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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.
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Objective To observe the effects of Shexiang Baoxin pill combined with intracoronary injection of nicorandil on myocardial perfusion and short-term prognosis after primary percutaneous coronary intervention in patients with ST-segment elevation myocardial infarction. Methods 151 patients with acute myocardial infarction after PPCI were enrolled in this study. Those patients were admitted to our hospital during January 2017 to January 2018. According to the numerical randomization method, 51 patients were selected as routine treatment group (group A), 50 patients with intracoronary injection of nicorandil (group B) and 50 patients received intracoronary injection of nicorandil plus oral Shexiang Baoxin pills (group C). Intra-operative corrected TIMI frame count (cTFC), postoperative TIMI grade 3 blood flow ratio, 2-hour ECG ST segment fallback >50% index, the incidence of major adverse cardiovascular events (MACE) during hospitalization and the incidence of angina and MACE within 3 months after surgery were evaluated. Results cTFC, 2 hours postoperative ECG ST segment fall >50% index in group B and C were better than group A (P<0.05). The results from group C were better than group B. Group C exhibited better results than group B and C in post-operative angina pectoris 3 months after surgery (P<0.05). Conclusion Shexiang Baoxin pills combined with intra-coronary injection of nicorandil can improve myocardial perfusion and short-term prognosis after primary percutaneous coronary intervention in patients with ST-segment elevation myocardial infarction
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OBJECTIVE@#To investigate the regulatory roles of Shexiang Baoxin Pill (SXBXW) in neointimal formation and vascular smooth muscle cells (VSMCs) invasion and apoptosis as well as the potential molecular mechanisms using cultured VSMCs model of vascular injury (platelet-derived growth factor (PDGF)-BB-stimulated) in vitro.@*METHODS@#VSMCs were randomly assigned to 5 groups: blank, PDGF-BB (20 ng/mL+ 0.1% DMSO), SXBXW-L (PDGF-BB 20 ng/mL + SXBXW low dose 0.625 g/L), SXBXW-M (PDGF-BB 20 ng/mL + SXBXW medium dose 1.25 g/L) and SXBXW-H (PDGF-BB 20 ng/mL+ SXBXW high dose 2.5 g/L) group. Cell proliferation was assessed using cell counting kit-8 (CCK-8) assay and bromodeoxyuridine (BrdU) incorporation assay, the migration effects were detected by Transwell assay, cell apoptosis rate was measured by the Annexin V/propidium iodide (PI) apoptosis kit. The markers of contractile phenotype of VSMCs were detected with immunofluorescent staining. To validate the effects of miR-451 in regulating proliferation, migration and apoptosis treated with SXBXW, miR-451 overexpression experiments were performed, the VSMCs were exposed to PDGF-BB 20 ng/mL + 0.1% DMSO and later divided into 4 groups: mimic-NC (multiplicity of infection, MOI=50), SXBXW (1.25 g/L) + mimic-NC, mimic-miR451 (MOI=50), and SXBXW (1.25 g/L) + mimic-miR451, and alterations of proteins related to the miR-451 pathway were analyzed using Western blot.@*RESULTS@#PDGF-BB induced VSMCs injury causes acceleration of proliferation and migration. SXBXW inhibited phenotypic switching, proliferation and migration and promoted cell apoptosis in PDGF-BB-induced VSMCs. In addition, miR-451 was shown to be down-regulated in the VSMCs following PDGF-BB stimulation. SXBXW treatment enhanced the expression of miR-451 in PDGF-BB-induced VSMCs (P<0.05). Compared with SXBXW + mimic-NC and mimic-miR451 groups, the expression of tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (Ywhaz) and p53 was further reduced in SXBXW + mimic-miR451 group, while activating transcription factor 2 (ATF2) was increased in VSMCs (P<0.05).@*CONCLUSION@#SXBXW regulated proliferation, migration and apoptosis via activation of miR-451 through ATF2, p53 and Ywhaz in PDGF-BB-stimulated VSMCs.
Subject(s)
Humans , Apoptosis , Becaplermin/pharmacology , Cell Movement , Cell Proliferation , Cells, Cultured , Dimethyl Sulfoxide/pharmacology , Drugs, Chinese Herbal , Hyperplasia/metabolism , MicroRNAs/metabolism , Muscle, Smooth, Vascular , Myocytes, Smooth Muscle , Tumor Suppressor Protein p53/metabolismABSTRACT
Shexiang Baoxin pills （SBP） are prescribed based on Suhexiang Pills derived from the Formulary of the Bureau of Taiping People's Welfare Pharmacy （《太平惠民和剂局方》） in the Song Dynasty. As the classic Chinese patent medicine in warming and dredging with aromatics， SBP have been widely used in clinical treatment for 30 years by virtue of their unique efficacy in coronary atherosclerotic heart disease （CHD）. Angiogenesis is a biological process in which the body activates angiogenesis-related factors in the body to act on endothelial cells under local vascular injury， tumor growth， local inflammation， and other stimuli to promote the proliferation， migration， and infiltration of endothelial cells， and form new sprouting or non-sprouting blood vessels. As a new strategy for ischemic diseases such as CHD， therapeutic angiogenesis is of great significance in the prevention and treatment of CHD in promoting angiogenesis of ischemic myocardium and establishing effective collateral circulation. However， for the atherosclerotic plaque and tumor， angiogenesis promotion is a risk factor for accelerating the disease progression. Therefore， safe and effective regulation of ischemic myocardial angiogenesis has become the focus of the current prevention and treatment of CHD. Studies in recent years have shown that SBP can intervene in angiogenesis with multiple pathways and targets， which can exert therapeutic angiogenesis effect on CHD and also inhibit atherosclerotic plaque and tumor angiogenesis to varying degrees. This study reviewed the experimental and clinical trials on the regulatory effect of SBPs on angiogenesis in CHD to provide references for the research on Chinese medicine intervention in angiogenesis of CHD.
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ObjectiveTo develop a quantitative analysis of multi-components by single marker （QAMS） for determination of bufalin， cinobufagin and resibufogenin in Shexiang Baoxin pills， and to provide a method for improving the national standard of the pills. MethodHigh performance liquid chromatography （HPLC） was developed for simultaneous determination of bufalin， cinobufagin and resibufogenin in Shexiang Baoxin pills and the methodology validation was carried out. The chromatographic separation was performed on a Nucleosil 100-5 C18 column （4.6 mm×250 mm， 5 μm） with the mobile phase of acetonitrile -0.1% potassium dihydrogen phosphate aqueous solution （pH adjusted to 3.2 with phosphoric acid） （48∶52）， and the flow rate was 0.6 mL·min-1， the detection wavelength was set at 296 nm and the column temperature was 35 ℃. Taking cinobufagin as the internal standard， the relative correction factors （RCFs） of bufalin and resibufogenin were calculated， and the key influencing factors of RCFs were investigated. Relative retention time was used for the chromatographic peak location of the analyte， combining with the on-line ultraviolet spectroscopy and accurate relative molecular weight obtained by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry （UPLC-QTOF/MS）. The external standard method was used to verify the contents of three components obtained by QAMS. ResultQAMS was established for the determination of bufalin， cinobufagin and resibufogenin in the samples， and RCFs of cinobufagin to bufalin and resibufogenin were 0.922 and 1.01， respectively. The total content of the three marker compounds in 11 batches of Shexiang Baoxin pills was 33.7-36.0 µg per pill. There was no significant difference between the quantitative results of QAMS and external standard method. ConclusionThe established method can be used for the quality control of bufalin， cinobufagin and resibufogenin in Shexiang Baoxin pills. It is suggested that bufalin should be considered as one of three marker compounds， and the sum of bufalin， cinobufagin and resibufogenin should be used for the content limit of this preparation.
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Objective: To develop a GC-MS method for the simultaneous determination of six active constituents ( borneol, isoborneol, cinnamaldehyde, cinnamic acid, muscone and benzyl benzoate) in Shexiang Baoxin pills. Methods: A gas chromatogra-phy-mass spectrography (GC-MS) method was adopted using a DB-5 capillary column (30 m × 0. 25 mm,0. 1 μm). The column tem-perature was raised as the following program:the initial temperature was 70℃, maintained for 2 min, raised the temperature (5℃· min-1) to 150℃, maintained for 4 min and then raised the temperature (20℃·min-1) to 260℃, and maintained for 3 min. The range of mass-to-electric charge ratio was 10 to 425. Results:The calibration curves of borneol, isoborneol, cinnamaldehyde, cinnam-ic acid, muscone and benzyl benzoate were linear within the range of 0.022-22.000 μg·ml-1(r=0.999 6),0.024-24.000 μg· ml-1(r=0.999 6),0.028-28.000μg·ml-1(r=0.999 8),0.034-34.000μg·ml-1(r=0.999 6),0.040-40.000μg·ml-1(r=0.999 7) and 0.050-50. 000 μg·ml-1 (r =0.999 9), respectively. The average recovery was 97.20%, 97.40%, 97.53%, 99. 60%, 98. 78% and 98. 27% and RSD was 0. 89%, 1. 18%, 1. 52%, 1. 49%, 0. 79% and 1. 74%(n=6), respectively. Con-clusion:The method is accurate, suitable, convenient and reproducible, which can be used for the quality control of multi components in Shexiang Baoxin pills.
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OBJECTIVE:To compare the clinical efficacy and safety of Shexiang baoxin pills and Shensong yangsin capsules in the treatment of coronary heart disease complicated with chronic heart failure and premature ventricular contractions. METHODS:129 patients with chronic heart failure and premature ventricular contractions were randomly divided into blank group(n=43),ob-servation group(n=43)and control group(n=43). All groups received routine treatment as oxygen inhalation,diuretics. Control group additionally received Shensong yangsin capsules 4 pills for 3 times per day. Observation group additionally received Shexiang baoxin pills 2 pills for 3 times per day. Treatment course of 2 groups lasted for 3 months. Clinical efficacies of 2 groups were ob-served,and heart function,cardiovascular autonomic nervous function and vascular endothelial function were observed before and after treatment. RESULTS:Total effective rate of observation group was significantly higher than that of control group(P0.05). LVEF, NO of observation group were significantly higher than that of control group(P<0.05),IVST,LVDd,LVPWT,ET of observation group were significantly lower than that of control group(P<0.05). But control group and observation group were better than the blank group,and no obvious adverse reaction. CONCLUSIONS:Shexiang baoxin pills is more effective than Shensong yangsin cap-sules in the treatment of coronary heart disease complicated with chronic heart failure and premature ventricular contractions.
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Objective: To investigate the inhibition of Shexiang Baoxin Pills (SBP) on myocardial remodeling due to the development of hepatic cirrhosis and its mechanism. Methods: To induce hepatic fibrosis, 70 rats were administered with CCl4, twice daily for eight weeks. At the end of the week 2, 10 rats were executed, the liver tissues were HE stained to confirm the formation of hepatic fibrosis, and the rest rats were randomly and equally divided into benazepril[positive control, 10 mg/(kg·d)], SBP[45 mg/(kg·d)], and model groups. The rats were ig administered for six weeks. Ten rats from the total of eighty rats were taken as the normal control group. At the end of the week 8, the blood pressure of all rats was measured, the alanine transarninase (ALT) and aspartate aminotransferase (AST) levels in serum were detected, and the collagen contents in liver and myocardial tissues were measured by Masson staining. The expression of matrix metalloproteinases (MMP-9) and tissue inhibitor of metalloproteinase (TIMP-1) were detected by Western blotting, the contents of hydroxyproline, type I and type III collagen in myocardial tissue were measured by ELISA. The liver function and hepatic fibrosis of rats in each group were observed, and the left ventricular hypertrophy index (LVHI) was analyzed. Results: There were different degrees of liver function damage, liver fibrosis, and myocardial injury in the rats in the model group. Compared with the model group, SBP could obviously reduce the contents of ALT and AST in serum and hepatic collagen (P < 0.01), the expression of myocardial MMP-9 and TIMP-1, the contents of hydroxyproline, type I and type III collagen, blue-stained collagen, and LVHI (P < 0.05). The ratio of MMP-9/TIMP-1 was obviously heightened (P < 0.05). The indexes of rats in the benazepril group were improved at different degrees. Conclusion: There is no difference in the effect of anti-hepatic fibrosis and ameliorating myocardium remodeling between SBP and benazepril. SBP has better effect on protecting liver function with damage but has no influence on blood pressure. SBP has better holistic affect on the treatment of cirrhotic cardiomyopathy than benazepril.
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Objective:The stimulate angiogenes effect and mechanism of Shexiangbaoxin Pills on coronary collateral development in the hearts of experimental myocardial infarction rats were studied. Methods:24 myocardial infarction rats were randomly divided into 3 groups, 8 rats in group A were treated with Shexiangbaoxin Pills, 8 rats in group B were treated with Beifuji and heparin, and 8 rats in group C were treated with 0.9% normal saline as control. Infarct area, the contents of VEGF、bFGF and VⅢ factor, and vascular density in the edge of infarct section were measured after 6 weeks treating.Results: Infarct area in group A was obviously less than that in group C, the contents of VEGF、bFGF and VⅢ factor in the edge of infarct section and vascular density in group were significantly increased compared with those in group C. Conclusions: Shexiangbaoxin Pills could stimulate angiogenesis of the collateral branch of coronary artery in ischemic myocardium of rats and showed good protective on myocardial ischemia.
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AIM: To test and verify the effect of Shexiang Baoxin Pills(SXBXW) on treating acute vertigo. METHODS: Sixty patients with acute vertigo were randomly assigned to the treatment group(40 cases) and the control group(20 cases).The treatment group was given four pills of SXBXW by sublingually. The control group was drip-fed Betahistine Hydrochloride and Sodium Injection 250 mL. Both groups were drip-fed normal saline injection 250 mL plus Vitamine B_6 0.2g at the same time. RESULTS: After three hours of observation, both the drugs could significantly reduce the sympton of acute vertigo, and its therapeutic efficacies were similar. CONCLUSION: SXBXW has obvious therapeutic efficacy and less side effect.
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AIM: To establish the methods for determining borneol,isoborneol,muscone,benzyl benzoate in Shexiang Baoxin Pills. METHODS: Turbomass GC-MS instrument was used;the selective ion was applied for detecting borneol,isoborneol,muscone,benzyl benzoate.DB-5 capillary column(0.1 ?m?0.25 mm?30 m).The column temperature was rose by program from 80 ℃ to 260 ℃;the quantiative ion m/z 95 used for borneol and isoborneal,m/z 238 for musone,m/z 212 for benzyl benzoate;Shexiang Baoxin Pills were diluted with hexane. RESULTS: The linear ranges of borneol,isoborbeol,muscone,benzyl benzoate were within 0.020-20.0 ?g/mL(r=0.999 3),0.024-24.0 ?g/mL(r=0.999 0),0.029-28.8 ?g/mL(r=0.999 1),0.050-50.0 ?g/mL(r=(0.999 2)) respectively.The average recoveries of borneol,isoborbeol,muscone,benzyl benzoate were 97.00%,(96.30%,) 96.85%,98.20%,respectively. CONCLUSION: The method is simple accurate and highly sensitive and suitable for Shexiang Baoxin Pills.
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AIM:To observe the effect of Shexiang Baoxin Pills on pathologic changes and heart function of streptozotocin(STZ)-induced diabetic rats. METHODS:The rats were randomly divided into the control group,Shexiang Baoxin Pill group and STZ group.The rats in Shexiang Baoxin Pill group took Shexiang Baoxin Pill(50 mg/kg) to perfuse the stomach every day.The cardiac functions in 8 weeksafter treatment were determined.Meantime,the cardiac pathologic changes were observed through electron microscope and immunohistochemistry. RESULTS: Shexiang Baoxin Pills could reduce the interstitial fibrosis of myocardium in STZ rats.it could obviously improve the cardiac contraction and diastolic functions in STZ rats. CONCLUSION: Shexiang Baoxin Pills can(amendment) cardiac pathologic changes and improve cardiac function in STZ rats.