extent was found in the observation group after 90 d (P ＜ 0.05).For the bleeding events,the incidence rates of the observation group and the control group were 5.4％ and 4.0％,respectively.CONCLUSION For appropriate candidates of CABG surgery,Tongxinluo Capsules shows its efficacy in dissolving thrombus and improving clinical symptoms without serious bleeding risk.

Effects of Tongxinluo on High Glucose-induced Proliferation and Apoptosis of Cardiac Fibroblasts / 中国医科大学学报

Objective This study investigated the effect of tongxinluo (TXL) on high glucose-induced proliferation and apoptosis of cardiac fibroblasts (CFs),to explore the possible mechanism by which TXL inhibits myocardial fibrosis. Methods Primary culture and subculture of neonatal SD rat CFs was carried out as follows. Immunofluorescence staining was performed to identify CFs. The CFs were divided into control group (cultured with low-glucose DMEM),model group (cultured with high-glucose DMEM),and TXL treatment groups (cultured with high-glucose DMEM+TXL at 20,80,and 320 μg/mL). The proliferation of CFs in each group was detected by MTT assay. The expression of collagen typesⅠand Ⅲ in each group was detected by ELISA. Western blotting was used to detect the expression of bax and bcl-2 in each group. Results CFs Proliferation and collagen typesⅠandⅢsecretion were higher in the model group than in the control group. The CFs proliferation and collagen content in the TXL treatment groups were significantly lower than those in the model group. bcl-2 expression was significantly increased and bax expression was decreased in the model group,compared with the corresponding values in the control group. In comparison with the model group,bcl-2 expression was downregulated and bax expression was upregulated in the TXL treatment groups. Conclusion TXL can reduce the CFs proliferation and inhibit their collagen secretion under high glucose conditions. TXL also induces the CFs apoptosis by reducing bcl-2 expression and increasing bax expression. Thus,TXL can play a role in the treatment of myocardial fibrosis.

Effect of Tongxinluo Treated Conditioned Medium of Cardiac Microvascular Endothelial Cells on Rats' Embryo Cardiomyocyte Apoptosis / 中国循环杂志

Objective: To explore the effect of impaired cardiac microvascular endothelial cells on rat's embryo cardiomyocyte apoptosis and the impact of Tongxinluo in such process. Methods: 3 kinds conditioned medium of cardiac microvascular endothelial cells were prepared. ① normal rat's cardiac microvascular endothelial cell (RCMECs) conditioned medium, ②homocysteine induced impaired RCMECs conditioned medium and ③ Tongxinluo treated RCMECs conditioned medium. Rat's embryo H9c2 cardiomyocytes were divided into 4 groups:① Control group, cells were cultured in DMEM without serum, ② N-CM group, cells were cultured in RCMECs conditioned medium, ③ H-CM group, cells were cultured in homocysteine induced impaired RCMECs conditioned medium and ④ T-CM group, cells were cultured in Tongxinluo treated RCMECs conditioned medium. Cell mitochondrial membrane potential (MMP) was detected by JC-1 agent, ROS level was examined by flow cytometry, cardiomyocytes apoptosis was measured by live cell imaging system, expression levels of cytochrome C (Cyt-C), cysteinyl aspartate specific proteinase-3 (Caspase-3), Bcl-2 associated X protein (Bax) and B-cell leukemia/lymphoma 2 protein (Bcl-2) were detected by Western blot analysis. Results: MMP, expression levels of ROS, Cyt-C and cardiomyocyte apoptosis were similar between Control group and N-CM group, P>0.05. Compared with N-CM group, H-CM group had decreased MMP, increased ROS and cardiomyocyte apoptosis, up-regulated expressions of Cyt-C, Caspase-3 and Bax, all P<0.01. Compared with H-CM group, T-CM group had increased MMP, decreased ROS and cardiomyocyte apoptosis, down regulated expressions of Cyt-C, Caspase-3 and Bax, all P<0.05; while up-regulated expression of Bcl-2, P<0.01. Conclusion: Conditioned medium of impaired cardiac microvascular endothelial cells may induce cardiomyocyte apoptosis and such process could be inhibited by Tongxinluo.

Tongxinluo Capsule () for Cardiac Syndrome X: A Systematic Review and Meta-Analysis / 中国结合医学杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of Tongxinluo Capsule (, TXL) for patients with cardiac syndrome X (CSX).</p><p><b>METHODS</b>Randomized controlled trials (RCTs) regarding TXL in the treatment of CSX were searched in Chinese Biomedicine Literature Database, China National Knowledge Infrastructure, Chinese Scientific Journal Database, Wanfang Database, PubMed, EMBASE, Cochrane Central Register of Controlled Trial, websites of the Chinese and International Clinical Trial Registry platform up to June 30, 2015. The intervention was either TXL alone or TXL combined with conventional treatment, while the control intervention was conventional treatment with or without placebo. Data extraction, methodological quality assessment and data analyses were performed according to the Cochrane criteria. The primary outcome was a composite event of death, acute myocardial infarction (AMI), angina requiring hospitalization, revascularization, and heart failure. The secondary outcome measures were angina symptom improvement, electrocardiograph (ECG) improvement, and serum endothelin-1 (ET-1) level. The adverse events were also recorded. RevMan 5.3 software was applied for data analyses.</p><p><b>RESULTS</b>Twelve RCTs (696 patients) were included. Compared with conventional treatment, the addition of TXL to conventional treatment showed some benefits on relieving angina symptoms [risk ratio (RR): 1.46, 95% confidence interval (CI) (1.25, 1.71), P<0.01], and improving ECG [RR: 1.45, 95% CI (1.21, 1.74), P<0.01]. The pooled result did not support a benefit of TXL on reducing the incidence of primary outcome [RR: 0.20, 95% CI (0.02, 1.61), P=0.13]. In addition, TXL decreased serum ET-1 concentration of CSX patients [standardized mean number:-1.63, 95% CI (-2.29,-0.96), P<0.01]. No serious adverse events were reported.</p><p><b>CONCLUSIONS</b>TXL documents potential benefits on attenuating angina symptoms, improving ECG and decreasing serum ET-1 level for CSX patients. However, more rigorous RCTs with high quality are needed to confirm its efficacy and safety.</p>

Tongxinluo Improves Apolipoprotein E-Deficient Mouse Heart Function / 中华医学杂志(英文版)

<p><b>Background</b>Our previous studies have shown that Tongxinluo (TXL), a compound Chinese medicine, can decrease myocardial ischemia-reperfusion injury, protect capillary endothelium function, and lessen cardiac ventricle reconstitution in animal models. The aim of this study was to illuminate whether TXL can improve hypercholesterolemia-impaired heart function by protecting artery endothelial function and increasing microvascular density (MVD) in heart. Furthermore, we will explore the underlying molecular mechanism of TXL cardiovascular protection.</p><p><b>Methods</b>After intragastric administration of TXL (0.1 ml/10 g body weight) to C57BL/6J wild-type mice (n = 8) and ApoE-/- mice (n = 8), total cholesterol, high-density lipoprotein-cholesterol, very-low-density lipoprotein (VLDL)-cholesterol, triglyceride, and blood glucose levels in serum were measured. The parameters of heart rate (HR), left ventricular diastolic end diameter, and left ventricular systolic end diameter were harvested by ultrasonic cardiogram. The left ventricular ejection fraction, stroke volume, cardiac output, and left ventricular fractional shortening were calculated. Meanwhile, aorta peak systolic flow velocity (PSV), end diastolic flow velocity, and mean flow velocity (MFV) were measured. The pulsatility index (PI) and resistant index were calculated in order to evaluate the vascular elasticity and resistance. The endothelium-dependent vasodilatation was evaluated by relaxation of aortic rings in response to acetylcholine. Western blotting and real-time quantitative reverse transcription polymerase chain reaction were performed for protein and gene analyses of vascular endothelial growth factor (VEGF). Immunohistochemical detection was performed for myocardial CD34 expression. Data in this study were compared by one-way analysis of variance between groups. A value of P < 0.05 was considered statistically significant.</p><p><b>Results</b>Although there was no significant decrease of cholesterol level (F = 2.300, P = 0.240), TXL inhibited the level of triglyceride and VLDL (F = 9.209, P = 0.024 and F = 9.786, P = 0.020, respectively) in ApoE-/- mice. TXL improved heart function of ApoE-/- mice owing to the elevations of LVEF, SV, CO, and LVFS (all P < 0.05). TXL enhanced aortic PSV and MFV (F = 10.774, P = 0.024 and F = 11.354, P = 0.020, respectively) and reduced PI of ApoE-/- mice (1.41 ± 0.17 vs. 1.60 ± 0.17; P = 0.037). After incubation with 10 μmol/L acetylcholine, the ApoE-/- mice treated with TXL aortic segment relaxed by 44% ± 3%, significantly higher than control group mice (F = 9.280, P = 0.040). TXL also restrain the angiogenesis of ApoE-/- mice aorta (F = 21.223, P = 0.010). Compared with C57BL/6J mice, the MVD was decreased in heart tissue of untreated ApoE-/- mice (54.0 ± 3.0/mmvs. 75.0 ± 2.0/mm; F = 16.054, P = 0.010). However, TXL could significantly enhance MVD (65.0 ± 5.0/mmvs. 54.0 ± 3.0/mm; F = 11.929, P = 0.020) in treated ApoE-/- mice. In addition, TXL obviously increased the expression of VEGF protein determined by Western blot (F = 20.247, P = 0.004).</p><p><b>Conclusions</b>TXL obviously improves the ApoE-/- mouse heart function from different pathways, including reduces blood fat to lessen atherosclerosis; enhances aortic impulsivity, blood supply capacity, and vessel elasticity; improves endothelium-dependent vasodilatation; restraines angiogenesis of aorta-contained plaque; and enhances MVD of heart. The molecular mechanism of MVD enhancement maybe relate with increased VEGF expression.</p>

Clinical effect of Tongxinluo capsule in the treatment of women with microvascular angina / 中国基层医药

Objective To analyze the clinical effect of Tongxinluo capsule in the treatment of female patients with microvascular angina .Methods 122 female patients with microvascular angina pectoris were selected ,and they were randomly divided into conventional group and observation group ,61 cases in each group .On the basis of the two groups in the same treatment ,including antiplatelet ,lipid,the observation group was given Tongxinluo capsule orally , treatment for 3 months.The therapeutic effect was compared between the two groups .Results The total effective rate of the observation group was 93.44％,which of the conventional group was 80.33％,the difference between the two groups was statistically significant (χ2 =4.603,P=4.603).The total effective rate of exercise electrocardiogram ( ECG ) improvement in the observation group was 91.80％, which of the conventional group was 75.41％, the difference between the two groups was statistically significant (χ2 =4.552,P=0.048).Conclusion Tongxinluo capsule in the treatment of female patients with microvascular angina pectoris has good clinical curative effect ,it can obviously improve the clinical symptoms ,promote disease recover ,which is worthy of popularizing .

Effect of Tongxinluo capsule combined with metoprolol on elderly patients with coronary heart disease and angina pectoris and its influence on hemorheology and inflammatory factors / 中国基层医药

Objective To investigate the effect of Tongxinluo capsule combined with metoprolol on elderly patients with coronary heart disease and angina pectoris and its influence on hemorheology and inflammatory factors.Methods 135 elderly patients with angina pectoris of coronary heart disease were selected,and they were randomly divided into treatment group (68 cases) and control group (67 cases).The treatment group was treated with Tongxinluo capsule combined with metoprolol,while the control group was treated with metoprolol.The two groups were treated for 8 weeks.The curative effect of the two groups was compared,the number and duration of angina pectoris,the changes of hemorheology and inflammatory factors before and after treatment were compared.Results The total effective rate of the treatment group (94.12％) was higher than 76.12％ of the control group (P ＜ 0.05).After treatment,the frequency and duration of angina pectoris in the treatment group were (6.03 ± 1.21) times/week and (3.02 ± 0.76) min/time,respectively,which were significantly lower than those in the control group [(9.87 ± 1.46) times/week and (4.86 ± 0.98) min/time] (t =16.649,12.201,all P ＜ 0.05).After treatment,the whole blood viscosity at high shear rate [(3.76 ± 0.41) mPa/s],whole blood viscosity in low shear [(8.13 ± 0.76) mPa/s],plasma viscosity [(1.23 ± 0.08) mPa/s],erythrocyte aggregation index [(2.06 ± 0.27)],fibrinogen [(2.46 ± 0.41) g/L] in the treatment group were lower than those in the control group[(4.53 ± 0.52) mPa/s,(9.61 ± 0.89) mPa/s,(2.09 ± 0.27) mPa/s,(2.63 ± 0.35),(3.53 ± 0.62) g/L] (t =9.562,10.396,25.170,10.604,11.844,all P ＜ 0.05).After treatment,the interleukin-6 (IL-6) [(8.49 ± 1.76) pg/mL],intercellular adhesion molecule-1 (ICAM-1)[(85.25 ± 8.92) pg/mL],C reactive protein (CRP) [(8.74 ± 1.76) mg/L] in the treatment group were lower than those in the control group[IL-6 (11.32 ± 2.10) pg/mL,ICAM-1 (103.42 ± 10.72) pg/mL,CRP (14.98 ± 2.24)mg/L] (t =8.491,10.712,18.012,all P＜0.05).Conclusion Tongxinluo capsule combined with metoprolol in the treatment of elderly patients with coronary heart disease angina pectoris has obvious curative effect,and can improve the patients'blood rheology and inflammatory reaction.

Effects of Tongxinluo Capsules on Serum CyPA and MMP-9 Levels in Patients with Coronary Heart Disease after PCI / 中国药房

OBJECTIVE:To investigate the effects of Tongxinluo capsules on the levels of serum cyclophilin A (CyPA) and matrix metalloproteinase-9 (MMP-9) in patients with coronary heart disease (CHD) after percutaneous coronary intervention (PCI).METHODS:A total of 115 CHD patients undergoing PCI were randomly divided into control group (59 cases) and observation group (56 cases).Control group was given conventional treatment.Observation group was additionally given Tongxinluo capsules 0.78 g,3 times a day,for consecutive 6 months,on the basis of control group.The levels of CyPA and MMP-9 as well as the occurrence of ADR were observed in 2 groups before and after treatment.RESULTS:Before treatment,there was no statistical significance in serum level of CyPA and MMP-9 between 2 groups (P＞0.05).The levels of CyPA in 2 groups 1 d and 1 month after surgery as well as the level of CyPA in control group 6 months after surgery were all significantly higher than before surgery,but the observation group was significantly lower than the control group 1 and 6 months,this index was decreased gradually as time,with statistical significance (P＜0.05).There was no statistical significance in the levels of CyPA between 2 groups 1 d after surgery or in observation group between 6 months after surgery and before surgery (P＞0.05).The levels of MMP-9 in 2 groups 1 d and 1 month after surgery were significantly higher than before surgery,and the observation group was significantly lower than the control group,this index was decreased gradually as time,with statistical significance (P＜0.05).There was no statistical significance in the levels of MMP-9 of 2 groups between 6 months after surgery and before surgery(P＞0.05).There was no statistical significance in the incidence of ADR between 2 groups (P＞0.05).CONCLUSIONS:Based on routine treatment,Tongxinluo capsules can significantly reduce the levels of CyPA and MMP-9 in CHD patients after PCI.

Effects of Tongxinluo capsule and Shen Mai injection in treatment of patients with acute decompensated heart failure and its effect on level of left ventricular ejection fraction, hs-CRP, BNP and QTcd / 中国生化药物杂志

Objective To study the effects of Tongxinluo capsule and Shen Mai injection in treatment of patients with acute myocardial infarction and its effects on level of left ventricular ejection fraction (LVEF),high sensitive C-reactive protein (hs-CRP),natriuretic peptide (BNP) and QT in acute decompensated heart failure ( QTcd) .Methods 82 patients with acute decompensated heart failure were selected in our hospital from May 2014 to April 2015, those patiens were divided into observation group and control group according to the method of lottery, 41 cases each group.The control group was treated with basic treatment and Huangxin injection, and the obsevation group was treated with Tongxinluo capsule on the basis of the control group.The changes of blood pressure, heart rate, LVEF, hs-CRP, BNP and QTcd were compared between the two groups before and after treatment. Results After treatment, the total effective rate of the observation group was significantly higher than the control group [92.68% (38/41) vs 60.97%(25/41)](P<0.05).The heart rate of the observation group was significantly lower than the control group (P<0.05), but the blood pressure level of the two groups had no significant difference.The levels of BNP, hs-CRP and QTcd in the observation group were significantly higher than the control group [(45.98 ±4.57)% vs(39.07 ±3.12)%](P<0.05) L, BNP, hs-CRP and QTcd were significantly lower than the control group [(2432.12 ± 114.32)ng/L,(17.32 ±1.87) mg/L, (34.76 ±3.02) ms vs (3565.87 ±174.76) ng/L, (14.08 ±1.23) mg/L,(38.45 ±3.86)].Adverse reactions were not observed in the observation group and the control group.Conclusion Tongxinluo capsule combined with Shen Mai injection can effectively increase the left ventricular ejection fraction and reduce hs-CRP, BNP and QTcd in patients with acute decompensated heart failure.The clinical curative effect is good and the safety is high.

Effect of Tongxinluo on carotid artery stenosisthe,hs-CRP and D-Dimer in patients with cerebral infarction / 国际检验医学杂志

Objective To investigate the effect of Tongxinluo on carotid artery stenosis,and the levels of high sensitive C reactive protein(hs-CRP) and D-Dimer in patients with cerebral infarction.Methods 168 patients with cerebral infarction treated in this hospital from June 2014 to June 2015 were randomly divided into experimental group and control group,with 84 cases in each group.The patients in both group received routine treatment.In addition to that,patients in the experimental group also used Tongxinluo capsule for 6 months as a course of treatment.After a course of treatment,Doppler ultrasound diagnosis instrument was used to detect carotid arterial intima-media thickness,plaque area and carotid artery stenosis rate.Hs-CRP and D-Dimer levels were also detected.Results After treatment,the carotid arterial intima-media thickness,plaque area and carotid vascular stenosis rate in two group were significantly decreased(P<0.05),but the three indicators in experimental group were decreased more significantly(P<0.05).After a course of treatment,the levels of D-Dimer and hs-CRP in peripheral blood of the two groups were significantly decreased(P<0.05),but the content of D-Dimer and hs-CRP was much lower in the experimental group(P<0.05).Conclusion Tongxinluo treatment could effectively reduce the level of hs-CRP and D-Dimer in patients with cerebral infarction,and alleviate the carotid artery stenosis,which might be worthy of clinical application.