OBJECTIVE To identify the bioactive anti-angiogenic constitutes targeting tumor endothelial cells(TECs)in Shenmai Injection(SMI).METHEODS For pharmacokinetic(PK)studies,Balb/c mice harboring human colorectal cancer(Lo...OBJECTIVE To identify the bioactive anti-angiogenic constitutes targeting tumor endothelial cells(TECs)in Shenmai Injection(SMI).METHEODS For pharmacokinetic(PK)studies,Balb/c mice harboring human colorectal cancer(LoVo)xenografts were treated with SMI 10 mL·kg^-1 daily for 1 or 8 d.Multidimensional PK profiles of ginsenosides in plasma,subcutaneous tumors,and TECs were investigated.For PD studies,the tumor-bearing mice Intravital multi-photon imaging and CD31 immunofluorescence staining were used to evaluate the number of microves⁃sels and braches.Double staining of CD31 and α-SMA was performed to evaluate pericytes coverage ratios around vessels.ELISA was performed to determine the concentrations of VEGF and FGF in tumor tissues.For synergistic anti-tumor study,the tumor-bearing mice were treated with SMI 10 mL·kg^-1 daily,Rd 5 mg·kg^-1 daily with or without 5-FU 15 mg·kg^-1 every 3 d for 20 d.HPLC-MS/MS was used to determine the concentrations of 5-FU in plasma and tumor tissues.RESULTS SMI decreased the number of microvessels(P<0.05)and vessel branches(P<0.05)and improved vascular pericytes coverage(P<0.05).PK studies showed that the concentrations of protopanaxadiol-type(PPD)ginsenosides(Rb1,Rb2/Rb3,Rc,and Rd)in both,plasma and tumors,were higher than those of protopanaxatriol-type(Rg1 and Re)and oleanane-type(Ro)ginsenosides.Among PPD ginsenosides,Rd exhibited the greatest concentrations in tumors and TECs after repeated injection.In fact,the proportion of Rd in the detectable components of SMI gradually increased in the following order:SMI formula(2.8%),plasma(16.0%),tumor tissues(34.3%),and TECs(40.3%).In vivo bioactivity results showed that Rd 5 mg·kg^-1 daily significantly decreased the number of microvessels(P<0.05)and vessel branches(P<0.05)and increased pericytes coverage(P<0.05)while Rd 0.5 mg·kg^-1 daily,Rb1 and Rg1 had no significant effect on them.Rd 5 mg·kg^-1 suppressed the expression of VEGF and FGF simultaneously.Rd 5 mg·kg^-1 enhanced the antitumor effect of 5-FU via increasing the distribution of 5-FU in tumor tissues(P<0.05)in xenograft mice.CONCLUSION Ginsenoside Rd may be the major bioactive anti-angiogenic constituent targeting TECs after SMI treatment.展开更多
OBJECTIVE Shenmai Injection(SMI)is widely used in the treatment of cardiovascular diseases,such as heart failure and myocardial ischemia.In clinic,SMI showed protective effects on doxorubicin(Dox)-induced cardiac toxi...OBJECTIVE Shenmai Injection(SMI)is widely used in the treatment of cardiovascular diseases,such as heart failure and myocardial ischemia.In clinic,SMI showed protective effects on doxorubicin(Dox)-induced cardiac toxicity.In current study,we investigate the mitochondrial protective mechanisms of SMI on Dox-induced myocardial injury.METHODS C57BL/6 mice were divided into four groups:①control group;②Dox injury group;③SMI+Dox group and dexrazoxane(DRZ)+Dox group.Dex was a positive control.Myocardial injury was evaluated by echocardiography,HE and TUNEL staining,myocardial markers measurement.H9C2 cardiomyocytes pretreatment with SMI for 24 h were exposed to Dox.Cell viability and apoptosis were measured by CCK8,Hoechst33342 staining,and Annexin V/PI staining.MitoSOX,mitochondrial membrane potential,and mitochondrial respiratory function were measured to evaluate mito⁃chondrial function.RESULTS SMI decreased mortality rate of Dox-injected mice,serum CK and CK-MB levels in vivo.SMI significantly prevented Dox-induced cardiac dysfunction and apoptosis and increased expression level of PI3K,p-Akt,and p-GSK-3β.Moreover,SMI significantly inhibited Dox-induced apoptosis,mitochondrial ROS production,and reduction of mitochondrial membrane potential in H9C2 cells.Mechanismly,the cardio-protective effect of SMI was suppressed by PI3K inhibitor LY294002.CONCLUSION SMI prevents Dox-induced cardiotoxicity and mitochondrial damage through activation of PI3K/Akt signaling pathway.展开更多
<strong>Objective: </strong>This study is to observe the therapeutic effects of Shenmai injection on patients with hypertensive ICH and cerebrocardiac syndromes as well as its effects on prognosis. <str...<strong>Objective: </strong>This study is to observe the therapeutic effects of Shenmai injection on patients with hypertensive ICH and cerebrocardiac syndromes as well as its effects on prognosis. <strong>Methods:</strong> A total of 72 patients with severe hypertensive ICH and cerebrocardiac syndromes were selected and divided into the control group and the experimental group (Shenmai injection group) randomly, 36 patients in each group. The control group was treated by conventional therapy, while the experimental group was administrated by intravenous drip of the mixture of 50 ml Shenmai injection and 250 ml 5% glucose injection based on the treatment of the control group, once everyday, 2 weeks continuously. <strong>Results:</strong> Myocardial enzyme indexes of two groups at 3d, 7d and 14d were observed (Table 1). Myocardial enzyme index of the experimental group was improved quickly and significantly. Myocardial enzyme data of two groups at 3d, 7d and 14d were P < 0.05. According to the electrocardiographic examinations results, ECG anomalies of the experimental group at 7d and 14d were also improved quickly (P < 0.05). There are no evident anomalies in GCS scores of two groups at 7d, but GCS score of the experimental group at 14d of the medication was significantly higher than that of the control group (P < 0.05). <strong>Conclusions:</strong> Shenmai injection has some therapeutic effects on cerebral injuries and myocardial damages. It can treat brain and heart simultaneously, realize the goal of addressing both symptoms and root causes, and improve prognosis of patients with severe hypertensive ICH.展开更多
Objective: To investigate the effect of Shenmai injection combined with antiplatelet drugs on the plaque property and inflammatory response in patients with non-ST-segment elevation ACS. Methods: A total of 142 patien...Objective: To investigate the effect of Shenmai injection combined with antiplatelet drugs on the plaque property and inflammatory response in patients with non-ST-segment elevation ACS. Methods: A total of 142 patients with non-ST-segment elevation ACS who were treated in the hospital between June 2015 and September 2017 were divided into control group (n=71) and Shenmai injection group (n=71) by random number table method. Control group received antiplatelet drugs based on routine treatment, and Shenmai injection group received Shenmai injection combined with antiplatelet drugs on the basis of routine treatment. The differences in serum contents of plaque property-related indexes and inflammatory factors were compared between the two groups before and after treatment. Results: Before treatment, there was no significant difference in serum contents of metabolism indexes, lipid indexes, cell adhesion molecules and inflammatory factors between the two groups. After 1 week of treatment, serum metabolism indexes Hcy and UA contents of Shenmai injection group were lower than those of control group;serum lipid indexes ox-LDL and Lp-PLA2 contents were lower than those of control group;serum adhesion molecules sVCAM-1 and sICAM-1 contents were lower than those of control group;serum inflammatory factors IL-1β, IL-6, IL-17 and IL-23 contents were lower than those of control group. Conclusion: Adjuvant Shenmai injection therapy can further stabilize the plaques and inhibit the systemic inflammatory response in patients with non-ST-segment elevation ACS.展开更多
Objective: To explore the clinical value of sodium ferulate + Shenmai injection in the adjuvant treatment of acute myocardial infarction (AMI). Methods: A total of 119 patients with AMI who were treated in our hospita...Objective: To explore the clinical value of sodium ferulate + Shenmai injection in the adjuvant treatment of acute myocardial infarction (AMI). Methods: A total of 119 patients with AMI who were treated in our hospital between December 2014 and December 2017 were reviewed and divided into the control group (n=60) who received conventional western medicine +Shenmai injection therapy and the sodium ferulate group (n=59) who received conventional western medicine + sodium ferulate + Shenmai injection therapy. The differences in serum levels of myocardial injury markers, inflammatory mediators and ventricular remodeling-related indexes were compared between the two groups before treatment and after 2 weeks of treatment. Results: Before treatment, serum levels of myocardial injury markers, inflammatory mediators and ventricular remodeling-related indexes were not significantly different between the two groups. After 2 weeks of treatment, serum myocardial injury markers GMP-140, cTnT, MYO, NT-proBNP and H-FABP levels of sodium ferulate group were lower than those of control group;serum inflammatory mediators MCP-1, IL-18 and hs-CRP levels were lower than those of control group;serum ventricular remodeling-related indexes GDF-15, MMP-10 and CgA levels were lower than those of control group whereas IGF-1 level was higher than that of control group. Conclusion: Western medicine combined with sodium ferulate+ Shenmai injection therapy can effectively protect the myocardial function and inhibit the systemic inflammatory response and ventricular remodeling in patients with AMI.展开更多
Shenmai (BL 62) and Zhaohai (KI 6), first recorded in A Classic of Acupuncture and Moxibustion (针灸甲乙经), are respectively the starting point of the YangqiaoChannel and the Yinqiao Channel, and they are two of ... Shenmai (BL 62) and Zhaohai (KI 6), first recorded in A Classic of Acupuncture and Moxibustion (针灸甲乙经), are respectively the starting point of the YangqiaoChannel and the Yinqiao Channel, and they are two of the eight confluence points. Although records about the right-left compatible use of these two points can be found in documents, the same-side compatible use of them has never been heardabout. Inspired by the good therapeutic effects in the treatment of paralytic strabismus by means of the same-side compatible use of these two points1, the author has applied this compatible use of them in the treatment of craniofacial diseases and obtained obvious therapeutic effects. Some of the sample cases are reported in the following.
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<strong>Objective:</strong> To investigate the therapeutic effect of Shenmai Injection on postoperative cerebral vasospasm in patients with ruptured aneurysms. <strong>Methods:</strong> Seventy...<strong>Objective:</strong> To investigate the therapeutic effect of Shenmai Injection on postoperative cerebral vasospasm in patients with ruptured aneurysms. <strong>Methods:</strong> Seventy patients undergoing craniotomy for ruptured aneurysms in our hospital were selected as study subjects and randomly divided into control (n = 33) and research (n = 37) groups, they were treated with nimodipine and nimodipine combined with Shenmai injection after operation. The blood flow velocity in the middle cerebral artery (MCA) before and at 1, 3, 7, 11 and 14 days after surgery and the incidence of cerebral vasospasm during these days were compared, and the GCS scores at 14 days postoperatively and GOS scores at 6 months postoperatively were compared between the two groups.<strong> Results:</strong> There were no statistically significant differences in the occurrence of cerebral vasospasm, GCS or GOS scores between the two groups (<em>P</em> > 0.05), but the period of postoperative cerebral vasospasm in the study group was significantly shorter than that in the control group. <strong>Conclusion:</strong> Shenmai injection has the effect of shortening the cycle of occurrence of cerebral vasospasm after the operation of ruptured aneurysms, promoting patients to recover as early as possible and reducing their physical and mental burden.展开更多
Objective: To study the effect of Shenmai injection combined with irbesartan on the microinflammatory state and nutritional status of patients with peritoneal dialysis. Methods:A total of 108 patients with end-stage r...Objective: To study the effect of Shenmai injection combined with irbesartan on the microinflammatory state and nutritional status of patients with peritoneal dialysis. Methods:A total of 108 patients with end-stage renal disease who received peritoneal dialysis in Guangyuan First People's Hospital between May 2014 and November 2016 were selected and randomly divided into two groups, the combined group received Shenmai injection combined with irbesartan therapy, and the ARB group received irbesartan therapy. The renal function indicators, inflammatory response indicators and nutritional status indicators of the two groups were detected before treatment as well as 3 months and 6 months after treatment. Results: Scr, BUN and RRF of both groups 3 months and 6 months after treatment were not significantly different from those before treatment;serum SAA, CRP, PAPP-A, CHE, TNF-α, IL-6 and IL-8 contents of both groups 3 months and 6 months after treatment were significantly lower than those before treatment, and serum SAA, CRP, PAPP-A, CHE, TNF-α, IL-6 and IL-8 contents of combined group 3 months and 6 months after treatment were significantly lower than those of ARB group;serum Alb, PA and Tf contents as well as mid-arm muscle circumference and mid-arm circumference of combined group 3 months and 6 months after treatment were not significantly different from those before treatment while serum Alb, PA and Tf contents as well as mid-arm muscle circumference and mid-arm circumference of control group 3 months and 6 months after treatment were significantly lower than those before treatment. Conclusion: Shenmai injection combined with irbesartan for peritoneal dialysis can reduce the microinflammatory state and improve the nutritional status.展开更多
Background:To evaluate the efficacy and safety of the classic ancient prescription Shenmai injection(the classic ancient presciption)combined with Western medicine in the treatment of acute pancreatitis.Method:PubMed,...Background:To evaluate the efficacy and safety of the classic ancient prescription Shenmai injection(the classic ancient presciption)combined with Western medicine in the treatment of acute pancreatitis.Method:PubMed,the Cochrane Library,EMBASE,the Web of Science,China National Knowledge Infrastructure,Wanfang database,VIP Database and Chinese BioMedicine Literature Database were searched from database establishment to January 2021.After 2 researchers independently screened the literature,extracted data and evaluated the bias risk included in the study.A meta-analysis of randomized controlled trials of the classic ancient prescription Shenmai injection combined with Western medicine in the treatment of acute pancreatitis was conducted with the Revman 5.0 software.Result:A total of 19 randomized controlled trials were included,including 1,507 patients.The results of meta-analysis showed that the test group had advantage over the control group in total effective rate(RR=1.23,95%CI(1.17,1.34),P<0.00001),serum amylase level(stand mean difference=−2.92,95%CI(−3.75,−2.09),P<0.00001),C-reactive protein level and IL-6 level with statistically significant.Conclusion:The current evidence shows that the classic ancient prescription Shenmai injection combined with Western medicine can achieve better curative effect in the treatment of acute pancreatitis than using Western medicine alone.It has more advantages in terms of the total effective rate,reducing the level of serum amylase level and inflammatory cytokines.展开更多
Objective: To explore effects of Shenmai Injection(参麦注射液) combined with Meglumine Adenosine Cyclophosphate Injection on cardiac function and peripheral serum levels of tumor necrosis factor-α(TNF-α), transformi...Objective: To explore effects of Shenmai Injection(参麦注射液) combined with Meglumine Adenosine Cyclophosphate Injection on cardiac function and peripheral serum levels of tumor necrosis factor-α(TNF-α), transforming growth factor-β1(TGF-β1) and interferon-γ(IFN-γ) in patients with viral myocarditis.Methods: A total of 70 patients with viral myocarditis admitted in Cardiovascular Medicine Department of our hospital from June 2016 to June 2018 were selected and divided into a control group(treated with Meglumine Adenosine Cyclophosphate Injection) and an observation group(additionally treated with Shenmai Injection(参麦注射液) on the treatment basis of the control group) according to random number method, with 35 cases in each group.Before and after the treatment, cardiac functional indexes like cardiac index(CI), left ventricular ejection fraction(LVEF) and left ventricular shortening fraction(FS), serum levels of TNF-α, TGF-β1 and IFN-γ, clinical efficacy and adverse reactions occurred in the 2 groups were recorded and compared.Results: Therapeutic effective rate in the observation group was 88.57%, higher than 68.57% in the control group(P < 0.05).After the treatment, cardiac functional indexes like CI, LVEF and FS were higher than those in the control group(P < 0.05).After the treatment, the serum expression levels of TNF-α and TGF-β1 were lower than those in the control group(P < 0.05), while the serum expression level of IFN-γ was higher than that in the control group(P < 0.05).There was no statistically significant difference in the adverse reaction rates between the 2 groups(P > 0.05).Conclusion: The treatment of patients with viral myocarditis by Shenmai Injection(参麦注射液) combined with Meglumine Adenosine Cyclophosphate Injection is more effective, reducing inflammation and restoring cardiac function.展开更多
In this paper,the feasibility and advantages of employing high performance liquid chromatographic(HPLC) fingerprints combined with pattern recognition techniques for quality control of Shenmai injection were investiga...In this paper,the feasibility and advantages of employing high performance liquid chromatographic(HPLC) fingerprints combined with pattern recognition techniques for quality control of Shenmai injection were investigated and demonstrated.The Similarity Evaluation System was employed to evaluate the similarities of samples of Shenmai injection,and the HPLC generated chromatographic data were analyzed using hierarchical clustering analysis(HCA) and soft independent modeling of class analogy(SIMCA).Consistent results were obtained to show that the authentic samples and the blended samples were successfully classified by SIMCA,which could be applied to accurate discrimination and quality control of Shenmai injection.Furthermore,samples could also be grouped in accordance with manufacturers.Our results revealed that the developed method has potential perspective for the original discrimination and quality control of Shenmai injection.展开更多
Objective: To evaluate the dynamic change of Th1/Th2 cytokines in serum, peritoneal lavage fluid (PLF) and splenic macrophages (SM) in rats with severe peritonitis, and to observe the therapeutic effects of recombinan...Objective: To evaluate the dynamic change of Th1/Th2 cytokines in serum, peritoneal lavage fluid (PLF) and splenic macrophages (SM) in rats with severe peritonitis, and to observe the therapeutic effects of recombinant interleukin-12 (rIL-2) and Shenmai injection (SMI, 参麦注射液), a Chinese medicinal preparation.Methods: Severe peritonitis (SP) model was induced by intraperitoneal injection of E. coli and B. frag, and mild peritonitis (MP) model was induced by cecal ligation and punching. Then the following experiments were done: (1) Survival rates of animals after every 6 hrs in the 72 hrs after modeling were recorded, serum and PLF levels of cytokines, including tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), and interleukin-10 (IL-10), 6 hrs, 12 hrs, 24 hrs and 48 hrs after modeling were measured. (2) Model rats were treated with rIL-12 or SMI, the survival rate was recorded and serum levels of TNF-α, INF-γ, and IL-10 before and after treatment were measured, and (3) amount of these cytokines produced by SM were determined 6 hrs, 12 hrs and 24 hrs after treatment. The survival rates and levels of cytokines were then compared between the groups (model group treated with rIL-12 or SMI, untreated model group, and blank group).Results: Serum and PLF levels of IFN-γ, TNF-α at all the time points in SP rats were significantly lower than those in MP rats while those of IL-10 6 hrs and 12 hrs after modeling were significantly higher in the former than that in the latter (P<0.05). IFN-γ secretion of SM in SP rats was significantly higher than that in MP rats 6 hrs after modeling (P<0.05). Administration of rlL-12 or SMI given before modeling could improve the survival rate of the model rats (P<0.05) and cause significant increase of the serum level and SM secretion of IFN-γ. Conclusion: Imbalance in promoting/antagonizing inflammatory cytokines and Th2 response dominance appear in SP rats early at the initiating stage, and SM secretion of inflammation promoting factor also reduces. Administration in time of rIL-12 and SMI, may increase the survival rate, and its mechanism may be related with their immuno-stimulating action.展开更多
Objective: To study effects of Shenmai Injection on hypertensive heart failure and its mechanism for inhibiting myocardial fibrosis. Methods: Salt-sensitive(Dahl/SS) rats were fed with normal diet(0.3% Na Cl) and the ...Objective: To study effects of Shenmai Injection on hypertensive heart failure and its mechanism for inhibiting myocardial fibrosis. Methods: Salt-sensitive(Dahl/SS) rats were fed with normal diet(0.3% Na Cl) and the high-salt diet(8% Na Cl) to observe the changes in blood pressure and heart function, as the control group and the model group. Salt-insensitive rats(SS-13BN) were fed with the high-salt diet(8% Na Cl) as the negative control group. After modeling, the model rats were randomly divided into heart failure(HF) group, Shenmai Injection(SMI) group and pirfenidone(PFD) group by a random number table, with 6 rats in each group. They were given sterilized water, SMI and pirfenidone, respectively. Blood pressure, cardiac function, fibrosis and related molecular expression were detected by sphygmomanometer, echocardiogram, enzyme linked immunosorbent assay(ELISA),hematoxylin-eosin staining, Masson staining, immunofluorescence and qPCR analysis. Results: After high-salt feeding, compared with the control and negative control group, in the model group the blood pressure increased significantly, the left ventricular ejection fraction(LVEF) and left ventricular fraction shortening(LVFS) were significantly reduced, and the serum NT-pro BNP concentration increased significantly(all P<0.05);furthermore,the arrangement of myocardial cells was disordered, the edema was severe, and the degree of myocardial fibrosis was also significantly increased(P<0.05);the protein and m RNA expressions of collagen type Ⅰ(Col Ⅰ) were up-regulated(P<0.05), and the mRNA expressions of transforming growth factor β1(TGF-β1), Smad2 and Smad3 were significantly up-regulated(P<0.05). Compared with HF group, after intervention of Shenmai Injection, LVEF and LVFS increased, myocardial morphology was improved, collagen volume fraction decreased significantly(P<0.05), and the mRNA expressions of Col Ⅰ, TGF-β1, Smad2 and Smad3, as well as Col Ⅰprotein expression, were all significantly down-regulated(all P<0.05). Conclusion: Myocardial fibrosis is the main pathological manifestation of hypertensive heart failure, and Shenmai Injection could inhibit myocardial fibrosis and effectively improve heart failure by regulating TGF-β1/Smad signaling pathway.展开更多
目的对参麦注射液应用于慢性阻塞性肺疾病(COPD)伴呼吸衰竭的有效性及安全性进行Meta分析。方法检索中国知网、万方数据库、维普资讯、中国生物医学文献数据库、PubMed、Cochrane Library、Web of Science、Embase医学文献数据库,由2位...目的对参麦注射液应用于慢性阻塞性肺疾病(COPD)伴呼吸衰竭的有效性及安全性进行Meta分析。方法检索中国知网、万方数据库、维普资讯、中国生物医学文献数据库、PubMed、Cochrane Library、Web of Science、Embase医学文献数据库,由2位研究者根据纳入、排除标准独立筛选文献,提取相应研究信息并交叉核对,筛选出参麦注射液治疗COPD伴呼吸衰竭的随机对照试验,使用RevMan5.4软件对纳入研究进行Meta分析,并使用GRADE评价系统对结局指标质量进行分级。结果本研究纳入16项临床研究,共1313例患者,观察组667例,对照组646例;参麦注射液联合西医常规治疗COPD伴呼吸衰竭患者,在临床总有效率[OR=3.10,95%CI(2.05~4.70),P<0.00001]、氧分压[MD=7.98,95%CI(4.97~11.00),P<0.00001]、二氧化碳分压[MD=-8.31,95%CI(-11.11~-5.51),P<0.00001]、C反应蛋白(CRP)[SMD=-1.64,95%CI(-2.37~-0.91),P<0.00001]、第一秒用力呼气容积(FEV1)[MD=0.38,95%CI(0.33~0.42),P<0.00001]方面,相较对照组差异有统计学意义(P<0.01);用力肺活量(FVC)两组间差异无统计学意义(P>0.05)。GRADE证据分级结果提示,总有效率、动脉血气氧分压、动脉血气二氧化碳分压、CRP、FVC、FEV1为极低级质量证据。结论西医常规结合参麦注射液治疗COPD合并呼吸衰竭可以提高临床治疗总有效率,改善低氧血症和(或)二氧化碳潴留,减轻炎症,安全性较好。展开更多
Shenmai injection(SMI)is a well-defined herbal preparation that is widely and clinically used as an adjuvant therapy for cancer.Previously,we found that SMI synergistically enhanced the activity of chemotherapy on col...Shenmai injection(SMI)is a well-defined herbal preparation that is widely and clinically used as an adjuvant therapy for cancer.Previously,we found that SMI synergistically enhanced the activity of chemotherapy on colorectal cancer by promoting the distribution of drugs in xenograft tumors.However,the underlying mechanisms and bioactive constituents remained unknown.In the present work,the regulatory effects of SMI on tumor vasculature were determined,and the potential anti-angiogenic components targeting tumor endothelial cells(TECs)were identified.Multidimensional pharmacokinetic profiles of ginsenosides in plasma,subcutaneous tumors,and TECs were investigated.The results showed that the concentrations of protopanaxadiol-type(PPD)ginsenosides(Rb1,Rb2/Rb3,Rc,and Rd)in both plasma and tumors,were higher than those of protopanaxatriol-type(Rg1 and Re)and oleanane-type(Ro)ginsenosides.Among PPD-type ginsenosides,Rd exhibited the greatest concentrations in tumors and TECs after repeated injection.In vivo bioactivity results showed that Rd suppressed neovascularization in tumors,normalized the structure of tumor vessels,and improved the anti-tumor effect of 5-fluorouracil(5 FU)in xenograft mice.Furthermore,Rd inhibited the migration and tube formation capacity of endothelial cells in vitro.In conclusion,Rd may be an important active form to exert the anti-angiogenic effect on tumor after SMI treatment.展开更多
Objective:To examine the effect of Shenmai Injection(SMJ)on ferroptosis during myocardial ischemia reperfusion(I/R)injury in rats and the underlying mechanism.Methods:A total of 120SPF-grade adult male SD rats,weighin...Objective:To examine the effect of Shenmai Injection(SMJ)on ferroptosis during myocardial ischemia reperfusion(I/R)injury in rats and the underlying mechanism.Methods:A total of 120SPF-grade adult male SD rats,weighing 220–250 g were randomly divided into different groups according to a random number table.Myocardial I/R model was established by occluding the left anterior descending artery for 30 min followed by 120 min of reperfusion.SMJ was injected intraperitoneally at the onset of 120 min of reperfusion,and erastin(an agonist of ferroptosis),ferrostatin-1(Fer-1,an inhibitor of ferroptosis)and ML385(an inhibitor of nuclear factor erythroid-2 related factor 2(Nrf2))were administered intraperitoneally separately 30 min before myocardial ischemia as different pretreatments.Cardiac function before ischemia,after ischemia and after reperfusion was analysed.Pathological changes in the myocardium and the ultrastructure of cardiomyocytes were observed,and the myocardial infarction area was measured.Additionally,the concentration of Fein heart tissues and the levels of creatine kinase-MB(CK-MB),troponin I(cTnI),malondialdehyde(MDA)and superoxide dismutase(SOD)in serum were measured using assay kits,and the expressions of Nrf2,glutathione peroxidase 4(GPX4)and acyl-CoA synthetase long-chain family member 4(ACSL4)were examined by Western blot.Results:Compared with the sham group,I/R significantly injured heart tissues,as evidenced by the disordered,ruptured and oedematous myocardial fibres;the increases in infarct size,serum CK-MB,cTnI and MDA levels,and myocardial Feconcentrations;and the decreases in SOD activity(P<0.05).These results were accompanied by ultrastructural alterations to the mitochondria,increased expression of ACSL4 and inhibited the activation of Nrf2/GPX4 signalling(P<0.05).Compared with the I/R group,pretreatment with 9 mL/kg SMJ and 2 mg/kg Fer-1 significantly reduced myocardial I/R injury,Feconcentrations and ACSL4 expression and attenuated mitochondrial impairment,while 14 mg/kg erastin exacerbated myocardial I/R injury(P<0.05).In addition,cardioprotection provided by 9 mL/kg SMJ was completely reversed by ML385,as evidenced by the increased myocardial infarct size,CK-MB,cTnI,MDA and Feconcentrations,and the decreased SOD activity(P<0.05).Conclusions:Ferroptosis is involved in myocardial I/R injury.Pretreatment with SMJ alleviated myocardial I/R injury by activating Nrf2/GPX4 signalling-mediated ferroptosis,thereby providing a strategy for the prevention and treatment of ischemic heart diseases.展开更多
基金National Nature Science Foundation of China(81773989and 81530098)
文摘OBJECTIVE To identify the bioactive anti-angiogenic constitutes targeting tumor endothelial cells(TECs)in Shenmai Injection(SMI).METHEODS For pharmacokinetic(PK)studies,Balb/c mice harboring human colorectal cancer(LoVo)xenografts were treated with SMI 10 mL·kg^-1 daily for 1 or 8 d.Multidimensional PK profiles of ginsenosides in plasma,subcutaneous tumors,and TECs were investigated.For PD studies,the tumor-bearing mice Intravital multi-photon imaging and CD31 immunofluorescence staining were used to evaluate the number of microves⁃sels and braches.Double staining of CD31 and α-SMA was performed to evaluate pericytes coverage ratios around vessels.ELISA was performed to determine the concentrations of VEGF and FGF in tumor tissues.For synergistic anti-tumor study,the tumor-bearing mice were treated with SMI 10 mL·kg^-1 daily,Rd 5 mg·kg^-1 daily with or without 5-FU 15 mg·kg^-1 every 3 d for 20 d.HPLC-MS/MS was used to determine the concentrations of 5-FU in plasma and tumor tissues.RESULTS SMI decreased the number of microvessels(P<0.05)and vessel branches(P<0.05)and improved vascular pericytes coverage(P<0.05).PK studies showed that the concentrations of protopanaxadiol-type(PPD)ginsenosides(Rb1,Rb2/Rb3,Rc,and Rd)in both,plasma and tumors,were higher than those of protopanaxatriol-type(Rg1 and Re)and oleanane-type(Ro)ginsenosides.Among PPD ginsenosides,Rd exhibited the greatest concentrations in tumors and TECs after repeated injection.In fact,the proportion of Rd in the detectable components of SMI gradually increased in the following order:SMI formula(2.8%),plasma(16.0%),tumor tissues(34.3%),and TECs(40.3%).In vivo bioactivity results showed that Rd 5 mg·kg^-1 daily significantly decreased the number of microvessels(P<0.05)and vessel branches(P<0.05)and increased pericytes coverage(P<0.05)while Rd 0.5 mg·kg^-1 daily,Rb1 and Rg1 had no significant effect on them.Rd 5 mg·kg^-1 suppressed the expression of VEGF and FGF simultaneously.Rd 5 mg·kg^-1 enhanced the antitumor effect of 5-FU via increasing the distribution of 5-FU in tumor tissues(P<0.05)in xenograft mice.CONCLUSION Ginsenoside Rd may be the major bioactive anti-angiogenic constituent targeting TECs after SMI treatment.
基金National Natural Science Foundation of China(8177401781202779+2 种基金81973624)Natural Science Foundation of Tianjin City(19JCYBJC28200)the Scientific Research Project of Tianjin Education Commission(2017KJ140)
文摘OBJECTIVE Shenmai Injection(SMI)is widely used in the treatment of cardiovascular diseases,such as heart failure and myocardial ischemia.In clinic,SMI showed protective effects on doxorubicin(Dox)-induced cardiac toxicity.In current study,we investigate the mitochondrial protective mechanisms of SMI on Dox-induced myocardial injury.METHODS C57BL/6 mice were divided into four groups:①control group;②Dox injury group;③SMI+Dox group and dexrazoxane(DRZ)+Dox group.Dex was a positive control.Myocardial injury was evaluated by echocardiography,HE and TUNEL staining,myocardial markers measurement.H9C2 cardiomyocytes pretreatment with SMI for 24 h were exposed to Dox.Cell viability and apoptosis were measured by CCK8,Hoechst33342 staining,and Annexin V/PI staining.MitoSOX,mitochondrial membrane potential,and mitochondrial respiratory function were measured to evaluate mito⁃chondrial function.RESULTS SMI decreased mortality rate of Dox-injected mice,serum CK and CK-MB levels in vivo.SMI significantly prevented Dox-induced cardiac dysfunction and apoptosis and increased expression level of PI3K,p-Akt,and p-GSK-3β.Moreover,SMI significantly inhibited Dox-induced apoptosis,mitochondrial ROS production,and reduction of mitochondrial membrane potential in H9C2 cells.Mechanismly,the cardio-protective effect of SMI was suppressed by PI3K inhibitor LY294002.CONCLUSION SMI prevents Dox-induced cardiotoxicity and mitochondrial damage through activation of PI3K/Akt signaling pathway.
文摘<strong>Objective: </strong>This study is to observe the therapeutic effects of Shenmai injection on patients with hypertensive ICH and cerebrocardiac syndromes as well as its effects on prognosis. <strong>Methods:</strong> A total of 72 patients with severe hypertensive ICH and cerebrocardiac syndromes were selected and divided into the control group and the experimental group (Shenmai injection group) randomly, 36 patients in each group. The control group was treated by conventional therapy, while the experimental group was administrated by intravenous drip of the mixture of 50 ml Shenmai injection and 250 ml 5% glucose injection based on the treatment of the control group, once everyday, 2 weeks continuously. <strong>Results:</strong> Myocardial enzyme indexes of two groups at 3d, 7d and 14d were observed (Table 1). Myocardial enzyme index of the experimental group was improved quickly and significantly. Myocardial enzyme data of two groups at 3d, 7d and 14d were P < 0.05. According to the electrocardiographic examinations results, ECG anomalies of the experimental group at 7d and 14d were also improved quickly (P < 0.05). There are no evident anomalies in GCS scores of two groups at 7d, but GCS score of the experimental group at 14d of the medication was significantly higher than that of the control group (P < 0.05). <strong>Conclusions:</strong> Shenmai injection has some therapeutic effects on cerebral injuries and myocardial damages. It can treat brain and heart simultaneously, realize the goal of addressing both symptoms and root causes, and improve prognosis of patients with severe hypertensive ICH.
文摘Objective: To investigate the effect of Shenmai injection combined with antiplatelet drugs on the plaque property and inflammatory response in patients with non-ST-segment elevation ACS. Methods: A total of 142 patients with non-ST-segment elevation ACS who were treated in the hospital between June 2015 and September 2017 were divided into control group (n=71) and Shenmai injection group (n=71) by random number table method. Control group received antiplatelet drugs based on routine treatment, and Shenmai injection group received Shenmai injection combined with antiplatelet drugs on the basis of routine treatment. The differences in serum contents of plaque property-related indexes and inflammatory factors were compared between the two groups before and after treatment. Results: Before treatment, there was no significant difference in serum contents of metabolism indexes, lipid indexes, cell adhesion molecules and inflammatory factors between the two groups. After 1 week of treatment, serum metabolism indexes Hcy and UA contents of Shenmai injection group were lower than those of control group;serum lipid indexes ox-LDL and Lp-PLA2 contents were lower than those of control group;serum adhesion molecules sVCAM-1 and sICAM-1 contents were lower than those of control group;serum inflammatory factors IL-1β, IL-6, IL-17 and IL-23 contents were lower than those of control group. Conclusion: Adjuvant Shenmai injection therapy can further stabilize the plaques and inhibit the systemic inflammatory response in patients with non-ST-segment elevation ACS.
基金Youth Projects of Hubei Provincial Natural Science Foundation No:2016CFB344.
文摘Objective: To explore the clinical value of sodium ferulate + Shenmai injection in the adjuvant treatment of acute myocardial infarction (AMI). Methods: A total of 119 patients with AMI who were treated in our hospital between December 2014 and December 2017 were reviewed and divided into the control group (n=60) who received conventional western medicine +Shenmai injection therapy and the sodium ferulate group (n=59) who received conventional western medicine + sodium ferulate + Shenmai injection therapy. The differences in serum levels of myocardial injury markers, inflammatory mediators and ventricular remodeling-related indexes were compared between the two groups before treatment and after 2 weeks of treatment. Results: Before treatment, serum levels of myocardial injury markers, inflammatory mediators and ventricular remodeling-related indexes were not significantly different between the two groups. After 2 weeks of treatment, serum myocardial injury markers GMP-140, cTnT, MYO, NT-proBNP and H-FABP levels of sodium ferulate group were lower than those of control group;serum inflammatory mediators MCP-1, IL-18 and hs-CRP levels were lower than those of control group;serum ventricular remodeling-related indexes GDF-15, MMP-10 and CgA levels were lower than those of control group whereas IGF-1 level was higher than that of control group. Conclusion: Western medicine combined with sodium ferulate+ Shenmai injection therapy can effectively protect the myocardial function and inhibit the systemic inflammatory response and ventricular remodeling in patients with AMI.
文摘 Shenmai (BL 62) and Zhaohai (KI 6), first recorded in A Classic of Acupuncture and Moxibustion (针灸甲乙经), are respectively the starting point of the YangqiaoChannel and the Yinqiao Channel, and they are two of the eight confluence points. Although records about the right-left compatible use of these two points can be found in documents, the same-side compatible use of them has never been heardabout. Inspired by the good therapeutic effects in the treatment of paralytic strabismus by means of the same-side compatible use of these two points1, the author has applied this compatible use of them in the treatment of craniofacial diseases and obtained obvious therapeutic effects. Some of the sample cases are reported in the following.
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文摘<strong>Objective:</strong> To investigate the therapeutic effect of Shenmai Injection on postoperative cerebral vasospasm in patients with ruptured aneurysms. <strong>Methods:</strong> Seventy patients undergoing craniotomy for ruptured aneurysms in our hospital were selected as study subjects and randomly divided into control (n = 33) and research (n = 37) groups, they were treated with nimodipine and nimodipine combined with Shenmai injection after operation. The blood flow velocity in the middle cerebral artery (MCA) before and at 1, 3, 7, 11 and 14 days after surgery and the incidence of cerebral vasospasm during these days were compared, and the GCS scores at 14 days postoperatively and GOS scores at 6 months postoperatively were compared between the two groups.<strong> Results:</strong> There were no statistically significant differences in the occurrence of cerebral vasospasm, GCS or GOS scores between the two groups (<em>P</em> > 0.05), but the period of postoperative cerebral vasospasm in the study group was significantly shorter than that in the control group. <strong>Conclusion:</strong> Shenmai injection has the effect of shortening the cycle of occurrence of cerebral vasospasm after the operation of ruptured aneurysms, promoting patients to recover as early as possible and reducing their physical and mental burden.
文摘Objective: To study the effect of Shenmai injection combined with irbesartan on the microinflammatory state and nutritional status of patients with peritoneal dialysis. Methods:A total of 108 patients with end-stage renal disease who received peritoneal dialysis in Guangyuan First People's Hospital between May 2014 and November 2016 were selected and randomly divided into two groups, the combined group received Shenmai injection combined with irbesartan therapy, and the ARB group received irbesartan therapy. The renal function indicators, inflammatory response indicators and nutritional status indicators of the two groups were detected before treatment as well as 3 months and 6 months after treatment. Results: Scr, BUN and RRF of both groups 3 months and 6 months after treatment were not significantly different from those before treatment;serum SAA, CRP, PAPP-A, CHE, TNF-α, IL-6 and IL-8 contents of both groups 3 months and 6 months after treatment were significantly lower than those before treatment, and serum SAA, CRP, PAPP-A, CHE, TNF-α, IL-6 and IL-8 contents of combined group 3 months and 6 months after treatment were significantly lower than those of ARB group;serum Alb, PA and Tf contents as well as mid-arm muscle circumference and mid-arm circumference of combined group 3 months and 6 months after treatment were not significantly different from those before treatment while serum Alb, PA and Tf contents as well as mid-arm muscle circumference and mid-arm circumference of control group 3 months and 6 months after treatment were significantly lower than those before treatment. Conclusion: Shenmai injection combined with irbesartan for peritoneal dialysis can reduce the microinflammatory state and improve the nutritional status.
文摘Background:To evaluate the efficacy and safety of the classic ancient prescription Shenmai injection(the classic ancient presciption)combined with Western medicine in the treatment of acute pancreatitis.Method:PubMed,the Cochrane Library,EMBASE,the Web of Science,China National Knowledge Infrastructure,Wanfang database,VIP Database and Chinese BioMedicine Literature Database were searched from database establishment to January 2021.After 2 researchers independently screened the literature,extracted data and evaluated the bias risk included in the study.A meta-analysis of randomized controlled trials of the classic ancient prescription Shenmai injection combined with Western medicine in the treatment of acute pancreatitis was conducted with the Revman 5.0 software.Result:A total of 19 randomized controlled trials were included,including 1,507 patients.The results of meta-analysis showed that the test group had advantage over the control group in total effective rate(RR=1.23,95%CI(1.17,1.34),P<0.00001),serum amylase level(stand mean difference=−2.92,95%CI(−3.75,−2.09),P<0.00001),C-reactive protein level and IL-6 level with statistically significant.Conclusion:The current evidence shows that the classic ancient prescription Shenmai injection combined with Western medicine can achieve better curative effect in the treatment of acute pancreatitis than using Western medicine alone.It has more advantages in terms of the total effective rate,reducing the level of serum amylase level and inflammatory cytokines.
文摘Objective: To explore effects of Shenmai Injection(参麦注射液) combined with Meglumine Adenosine Cyclophosphate Injection on cardiac function and peripheral serum levels of tumor necrosis factor-α(TNF-α), transforming growth factor-β1(TGF-β1) and interferon-γ(IFN-γ) in patients with viral myocarditis.Methods: A total of 70 patients with viral myocarditis admitted in Cardiovascular Medicine Department of our hospital from June 2016 to June 2018 were selected and divided into a control group(treated with Meglumine Adenosine Cyclophosphate Injection) and an observation group(additionally treated with Shenmai Injection(参麦注射液) on the treatment basis of the control group) according to random number method, with 35 cases in each group.Before and after the treatment, cardiac functional indexes like cardiac index(CI), left ventricular ejection fraction(LVEF) and left ventricular shortening fraction(FS), serum levels of TNF-α, TGF-β1 and IFN-γ, clinical efficacy and adverse reactions occurred in the 2 groups were recorded and compared.Results: Therapeutic effective rate in the observation group was 88.57%, higher than 68.57% in the control group(P < 0.05).After the treatment, cardiac functional indexes like CI, LVEF and FS were higher than those in the control group(P < 0.05).After the treatment, the serum expression levels of TNF-α and TGF-β1 were lower than those in the control group(P < 0.05), while the serum expression level of IFN-γ was higher than that in the control group(P < 0.05).There was no statistically significant difference in the adverse reaction rates between the 2 groups(P > 0.05).Conclusion: The treatment of patients with viral myocarditis by Shenmai Injection(参麦注射液) combined with Meglumine Adenosine Cyclophosphate Injection is more effective, reducing inflammation and restoring cardiac function.
基金supported by National Key Scientific Project for New Drug Discovery and Development of China (Grant no. 2009ZX09301-012)
文摘In this paper,the feasibility and advantages of employing high performance liquid chromatographic(HPLC) fingerprints combined with pattern recognition techniques for quality control of Shenmai injection were investigated and demonstrated.The Similarity Evaluation System was employed to evaluate the similarities of samples of Shenmai injection,and the HPLC generated chromatographic data were analyzed using hierarchical clustering analysis(HCA) and soft independent modeling of class analogy(SIMCA).Consistent results were obtained to show that the authentic samples and the blended samples were successfully classified by SIMCA,which could be applied to accurate discrimination and quality control of Shenmai injection.Furthermore,samples could also be grouped in accordance with manufacturers.Our results revealed that the developed method has potential perspective for the original discrimination and quality control of Shenmai injection.
基金Tianjin Science and Technology Committee (No. 98113411)
文摘Objective: To evaluate the dynamic change of Th1/Th2 cytokines in serum, peritoneal lavage fluid (PLF) and splenic macrophages (SM) in rats with severe peritonitis, and to observe the therapeutic effects of recombinant interleukin-12 (rIL-2) and Shenmai injection (SMI, 参麦注射液), a Chinese medicinal preparation.Methods: Severe peritonitis (SP) model was induced by intraperitoneal injection of E. coli and B. frag, and mild peritonitis (MP) model was induced by cecal ligation and punching. Then the following experiments were done: (1) Survival rates of animals after every 6 hrs in the 72 hrs after modeling were recorded, serum and PLF levels of cytokines, including tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), and interleukin-10 (IL-10), 6 hrs, 12 hrs, 24 hrs and 48 hrs after modeling were measured. (2) Model rats were treated with rIL-12 or SMI, the survival rate was recorded and serum levels of TNF-α, INF-γ, and IL-10 before and after treatment were measured, and (3) amount of these cytokines produced by SM were determined 6 hrs, 12 hrs and 24 hrs after treatment. The survival rates and levels of cytokines were then compared between the groups (model group treated with rIL-12 or SMI, untreated model group, and blank group).Results: Serum and PLF levels of IFN-γ, TNF-α at all the time points in SP rats were significantly lower than those in MP rats while those of IL-10 6 hrs and 12 hrs after modeling were significantly higher in the former than that in the latter (P<0.05). IFN-γ secretion of SM in SP rats was significantly higher than that in MP rats 6 hrs after modeling (P<0.05). Administration of rlL-12 or SMI given before modeling could improve the survival rate of the model rats (P<0.05) and cause significant increase of the serum level and SM secretion of IFN-γ. Conclusion: Imbalance in promoting/antagonizing inflammatory cytokines and Th2 response dominance appear in SP rats early at the initiating stage, and SM secretion of inflammation promoting factor also reduces. Administration in time of rIL-12 and SMI, may increase the survival rate, and its mechanism may be related with their immuno-stimulating action.
基金Supported by Hunan Provincial Natural Science Foundation of China(No.2020JJ5408)Scientific Research Fund of Hunan Provincial Education Department(No.21B0361)+1 种基金Research Fund of Hunan University of Chinese Medicine(No.2019XJJJ012)Zhuzhou Second Batch of Science and Technology Guidance Projects(No.2017-17)。
文摘Objective: To study effects of Shenmai Injection on hypertensive heart failure and its mechanism for inhibiting myocardial fibrosis. Methods: Salt-sensitive(Dahl/SS) rats were fed with normal diet(0.3% Na Cl) and the high-salt diet(8% Na Cl) to observe the changes in blood pressure and heart function, as the control group and the model group. Salt-insensitive rats(SS-13BN) were fed with the high-salt diet(8% Na Cl) as the negative control group. After modeling, the model rats were randomly divided into heart failure(HF) group, Shenmai Injection(SMI) group and pirfenidone(PFD) group by a random number table, with 6 rats in each group. They were given sterilized water, SMI and pirfenidone, respectively. Blood pressure, cardiac function, fibrosis and related molecular expression were detected by sphygmomanometer, echocardiogram, enzyme linked immunosorbent assay(ELISA),hematoxylin-eosin staining, Masson staining, immunofluorescence and qPCR analysis. Results: After high-salt feeding, compared with the control and negative control group, in the model group the blood pressure increased significantly, the left ventricular ejection fraction(LVEF) and left ventricular fraction shortening(LVFS) were significantly reduced, and the serum NT-pro BNP concentration increased significantly(all P<0.05);furthermore,the arrangement of myocardial cells was disordered, the edema was severe, and the degree of myocardial fibrosis was also significantly increased(P<0.05);the protein and m RNA expressions of collagen type Ⅰ(Col Ⅰ) were up-regulated(P<0.05), and the mRNA expressions of transforming growth factor β1(TGF-β1), Smad2 and Smad3 were significantly up-regulated(P<0.05). Compared with HF group, after intervention of Shenmai Injection, LVEF and LVFS increased, myocardial morphology was improved, collagen volume fraction decreased significantly(P<0.05), and the mRNA expressions of Col Ⅰ, TGF-β1, Smad2 and Smad3, as well as Col Ⅰprotein expression, were all significantly down-regulated(all P<0.05). Conclusion: Myocardial fibrosis is the main pathological manifestation of hypertensive heart failure, and Shenmai Injection could inhibit myocardial fibrosis and effectively improve heart failure by regulating TGF-β1/Smad signaling pathway.
文摘目的对参麦注射液应用于慢性阻塞性肺疾病(COPD)伴呼吸衰竭的有效性及安全性进行Meta分析。方法检索中国知网、万方数据库、维普资讯、中国生物医学文献数据库、PubMed、Cochrane Library、Web of Science、Embase医学文献数据库,由2位研究者根据纳入、排除标准独立筛选文献,提取相应研究信息并交叉核对,筛选出参麦注射液治疗COPD伴呼吸衰竭的随机对照试验,使用RevMan5.4软件对纳入研究进行Meta分析,并使用GRADE评价系统对结局指标质量进行分级。结果本研究纳入16项临床研究,共1313例患者,观察组667例,对照组646例;参麦注射液联合西医常规治疗COPD伴呼吸衰竭患者,在临床总有效率[OR=3.10,95%CI(2.05~4.70),P<0.00001]、氧分压[MD=7.98,95%CI(4.97~11.00),P<0.00001]、二氧化碳分压[MD=-8.31,95%CI(-11.11~-5.51),P<0.00001]、C反应蛋白(CRP)[SMD=-1.64,95%CI(-2.37~-0.91),P<0.00001]、第一秒用力呼气容积(FEV1)[MD=0.38,95%CI(0.33~0.42),P<0.00001]方面,相较对照组差异有统计学意义(P<0.01);用力肺活量(FVC)两组间差异无统计学意义(P>0.05)。GRADE证据分级结果提示,总有效率、动脉血气氧分压、动脉血气二氧化碳分压、CRP、FVC、FEV1为极低级质量证据。结论西医常规结合参麦注射液治疗COPD合并呼吸衰竭可以提高临床治疗总有效率,改善低氧血症和(或)二氧化碳潴留,减轻炎症,安全性较好。
基金supported by the China National Nature Science Foundation(81573496,81773989,81530098 and 81573494)National Research Council of Science and Technology Major Project of China(2017ZX09201004-019 and 2019ZX09721001006-005)+6 种基金International Science and Technology Center Program of China(2017YFE0109600)Foundation for Innovative Research Groups of the National Natural Science Foundation of China(No.81421005)Jiangsu Province Nature Science Foundation(No.BK20160076,China)Jiangsu Province“333”project,ChinaSix talent peaks project in Jiangsu Province(YY-060),ChinaNational Basic Research Program of China(973 Program,No.2017YFA0205400)“Double First-Class”University project(CPU2018GF01,China)
文摘Shenmai injection(SMI)is a well-defined herbal preparation that is widely and clinically used as an adjuvant therapy for cancer.Previously,we found that SMI synergistically enhanced the activity of chemotherapy on colorectal cancer by promoting the distribution of drugs in xenograft tumors.However,the underlying mechanisms and bioactive constituents remained unknown.In the present work,the regulatory effects of SMI on tumor vasculature were determined,and the potential anti-angiogenic components targeting tumor endothelial cells(TECs)were identified.Multidimensional pharmacokinetic profiles of ginsenosides in plasma,subcutaneous tumors,and TECs were investigated.The results showed that the concentrations of protopanaxadiol-type(PPD)ginsenosides(Rb1,Rb2/Rb3,Rc,and Rd)in both plasma and tumors,were higher than those of protopanaxatriol-type(Rg1 and Re)and oleanane-type(Ro)ginsenosides.Among PPD-type ginsenosides,Rd exhibited the greatest concentrations in tumors and TECs after repeated injection.In vivo bioactivity results showed that Rd suppressed neovascularization in tumors,normalized the structure of tumor vessels,and improved the anti-tumor effect of 5-fluorouracil(5 FU)in xenograft mice.Furthermore,Rd inhibited the migration and tube formation capacity of endothelial cells in vitro.In conclusion,Rd may be an important active form to exert the anti-angiogenic effect on tumor after SMI treatment.
基金Supported by the National Natural Science Foundation of China(No.81970722)。
文摘Objective:To examine the effect of Shenmai Injection(SMJ)on ferroptosis during myocardial ischemia reperfusion(I/R)injury in rats and the underlying mechanism.Methods:A total of 120SPF-grade adult male SD rats,weighing 220–250 g were randomly divided into different groups according to a random number table.Myocardial I/R model was established by occluding the left anterior descending artery for 30 min followed by 120 min of reperfusion.SMJ was injected intraperitoneally at the onset of 120 min of reperfusion,and erastin(an agonist of ferroptosis),ferrostatin-1(Fer-1,an inhibitor of ferroptosis)and ML385(an inhibitor of nuclear factor erythroid-2 related factor 2(Nrf2))were administered intraperitoneally separately 30 min before myocardial ischemia as different pretreatments.Cardiac function before ischemia,after ischemia and after reperfusion was analysed.Pathological changes in the myocardium and the ultrastructure of cardiomyocytes were observed,and the myocardial infarction area was measured.Additionally,the concentration of Fein heart tissues and the levels of creatine kinase-MB(CK-MB),troponin I(cTnI),malondialdehyde(MDA)and superoxide dismutase(SOD)in serum were measured using assay kits,and the expressions of Nrf2,glutathione peroxidase 4(GPX4)and acyl-CoA synthetase long-chain family member 4(ACSL4)were examined by Western blot.Results:Compared with the sham group,I/R significantly injured heart tissues,as evidenced by the disordered,ruptured and oedematous myocardial fibres;the increases in infarct size,serum CK-MB,cTnI and MDA levels,and myocardial Feconcentrations;and the decreases in SOD activity(P<0.05).These results were accompanied by ultrastructural alterations to the mitochondria,increased expression of ACSL4 and inhibited the activation of Nrf2/GPX4 signalling(P<0.05).Compared with the I/R group,pretreatment with 9 mL/kg SMJ and 2 mg/kg Fer-1 significantly reduced myocardial I/R injury,Feconcentrations and ACSL4 expression and attenuated mitochondrial impairment,while 14 mg/kg erastin exacerbated myocardial I/R injury(P<0.05).In addition,cardioprotection provided by 9 mL/kg SMJ was completely reversed by ML385,as evidenced by the increased myocardial infarct size,CK-MB,cTnI,MDA and Feconcentrations,and the decreased SOD activity(P<0.05).Conclusions:Ferroptosis is involved in myocardial I/R injury.Pretreatment with SMJ alleviated myocardial I/R injury by activating Nrf2/GPX4 signalling-mediated ferroptosis,thereby providing a strategy for the prevention and treatment of ischemic heart diseases.
