Neuroprotective effects of Ginkgo biloba dropping pills in Parkinson's disease

Parkinson's disease(PD) is the second most common neurodegenerative disease in the world;however,it lacks effective and safe treatments. Ginkgo biloba dropping pill(GBDP), a unique Chinese G. biloba leaf extract preparation, exhibits antioxidant and neuroprotective effects and has a potential as an alternative therapy for PD. Thus, the aims of this study were to evaluate the effects of GBDP in in vitro and in vivo PD models and to compare the chemical constituents and pharmacological activities of GBDP and the G. biloba extract EGb 761. Using liquid chromatography tandem-mass spectrometry, 46 GBDP constituents were identified. Principal component analysis identified differences in the chemical profiles of GBDP and EGb 761. A quantitative analysis of 12 constituents showed that GBDP had higher levels of several flavonoids and terpene trilactones than EGb 761, whereas EGb 761 had higher levels of organic acids.Moreover, we found that GBDP prevented 6-hydroxydopamine-induced dopaminergic neuron loss in zebrafish and improved cognitive impairment and neuronal damage in methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced PD mice. Although similar effects were observed after EGb 761 treatment,the neuroprotective effects were greater after GBDP treatment on several endpoints. In addition, in vitro results suggested that the Akt/GSK3β pathway may be involved in the neuroprotective effects of GBDP.These findings demonstrated that GBDP have potential neuroprotective effects in the treatment of PD.

Protective effect of gingerol dropping pills against alcoholic liver injury in mice

OBJECTIVE To prepare gingerol dropping pills and to investigate its protective effect on alcoholic liver injury. METHODS The prescription was selected by orthogonal design method and the effect of the option and ratio of ground substance,the temperature of drug. The hardness,circular degree,the tail formation and the dissolution time were studied. Totally 40 KM mice were randomly divided into control group,model group,gingerol dropping pill group(400 mg·kg^(-1)·d^(-1)) and positive control group(bifendate,150 mg·kg^(-1)·d^(-1)) of 10 mice each. The mice from the model and two drug groups were administrated with liqueur[0.15 mL/(10 g·d)]daily by gavage for 3 weeks,Two hours later,drug group mice were treated corresponding gingerol dropping pill and bifendate. Meanwhile,the control group were gavaged same amount of normal saline. Finally,when the model of acute alcoholic liver injury was established on the 22 stday,Biochemical indicators of ocular blood in mice were observed.We also observed the change of liver morphology. RESULTS Under optimum conditions,we can obtain dropping pills having circular shape,touching with hardness and short dissolution time. Compared with the control group,the levels of alanine transaminase(ALT),glutamic-oxaloacetic transaminase(AST) and malondialdehyde(MDA) in model group were obviously increased(P<0.01),While the activity of Superoxide dismutase(SOD) were decreased. In addition,In model group,mice liver disorders,hepatic lobule fusion,accompanying a large number of patchy sample liver cell vacuoles,various sizes of fat vacuoles appeared in cytoplasm and inflammatory cell infiltration were visible around the central vein. On the contrary,compared with the model group,drug groups attenuated or even reversed hepatic pathological changes. Form gingerol dropping pill group,an increase in hepatic SOD activity and serum ALT and AST activities were found and a significant decrease in hepatic MDA content were also observed(P<0.01). CONCLUSION The prescription of gingerol dropping pills was reasonable,and the preparation process was simple. Gingerol dropping pills can protect liver from alcoholic liver injury to some extend,and the mechanism may be related to its antioxidant effect.

A theoretical study of miRNA155-DNA methylation mediated mitokATP regulating mitochondrial autophagy in the improvement of myocardial ischemia-reperfusion injury by Qishen Yiqi Dropping Pills

In the state of acute myocardial ischemia,miRNA expression can regulate related genes and proteins,reduce myocardial cell damage,and thus play a protective role in the myocardium.However,the specific mechanism still needs to be further explored.Recent studies have found that the opening of the mitoKATP channel can regulate mitochondrial autophagy,and the initiation of miRNA-DNA methylation plays a regulatory role in inducing cell autophagy.The applicant research team previously found that Qishen Yiqi Dropping Pills could significantly improve myocardial ischemia by mediating MitokATP channels to regulate mitochondrial autophagy.,and animal experiments have confirmed that miR-155 plays a significant role in the aspect of autophagy regulates,inflammatory reaction and Vascular smooth muscle cell migration.Therefore,the applicant innovatively proposed that Qishen Yiqi Dropping Pills can regulate miRNA155-DNA methylation to mediate the opening of mitoKATP,thereby regulating mitochondrial autophagy and improving myocardial ischemia.In this paper,the association between mitochondrial autophagy and oxidative stress injury after myocardial ischemia was described,and the possible mechanism of Qisen Yiqi dropping pills regulating mitochondrial autophagy by regulating miRNA155-DNA methylation to mediate MitokATP to improve myocardial ischemia reperfusion injury was discussed,so as to provide theoretical ideas for related research.

The Effect of Ginkgo Biloba Leaf Dropping Pill Combined with Butylphthalide Capsule on Cognitive Dysfunction in Patients after Acute Ischemic Stroke and Its Impact on Serum Cytokines

Objective: To investigate the therapeutic effect of Ginkgo biloba extract dropping pills combined with butylphthalide capsules on cognitive dysfunction in patients after acute ischemic stroke (AIS) and its impact on serum cytokines CRP, IL-6, and Hcy. Methods: This study selected 76 patients with cognitive dysfunction after ischemic stroke who were hospitalized at Zhuji People’s Hospital from January 2023 to January 2024. The patients were divided into two groups. The control group was treated with butylphthalide capsules, while the combination group received Ginkgo biloba extract dropping pills in addition to the treatment given to the control group. The neurological function, cognitive function, activities of daily living, and levels of serum cytokines CRP, IL-6, and Hcy were compared between the two groups after 1 month and 3 months of treatment. Results: The NIHSS scores, MMSE scores, ADL scores, and levels of CRP, IL-6, and Hcy in both groups showed statistically significant differences compared to before treatment (P Conclusion: The combination of Ginkgo biloba extract dropping pills and butylphthalide capsules has a better therapeutic effect on cognitive dysfunction in patients after ischemic stroke. It can improve the neurological function and cognitive function of patients, enhance their ability to perform daily activities, and reduce inflammatory responses.

Effect of Shexiang Tongxin Dropping Pills(麝香通心滴丸) on the Immediate Blood Flow of Patients with Coronary Slow Flow

Objective: To observe the immediate effect and safety of Shexiang Tongxin dropping pills(麝香通心滴丸, STDP) on patients with coronary slow flow(CSF), and furthermore, to explore new evidence for the use of Chinese medicine in treating ischemic chest pain. Methods: Coronary angiography(CAG) with corrected thrombolysis in myocardial infarction(TIMI) frame count(CTFC) was applied(collected at 30 frames/s). The treatment group included 22 CSF patients, while the control group included 22 individuals with normal coronary?ow. CSF patients were given 4 STDP through sublingual administration, and CAG was performed 5 min after the medication. The immediate blood ?ow frame count, blood pressure, and heart rate of patients before and after the use of STDP were compared. The liver and kidney functions of patients were examined before and after treatments. Results: There was a signi?cant difference in CTFC between groups(P<0.05). The average CTFC values of the vessels with slow blood ?ow in CSF patients were, respectively, 49.98±10.01 and 40.42±11.33 before and after the treatment with STDP, a 19.13% improvement. The CTFC values(frame/s) measured before and after treatment at the left anterior descending coronary artery, left circumflex artery, and right coronary artery were, respectively, 48.00±13.32 and 41.80±15.38, 59.00±4.69 and 50.00±9.04, and 51.90±8.40 and40.09±10.46, giving 12.92%, 15.25%, and 22.76% improvements, respectively. The CTFC values of vessels with slow ?ow before treatment were signi?cantly decreased after treatment(P<0.05). There were no apparent changes in the heart rate, blood pressure, or liver or kidney function of CSF patients after treatment with STDP(all P>0.05). Conclusions: The immediate effect of STDP in treating CSF patients was apparent. This medication could signi?cantly improve coronary ?ow without affecting blood pressure or heart rate. Our ?ndings support the potential of Chinese medicine to treat ischemic chest pain.

Improved stability and oral bioavailability of Ganneng dropping pills following transforming lignans of herpeto- spermum caudigerum into nanosuspensions

The present study was designed to improve storage stability and oral bioavailability of Ganneng dropping pills(GNDP) by transforming lignans of Herpetospermum caudigerum(HL) composed of herpetrione(HPE) and herpetin(HPN) into nanosuspension(HL-NS), the main active ingredient of GNDP, HL-NS was prepared by high pressure homogenization and lyophilized to transform into solid nanoparticles(HL nanoparticles), and then the formulated HL nanoparticles were perfused into matrix to obtain NS-GNDP by melting method. For a period of 3 months, the content uniformity, storage stability and pharmacokinetics test in vivo of NS-GNDP were evaluated and compared with regular GNDP at room temperature. The results demonstrated that uniformity of dosage units of NS-GNDP was acceptable according to the criteria of Chinese Pharmacopoeia 2015 J. Physical stability of NS-GNDP was investigated systemically using photon correlation spectroscopy(PCS), zeta potential measurement, and scanning electron microscopy(SEM). There was a slight increase in particles and PI of HL-NS re-dispersed from NS-GNDP after storage for 3 months, compared with new formulated NS-GNDP, which indicated a good redispersibility of the NS-GNDP containing HL-NS after storage. Besides, chemical stability of NS-GNDP was studied and the results revealed that HPE and HPN degradation was less when compared with that of GNDP, providing more than 99% of drug residue after storage for 3 months. In the dissolution test in vitro, NS-GNDP remarkably exhibited an increased dissolution velocity compared with GNDP and no distinct dissolution difference existed within 3 months. The pharmacokinetic study showed that HPE and HPN in NS-GNDP exhibited a significant increase in AUC0–t, Cmax and decrease in Tmax when compared with regular GNDP. These results indicated that NS-GNDP possessed superiority with improved storage stability and increased dissolution rate and oral bioavailability.

Induction of Angiogenesis and Neurogenesis by Serum from Rats Treated with Shunaoxin Dropping Pills

Objective Shunaoxin Dropping Pills(SDPs),a Chinese patent medicine,has been used widely in China for the treatment of headache,amnesia,and insomnia.The aim of the present study is to observe the effect of SDPs on inducing angiogenesis and neurogenesis in vitro.Methods The present testing system using the serum obtained from animals ig treated with SDPs and a co-culture system in vitro was used to investigate if SDPs promotes brain microvascular endothelial cells(BMECs)tube formation and neural differentiation of neural stem/progenitor cells(NSPCs),which plays important roles in angiogenesis and neurogenesis.Results The SDPs serum sampled from rats ig treated with SDPs for 3 d dose-dependently promoted the tube like structure formation of cultured BMECs,and enhanced the fraction of MAP-2 positive cells of NSPCs,which co-cultured with the BMECs and astrocyte.In addition,there was no significant change in the percentage of glial fibrillary acidic protein positive cells.Conclusion Our results show that SDPs serum can induce neural differentiation and BMECs tube formation in vitro.

Effects of Qishen Yiqi dripping pills-containing serum on KATP channel opening and PI3K/AKT signaling pathway in hypoxic/reoxygenated H9C2 cardiocytes

Objective:To investigate the effects of Qishen Yiqi dropping pills serum on KATP channel opening and PI3K/AKT signaling pathway of hypoxic/reoxygenated H9C2 cardiocytes.Methods:H9C2 cardiocytes cultured in vitro were randomly divided into five groups,A:H9C2 cell group B:H9C2 cells+H2O2 model group C:H9C2 cells+H2O2 model+Qishen Yiqi group D:H9C2 cells+H2O2 model+Qishen Yiqi+wort group E:H9C2 cells+H2O2 model+Qishenyiqi+5-HD group,the drug intervention is according to the corresponding conditions.CCK-8 method was used to detect the cell activity of each group;Western blot was used to detect the expression of AKT and P-Akt proteins in myocardial cells in each group.The current was recorded by the standard patch clamp whole cell recording method,and the current was collected and analyzed by Pclamp6.0 software.Results:CCK-8 test results showed that compared with group A,the activity of myocardial cells in group B was significantly decreased,and the difference was statistically significant(P<0.01);compared with group B,the difference in group C was statistically significant(P<0.01);compared with C,cardiomyocyte activity in D and E group were significantly decreased,and the difference was statistically significant(P<0.05);WB results showed that compared with A,p-Akt protein expression in B,C,D and E groups were significantly decreased,and the difference was statistically significant(P<0.01);compared with group B,p-Akt protein expression in C,D and E group were significantly increased,and the difference was statistically significant(P<0.01),but there was no significant difference in AKT expression among groups(P>0.05);The results of whole cell patch clamp experiment showed that the outward current of B was significantly increased compared with that of A,and the difference between groups was statistically significant(P<0.01);compared with group B,cardiomyocytes in group C further increased the outward current,and the difference between groups was statistically significant(P<0.01);compared with C,the current of D and E group were significantly decreased,with statistical significance between groups(P<0.01).Conclusion:QishenYiqi dropping pills can protect cardiomyocytes by activating p-Akt protein expression and KATP channel opening in H9C2 cardiomyocytes.

Shexiang Tongxin Dropping Pill Promotes Angiogenesis through VEGF/eNOS Signaling Pathway on Diabetic Coronary Microcirculation Dysfunction

Objective:To study the effect of Shexiang Tongxin Dropping Pill(STDP)on angiogenesis in diabetic cardiomyopathy mice with coronary microcirculation dysfunction(CMD).Methods:According to a random number table,6 of 36 SPF male C57BL/6 mice were randomly selected as the control group,and the remaining 30 mice were injected with streptozotocin intraperitoneally to replicate the type 1 diabetes model.Mice successfully copied the diabetes model were randomly divided into the model group,STDP low-dose group[15 mg/(kg·d)],medium-dose group[30 mg/(kg·d)],high-dose group[60 mg/(kg·d)],and nicorandil group[15 mg/(kg·d)],6 in each group.The drug was given by continuous gavage for 12 weeks.The cardiac function of mice in each group was detected at the end of the experiment,and coronary flow reserve(CFR)was detected by chest Doppler technique.Pathological changes of myocardium were observed by hematoxylin-eosin staining,collagen fiber deposition was detected by masson staining,the number of myocardial capillaries was detected by platelet endothelial cell adhesion molecule-1 staining,and the degree of myocardial hypertrophy was detected by wheat germ agglutinin staining.The expression of the vascular endothlial growth factor(VEGF)/endothelial nitric oxide synthase(eNOS)signaling pathway-related proteins in myocardial tissue was detected by Western blot.Results:Compared with the model group,medium-and high-dose STDP significantly increased the left ventricular ejection fraction and left ventricular fraction shortening(P<0.01),obviously repaired the disordered cardiac muscle structure,reduced myocardial fibrosis,reduced myocardial cell area,increased capillary density,and increased CFR level(all P<0.01).Western blot showed that high-dose STDP could significantly increase the expression of VEGF and promote the phosphorylation of vascular endothelial growth factor receptor 2,phosphoinositide 3-kinase,protein kinase B,and eNOS(P<0.05 or P<0.01).Conclusion:STDP has a definite therapeutic effect on diabetic CMD,and its mechanism may be related to promoting angiogenesis through the VEGF/eNOS signaling pathway.

Meta-analysis of the clinical efficacy of Liqi Huoxue drop pill in the treatment of angina pectoris in coronary artery disease

Objective:To evaluate the efficacy of Liqi Huoxue dropping pills in the treatment of angina pectoris in coronary heart disease using the Meta-analysis system.Methods:Randomized controlled trials(RCT)on the treatment of angina pectoris in coronary artery disease with the combination of Western medicine with Liqi Huoxue drop pills were searched using computerized search databases,including English databases PubMed,Embase,Web of Science,The Cochrane Library and Chinese databases CNKI,VIP,WanFang Data and CBM from the time of establishment until February 1,2022.Data extraction was performed independently by two investigators and the quality of the literature of the included studies was assessed.A meta-analysis of the included literature was performed using Revman 5.4 software.Results:Nine studies with a total of 982 patients were included.The results of Meta-analysis showed that the observation group,which adopted conventional treatment of Western medicine combined with Li qi huo xue dropping pills,was better than the control group,which was treated with conventional Western medicine alone.Clinical efficacy of the intervention group[R R=1.20,95%CI=(1.12,1.29),P<0.00001],Angina pectoris symptom treatment[RR=1.17,95%CI=(1.07,1.29),P=0.0010],Number of angina attacks[SMD=-2.26,95%CI(-4.10,-0.42),P=0.002],IL-6[MD=-4.65,95%CI(-6.91,-2.39),P<0.0001],IL-18[MD=-2.53,95%CI(-2.84,-2.22),P<0.00001],HS-CRP[MD=-0.08,95%CI(-1.81,-0.75),P<0.00001],and NO[M D=8.03,95%CI(0.93,15.14),P=0.03]were significantly different and better than the control group(western conventional treatment),and the differences were all statistically significant.Conclusion:Combining Liqi Huoxue drop pill with conventional Western medicine for patients with coronary angina can effectively improve the clinical efficacy,the efficacy of angina symptoms,the number of angina attacks,serum inflammatory indexes interleukin-6,interleukin-18,high-sensitivity C-reactive protein,and endothelial function NO indexes in patients with coronary angina,providing a reliable evidence-based basis for combining Liqi Huoxue drop pill with Western medicine for the treatment of coronary angina.

Efficacy of Rabdosia Rubescens in the Treatment of Gingivitis

This study evaluated the efficacy ofrabdosia rubescens against gingivitis and compared the therapeutic efficacy of different dosage forms of rabdosia rubescens. A multi-center, randomized, double-blind, double-simulation, positive-controlled and parallel trial was conducted. A total of 136 patients exhibiting clinical symptoms of gingivitis were enrolled. The subjects were randomly assigned to two groups： test group （n=67）, in which rabdosia rubescens drop pill （960 mg） and 4 tablets of simulation agent of rabdosia rubescen were orally given to the subjects three times a day for 5 days; and control group （n=69）, in which the subjects were administered the tablets of rabdosia rubescens （1000 mg） and 24 drop pills of simulation agent of rabdosia rubescens thrice daily for 5 days. The experimental protocols and diagnostic criteria were established by expert panel prior to the experiment. The clinical symptoms were graded according to the severity of the disease and quantified. The total scores and scores for each clinical symptom of gingivitis were assessed at baseline and on the 6th day post-treatment. The therapeutic efficacy was compared between the two groups and in each group itself before and after the treatment. The results showed that in the two groups, the subjects who were given rabdosia rubescens, drop pill or tablet, had a decrease in total scores and scores for each clinical symptom when compared with those before treatment （P〈0.01）. There was significant difference in the therapeutic efficacy between the test group and the control group with the efficacy rate being 92.54% and 79.71% respectively （P〈0.05）. It was concluded that rabdosia rubescens showed great promise in treating gingivitis. And rabdosia rubescens drop pill was more efficacious than rabdosia rubescens tablet.

Shexiang Tongxin Dropping Pill Allieviates Heart Failure via Extracellula Matrix-Receptor Interaction Pathways Based on RNA-Seq Transcriptomics and Experimental Studies

Objective:To investigate the protective mechanisms of Chinese medicine Shexiang Tongxin Dropping Pills(STDP) on heart failure(HF).Methods:Isoproterenol(ISO)-induced HF rat model and angiotensin Ⅱ(Ang Ⅱ)-induced neonatal rat cardiac fibroblast(CFs) model were used in the present study.HF rats were treated with and without STDP(3 g/kg).RNA-seq was performed to identify differentially expressed genes(DEGs).Cardiac function was evaluated by echocardiography.Hematoxylin and eosin and Masson’s stainings were taken to assess cardiac fibrosis.The levels of collagen Ⅰ(Col Ⅰ) and collagen Ⅲ(Col Ⅲ) were detected by immunohistochemical staining.CCK8 kit and transwell assay were implemented to test the CFs’ proliferative and migratory activity,respectively.The protein expressions of α-smooth muscle actin(α-SMA),matrix metalloproteinase-2(MMP-2),MMP-9,Col I,and Col Ⅲ were detected by Western blotting.Results:The results of RNA-seq analysis showed that STDP exerted its pharmacological effects on HF via multiple signaling pathways,such as the extracellular matrix(ECM)-receptor interaction,cell cycle,and B cell receptor interaction.Results from in vivo experiments demonstrated that STDP treatment reversed declines in cardiac function,inhibiting myocardial fibrosis,and reversing increases in Col Ⅰ and Col Ⅱ expression levels in the hearts of HF rats.Moreover,STDP(6,9 mg/mL) inhibited the proliferation and migration of CFs exposed to Ang Ⅱin vitro(P<0.05).The activation of collagen synthesis and myofibroblast generation were markedly suppressed by STDP,also the synthesis of MMP-2 and MMR-9,as well as ECM components Col Ⅰ,Col Ⅲ,and α-SMA were decreased in Ang Ⅱ-induced neonatal rats’ CFs.Conclusions:STDP had anti-fibrotic effects in HF,which might be caused by the modulation of ECM-receptor interaction pathways.Through the management of cardiac fibrosis,STOP may be a compelling candidate for improving prognosis of HF.

Hippocampal CA1 pyramidal cells and neurotrophic factors in a rat model of vascular dementia following Xiongma drop pill versus Ginkgo leaf tablets

BACKGROUND： Previous studies have demonstrated the neuroprotective effects of Xiongma drop pill （XMDP） in a mouse model of vascular dementia. Neurotrophic factors play an important role in repair and regeneration of injured neurons. OBJECTIVE： To compare the effects of XMDP and Ginkgo leaf tablets on the appearance and number of hippocampal CA1 pyramidal neurons, as well as neurotrophic factor content in brain tissues, during vascular dementia formation to explore the neuroprotective mechanisms of XMDP. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the Laboratory of Pharmacology, College of Pharmacy, Harbin University of Commerce between April 2007 and December 2008. MATERIALS： XMDP was prepared by the College of Pharmacy, Harbin University of Commerce, with each 40 mg pill containing ferulic acid （≥ 0.149 mg） and gastrodin （≥ 0.171 mg）. Ginkgo leaf tablets were purchased from Taiyuan Qianyuan Pharmacy, China. METHODS： Healthy, adult, male, Wistar rats were randomly assigned to 6 groups： sham-operation, model, XMDP （high-, middle-, and low- dose）, and Ginkgo leaf tablets. The 6 groups were subdivided into two subgroups according to administration days, i.e., 30 and 60 days, with 8 animals in each subgroup. Rats in the model, XMDP, and Ginkgo leaf tablets groups were subjected to permanent bilateral ligation of the common carotid artery to establish a vascular dementia model. At 8 days after model establishment, all groups received intragastric administration once daily of the following： 10 mL/kg normal saline in the sham-operation and model groups; 0.4, 0.2, and 0.1 g/kg XMDP in the high-, middle-, and low-dose XMDP groups, respectively; and 50 mg/kg Ginkgo leaf tablets in the Ginkgo leaf tablets group. MAIN OUTCOME MEASURES： Hematoxylin-eosin staining was used to observe appearance and to quantify the number of hippocampal CA1 pyramidal neurons. Brain-derived neurotrophic factor and nerve growth factor concentrations in brain tissues were detected by enzyme-linked immunosorbent assay. RESULTS： Following model establishment, hippocampal CA1 neurons exhibited pathological changes. Compared with the sham-operation group, the number of pyramidal neurons significantly decreased （P 〈 0.05 or P 〈 0.01）, and neurotrophic factor concentration increased in the model rats （P 〈 0.05 or P 〈 0.01）. XMDP attenuated neuronal injury in a dose-dependent manner： the number of pyramidal neurons and neurotrophic factor concentrations were significantly increased compared with the model group （P〈 0.05 or P〈 0.01）. High- and middle-dose XMDP resulted in equivalent effects to Ginkgo leaf tablets. In addition, neurotrophic factor concentrations in all XMDP groups, after 60 days of administration, were remarkably greater than corresponding concentrations at 30 days （P 〈 0.05 or P 〈 0.01 ）. CONCLUSION： Hippocampal CA1 pyramidal cells exhibited pathological injury following establishment of the vascular dementia model. Middle- and high-dose XMDP increased neurotrophic factor expression in the brain of vascular dementia rats, which suggested neuroprotection equivalent to Ginkgo leaf tablets.

Experimental study of qishen yiqi drop pill combined with bone marrow mesenchymal stem cell transplantation on angiogenesis and cardiac function in mice with myocardial infarction

Objective:To investigate the effects ofQishengyiqi drop pill combined with bone marrow mesenchymal stem cell transplantation on angiogenesis and cardiac function in mice after myocardial infarction through in vitro cell molecular biology experiments.Methods:The animals used in this experiment were male mice with eGFP+/-.Sixty mice were randomly divided into three groups(n=20):myocardial infarction group(MI+PBS),myocardial infarction+mesenchyme plasma stem cell transplantation group(MI+MSCs)and myocardial infarction+Qishenyiqi drip pill combined with mesenchymal stem cell transplantation group(MI+MSCs+QSYQ).Qishenyiqi dripping pills were prepared into a medicinal solution with a concentration of 3.9 mg/mL with distilled water.The MI+MSCs+QSYQ group was orally administered with 0.1 mL/kg/day,and the other two groups were orally administered with an equal amount of normal saline.Mice in each group were adaptively fed continuously for 2 weeks,and the myocardial infarction model was established by ligation of the anterior descending coronary artery by thoracic ligation.Twenty-four hours after the model was established,bone marrow mesenchymal stem cells were isolated from the tibia of the mice and injected intracardiacly Bone marrow-derived mesenchymal stem cells were transplanted,and multiple injections were made around the myocardial infarction area of mice.The control group was injected with the same amount of PBS.0h,3 days,7 days,and 14 days after cell transplantation,observe the stem cell morphology under a microscope;on day 7 of cell transplantation,track the expression of eGFP-positive cells with a fluorescence microscope;before modeling,14 and 21 days after cell transplantation,use Cardiac function was measured by echocardiography.After 21 days of modeling,the mice were sacrificed,and heart samples were taken.The angiogenesis of the mice was observed by immunohistochemical staining and microvascular density determination.Results:The morphological growth of transplanted stem cells was proportional to the time of cell transplantation.Compared with MI+PBS group,CD90.2 and y6A were highly expressed on the surface of bone marrow mesenchymal stem cells in MI+MSCs group and MI+MSCs+QSYQ group,while CD31 and CD117 were almost not expressed.On the 21st day after stem cell transplantation,the values of LVDd and LVSD in MI+MSCs+QSYQ group were significantly lower than those in MI+PBS group and MI+MSCs group.At the same time,LVEF and LVFS increased significantly.The results of quantitative immunohistochemical analysis showed that the angiogenesis density in the MI+MSCs+QSYQ group increased significantly,and the difference between the groups was statistically significant(P<0.05).Conclusion:Qishen Yiqi dripping pills combined with bone marrow mesenchymal stem cell transplantation can not only promote angiogenesis in mice with myocardial infarction,but also play a positive role in improving cardiac function.

Rapid Analysis and Identification of Absorbed Components and Their Metabolites of Yuanhu Zhitong Dropping Pill in Rat Plasma and Brain Tissue Using UPLC-Q-TOF/MS with Multivariate Statistical Analysis

Objective To establish an effective approach for rapid and comprehensive analysis on the absorbed and metabolic components in rats after ig administration of Yuanhu Zhitong Dropping Pill（YHZT）. Methods Based on the combination of UPLC-Q-TOF/MS and multivariate statistical analysis, the absorbed prototype constituents and their metabolites in rat plasma were rapidly analyzed and identified, and the components absorbed into brain were further identified by comparing the extracted ion chromatograms（EICs） of control and brain tissue samples of dosed rats. Results A total of 38 YHZT-related xenobiotic compounds were detected and identified as the potential bioactive constituents in rat plasma, including 24 absorbed prototype constituents and 14 metabolites. In particular, of all prototype constituents, 14 were also detected in rat brain tissue, indicating that they could penetrate the blood-brain barrier and enter into brain. Conclusion An effective method is established and applied to analyze the potential bioactive constituents in YHZT, which provides a pathway to further investigate the pharmacological pattern and mechanism of YHZT.

Shexiang Tongxin dropping pill(麝香通心滴丸)protects against sodium laurate-induced coronary microcirculatory dysfunction in rats

OBJECTIVE:To investigate the protective effects of Shexiang Tongxin dropping pill(麝香通心滴丸,STDP)in a rat model of coronary microcirculatory dysfunction(CMD).METHODS:Sprague-Dawley rats were allocated randomly into four groups:sham,CMD model,STDP,and nicorandil.After 4 weeks of treatment,CMD was induced by injection of sodium laurate(0.2 m L,2 g/L)into the left ventricle while obstructing the ascending aorta.Rats in the sham group underwent an identical surgical procedure but were administered physiological(0.9%)saline(0.2 m L).Twenty-four hours after surgery,blood samples were collected for biochemical analyses and enzyme-linked immunosorbent assays.Heart tissues were removed for histopathology staining;apoptosis and inflammatory cytokines were examined by Western blotting.RESULTS:The STDP group had a lower level of creatine kinase-myocardial band,lactate dehydrogenase,and cardiac troponin-I than that in the CMD model group.Infiltration of inflammatory cells,myocardial ischaemia,and microthrombosis were relieved in the STDP group compared with CMD model group.Levels of endothelin-1,nuclear factor-kappa B,tumour necrosis factor-α,interleukin-6,interleukin-1β,malondialdehyde,B-cell lymphoma(Bcl)-2-associated X protein,and caspase-3 were lower,and levels of nitric oxide,Bcl-2,and superoxide dismutase were higher,in the STDP group in comparison with the CMD model group.CONCLUSION:STDP pretreatment improved the CMD induced by sodium laurate via anti-inflammatory,anti-apoptosis,and anti-oxidant mechanisms.

Shexiang Tongxin Dropping Pill(麝香通心滴丸)Reduces Coronary Microembolization in Rats via Regulation of Mitochondrial Permeability Transition Pore Opening and AKT-GSK3βPhosphorylation

Objective To investigate the protective effects of Shexiang Tongxin Dropping Pill(麝香通心滴丸,STDP)following sodium laurate-induced coronary microembolization(CME)in rats.Methods Forty rats were divided into 4 groups:the control(sham)group,CME group,low-dose STDP pretreatment group(20 mg·kg^(−1)·d^(−1)),and high-dose STDP pretreatment group(40 mg·kg^(−1)·d^(−1)).The rats were intragastric administrated with STDP 2 weeks before operation.Moreover,the histopathological alterations were observed using optical microscopy and transmission electron microscopy.Antioxidant biomarkers were analyzed by enzyme-linked immunosorbent assay.Mitochondrial functions including the mitochondrial permeability transition pore(mPTP)mtDNA copy number were determined and proteins of AKT/GSK3βwere analyzed by Western blot.Results The rats in the CME group showed a significant increase in the fibrinogen-like protein 2 expression level and mitochondrial dysfunction and a decrease in the expression level of antioxidant biomarkers(superoxide dismutase and catalase,P<0.01 for all).In contrast,the rats in the low-and high-dose STDP pretreatment groups showed a significant decrease in coronary microthrombi(P<0.05);moreover,STDP restored the antioxidant-related protein activities and mitochondrial function,inhibited mPTP opening,decreased AKT-Ser473 phosphorylation,and increased GSK3β-Ser9 phosphorylation(P<0.05 or P<0.01).Conclusion STDP may be useful for treatment of CME,possibly via regulation of mPTP opening and AKT/GSK3βphosphorylation.

Therapeutic effects of Qishen Yiqi Dropping Pill on myocardial injury induced by chronic hypoxia in rats

The present study was designed to determine the effects of a traditional Chinese medicine, called Qishen Yiqi Dropping Pill on chronic hypoxia-induced myocardial injury. To establish a rat chronic hypoxia model to be used in the evaluation of the therapeutic effects of the Qishen Yiqi Dropping Pill, Sprague-Dawley （SD） rats were randomly divided into three groups： the control, model, and treatment groups （n - 10 per group）. The animals were housed in a plexiglass container. The control animals were under normal oxygen concentration and the model and treatment groups were exposed to air and nitrogen for 5 weeks. The rats in the treatment group were orally administered the Qishen Yiqi Dropping pill （35 mg-kg-1.d-1） for 5 weeks. After the treatment, the cardiac function and morphology were analyzed, and the expression levels of hypoxia-inducible factor la （HIF-1a） were determined using Western blotting. Our results indicated that the cardiac function was impaired, cell apoptosis was enhanced, and HIF-1a expression was up-regulated in the model group, compared to the control group. These changes were ameliorated by the treatment with the Qishen Yiqi Dropping Pill. In conclusion, Qishen Yiqi Dropping pill can ameliorate myocardial injury induced by chronic hypoxia, improve cardiac function, and decrease myocardial cell apoptosis, which may provide a basis for its clinical use for the treatment of chronic cardiovascular diseases

Antiplatelet and myocardial protective effect of Shexiang Tongxin Dropping Pill in patients undergoing percutaneous coronary intervention:A randomized controlled trial

Background:High on-clopidogrel platelet reactivity could be partially explained by loss-of-function alleles of CYP2 C19,the enzyme that converts clopidogrel into its active form.Shexiang Tongxin Dropping Pill(STDP)is a traditional Chinese medicine to treat angina pectoris.STDP has been shown to improve blood flow in patients with slow coronary flow and attenuate atherosclerosis in apolipoprotein E-deficient mice.However,whether STDP can affect platelet function remains unknown.Objective:The purpose of this study is to examine the potential effects of STDP on platelet function in patients undergoing percutaneous coronary intervention(PCI)for unstable angina.The interaction between the effects of STDP with polymorphisms of CYP2 C19 was also investigated.Design,participants and intervention:This was a single-center,randomized controlled trial in patients undergoing elective PCI for unstable angina.Eligible subjects were randomized to receive STDP(210 mg per day)plus dual antiplatelet therapy(DAPT)with clopidogrel and aspirin or DAPT alone.Main outcome measures:The primary outcome was platelet function,reflected by adenosine diphosphate(ADP)-induced platelet aggregation and platelet microparticles(PMPs).The secondary outcomes were major adverse cardiovascular events(MACEs)including recurrent ischemia or myocardial infarction,repeat PCI and cardiac death;blood biomarkers for myocardial injury including creatine kinase-MB isoenzyme(CK-MB)and high-sensitive troponin I(hs Tn I);and biomarkers for inflammation including intercellular cell adhesion molecule-1(ICAM-1),vascular cell adhesion molecule-1(VCAM-1),monocyte chemoattractant protein-1(MCP-1)and galectin-3.Results:A total of 118 subjects(mean age:[66.8±8.9]years;male:59.8%)were included into analysis:58 in the control group and 60 in the STDP group.CYP2 C19 genotype distribution was comparable between the 2 groups.In comparison to the control group,the STDP group had significantly lower CKMB(P<0.05)but similar hs Tn I(P>0.05)at 24 h after PCI,lower ICAM-1,VCAM-1,MCP-1 and galectin-3 at 3 months(all P<0.05)but not at 7 days after PCI(P>0.05).At 3 months,the STDP group had lower PMP number([42.9±37.3]vs.[67.8±53.1]counts/μL in the control group,P=0.05).Subgroup analysis showed that STDP increased percentage inhibition of ADP-induced platelet aggregation only in slow metabolizers(66.0%±20.8%in STDP group vs.36.0%±28.1%in the control group,P<0.05),but not in intermediate or fast metabolizers.The rate of MACEs during the 3-month follow-up did not differ between the two groups.Conclusion:STDP produced antiplatelet,anti-inflammatory and cardioprotective effects.Subgroup analysis indicated that STDP inhibited residual platelet reactivity in slow metabolizers only.

Effect of Composite Salviae Dropping Pill on Endothelin Gene Expression in Circulating Endothelial Cells of Patients with Coronary Heart Disease

Objective: To explore the effect of composite Salviae droping pill(CSDP) on endothelin (ET-1) gene expression in circulating endothelial cells. Mothods: Seventy cases of stable angina pectoris were randomly divided into two groups, the CSDP group and the isosorbide dinitrate (ID) group. They were treated with CSDP and ID respectively,their ET-1 gene expression in endothelial cells of peripheral circulation was measured before and after treatment by reverse transcriptase-polymerase chain reaction(RT-PCR) and compared between the two groups as well as with that of healthy subjects. Results: Electrophoresis banding of 546 bp cDNA procured from 59 cases of 70 patients was positive, while no positive banding was obtained from the healthy subjects. Six cases from the 29 patients treated with CSDP had their banding turned to negative,while in the ID group,no one turned to negative after treatment. And ET-1 PCR product (absorbed optic density) in the CSDP group was markedly lower than that in the ID group, P＜0.05. Conclusion: DSP could directly inhibit ET-1 gene expression in endothelial cells of peripheral circulation.