Dengzhan Shengmai Capsule Research Articles

Dengzhan Shengmai capsule ameliorates cognitive impairment via inhibiting ER stress in APP/PS1 mice

Ethnopharmacological relevanceAlzheimer's disease (AD) is a common type of neurodegenerative disease with the β-amyloid plaques (Aβ) deposition. Previously, Dengzhan Shengmai capsule (DZSM) has been shown to reduce the pathology associated with AD, but the underlying mechanism is unclear. Aim of studyThis study investigated the potential mechanisms of DZSM against AD. Materials and methodsThe six-month-old wild-type male mice and APP/PS1 double transgenic male mice were administered 0.9 % saline or DZSM for 8 weeks by gavage. Open field test, new object recognition test, and Morris Water maze test were used to assess spatial learning and memory. Aβ plaques in brains were visualized using ThT staining. Nissl staining, TUNEL staining, and Western blot analyses were used to detect the neuronal function and apoptosis level. The superoxide dismutase (SOD), glutathione peroxidase assay kit (GSH-Px), and malondialdehyde (MDA) kits were performed to assess oxidative stress levels. Then, immunofluorescence and Western blot analysis were applied to evaluate ER stress pathway protein levels. Finally, HT22 cells were treated by Aβ1-42 with or without DZSM medicated serum. Cell viability was assessed using the CCK-8 assay, and Western blot analysis was applied to evaluate ER stress pathway protein levels. ResultsOpen filed test, new object recognition test and Morris Water maze test showed that DZSM restored cognitive disorders in APP/PS1 mice. Immunohistochemistry and Thioflavin T staining results indicated that DZSM reduced Aβ plaques in the brain. Deeper and denser Nissl bodies were found in APP/PS1 mice after DZSM administration. Besides, APP/PS1 mice treated with DZSM showed a lower level of TUNEL and Bax/Bcl-2 ratio. DZSM improved the acetylcholine (ACh), choline acetyltransferase (ChAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) activity while reducing acetylcholinesterase (AChE) and malondialdehyde (MDA) activity. In addition, the levels of ER stress pathway containing Phospho-PKR-like ER kinase (P-PERK), phosphorylate eukaryotic initiation factor 2 (P-eIF2α), activating transcription factor 4 (ATF4), glutamine-rich protein 1 (QRICH1), phosphorylate inositol-requiring protein 1α (P-IRE1α), the spliced form of X-box binding protein 1 (XBP1s), activating transcription factor-6 (ATF6) and C/EBP homologous binding protein (CHOP) were decreased by DZSM. CCK-8 results indicated that DZSM medicated serum played cytoprotective effects on Aβ1-42-induced HT22 cells. Western blot results suggested DZSM possibly inhibited ER stress pathways in Aβ1-42-induced HT22 cells. ConclusionThe potential protective mechanism of DZSM on cognitive impairment in AD might be related to ER stress pathways.

A stroke organoids-multiomics platform to study injury mechanism and drug response

Stroke is one of the top causes of death and disability worldwide, and its pathogenesis and mechanism have not been fully elucidated. Several agents have shown protective effects against stroke in animal models; however, few studies have shown obvious effects in clinical practice. This might be due to differences in brain structure and physiological function between humans and rodents. In this study, we established a hypoxic stroke model in human-induced pluripotent stem cell (hiPSC)-derived brain organoids to simulate the hypoxic stroke caused by ischemia. Then, by combining proteomics, single-cell transcriptome analysis, and histopathological analysis, a significant increase of three types of astrocytes was identified and they showed different responses to hypoxic environments; also the main type of astrocyte that cause brain tissue hyperplasia in ischemia brains was identified. In addition, the cortical excitatory neurons had signs of apoptosis and aging after hypoxia both in vivo and in vitro. Most importantly, we identified a possible role of a traditional Chinese medicine formula called DengZhanShengMai capsule in ischemic and hypoxic stroke treatment through regulation of lipid metabolism related biological functions. These results indicate that the combination of brain organoids and multiomics method is helpful for developing a new strategy to direct study stroke, and could provide a promising platform for drug screening of stroke in the future.

Investigation of the efficacy of Dengzhan Shengmai capsule against heart failure with preserved ejection fraction

Ethnopharmacological relevanceHeart failure with preserved ejection fraction (HFpEF) has emerged as a condition with high incidence and mortality rates in recent years. Dengzhan Shengmai capsule (DZSMC) is a Chinese patent medicine based on the classic recipe “Shengmai powder”. The relevant Chinese medicine ratio of Erigeron breviscapus (Vaniot) Hand.-Mazz., Panax ginseng C.A.Mey., Schisandra chinensis (Turcz.) Baill., and Ophiopogon japonicus (Thunb.) Ker Gawl. Is 30 : 6: 6 : 11. Traditional Chinese medicine (TCM) is being increasingly explored as a safe and effective treatment modality for HFpEF. Clinical studies have shown that DZSMCs can effectively treat heart failure, however, the mechanism of action of DZSMCs in the treatment of HFpEF are still not clear.Aim of the study: To investigate the efficacy and underlying mechanisms of Dengzhan Shengmai capsule (DZSMC), in the treatment of HFpEF by focusing on its ability to treat microvascular inflammation. Materials and methodsFirst, the efficacy of DZSMCs against HFpEF was predicted by network pharmacology. After 3 days of adaptive feeding in SPF-grade polypropylene cages, the mice in the Model group, DZSMC group, and Captopli group underwent single kidney resection, and micropumps were implanted in their backs for continuous infusion of aldosterone at a rate of 0.3 μg/h for 4 weeks. Moreover, the mice were given DZSMCs or Captopli via oral gavage for four weeks. Overall, cardiac function was evaluated in mice, and cardiac ultrasound and blood biochemical indices were evaluated in HFpEF mice. ResultsDZSMCs can ameliorate myocardial hypertrophy and cardiomyocyte damage caused by excessive myocardial stress, ultimately mitigating long-term cardiac impairment; it aids in the restoration of myocardial fibre proliferation and enhances mitochondrial morphology and function.In a murine model of ventricular hypertrophy and left ventricular dysfunction, which are indicative of cardiac insufficiency, the administration of DZSMCs resulted in notable improvements. Echocardiographic and overall assessments of cardiac function revealed a reduction in cardiac dysfunction and ventricular hypertrophy post-DZSMC intervention.Moreover, intervention with DZSMCs led to a reduction in the serum levels of several markers associated with chronic systemic inflammation, such as sST2, IL1RL1, CRP, and IL-6. Simultaneously, the levels of indicators of microvascular inflammation, including VCAM and E-SELECTIN, also decreased following DZSMC intervention.These findings suggest the potential multifaceted impact of DZSMCs in alleviating cardiac abnormalities, mitigating systemic inflammation, and reducing microvascular inflammatory markers, highlighting their promising therapeutic role in managing myocardial health. ConclusionsThese results provide novel evidence that DZSMCs improve HFpEF by regulating microvascular inflammation.

Dengzhanshengmai capsule alleviates heart failure and concomitantly decreases phenylacetylglutamine level, interacting with the intestinal microflora in rats.

Heart failure (HF) is an advanced stage of most heart diseases. Some studies reported that Dengzhanshengmai (DZSM) capsule may improve HF, but its mechanisms are unclear. This study attempts to determine the function of DZSM in treating HF and investigates its potential mechanism. We demonstrated that DZSM can considerably reduce systemic inflammation, improve intestinal barrier functions and enhance cardiac functions in HF rats. Further investigations displayed that the beneficial effects of DZSM were related to the reduction of gut microbiota metabolite phenylacetylglutamine (PAGln) levels in serum and heart tissue. In addition, we demonstrated that PAGln can exacerbate the severity of HF in rats, and the serum PAGln levels in HF patients were higher than in healthy subjects. Moreover, by using microbial sequencing, we found that DZSM could alter the composition and function of the intestinal microbiota in HF rats, including decreased relative abundance of Turicibacter and Turicibacter_sp.TS3, and regulated the gene expression of PAGln synthesis-related enzymes. Therefore, our findings have contributed novel perspectives on the involvement of DZSM in treating HF, specifically in its regulation of intestinal flora and associated detrimental metabolites. Furthermore, our results have offered empirical evidence supporting the utilization of DZSM as a therapeutic approach for HF.

Altered synaptic currents, mitophagy, mitochondrial dynamics in Alzheimer's disease models and therapeutic potential of Dengzhan Shengmai capsules intervention

Emerging research suggests a potential association of progression of Alzheimer's disease (AD) with alterations in synaptic currents and mitochondrial dynamics. However, the specific associations between these pathological changes remain unclear. In this study, we utilized Aβ42-induced AD rats and primary neural cells as in vivo and in vitro models. The investigations included behavioural tests, brain magnetic resonance imaging (MRI), liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis, Nissl staining, thioflavin-S staining, enzyme-linked immunosorbent assay, Golgi-Cox staining, transmission electron microscopy (TEM), immunofluorescence staining, proteomics, adenosine triphosphate (ATP) detection, mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) assessment, mitochondrial morphology analysis, electrophysiological studies, Western blotting, and molecular docking. The results revealed changes in synaptic currents, mitophagy, and mitochondrial dynamics in the AD models. Remarkably, intervention with Dengzhan Shengmai (DZSM) capsules emerged as a pivotal element in this investigation. Aβ42-induced synaptic dysfunction was significantly mitigated by DZSM intervention, which notably amplified the frequency and amplitude of synaptic transmission. The cognitive impairment observed in AD rats was ameliorated and accompanied by robust protection against structural damage in key brain regions, including the hippocampal CA3, primary cingular cortex, prelimbic system, and dysgranular insular cortex. DZSM intervention led to increased IDE levels, augmented long-term potential (LTP) amplitude, and enhanced dendritic spine density and length. Moreover, DZSM intervention led to favourable changes in mitochondrial parameters, including ROS expression, MMP and ATP contents, and mitochondrial morphology. In conclusion, our findings delved into the realm of altered synaptic currents, mitophagy, and mitochondrial dynamics in AD, concurrently highlighting the therapeutic potential of DZSM intervention.

Single-cell RNA sequencing reveals that VIM and IFITM3 are vital targets of Gengzhan Shengmai capsule to protect against cerebral ischemic injury.

Ischemic stroke is one of the leading causes of mortality, but therapies are limited. Dengzhan Shengmai (DZSM) capsule was included by the Chinese Pharmacopoeia 2015 and has been broadly used for the treatment of ischemic stroke. However, the mechanism of DZSM against ischemic stroke is unclear. This study used RNA sequencing (RNA-seq) and single-cell RNA sequencing (scRNA-seq) to investigate the mechanism of action of DZSM against ischemic stroke. The rats were randomly divided into six groups: the Sham, I/R (water), I/R+DZSM-L (0.1134 g/kg), I/R+DZSM-H (0.4536 g/kg), I/R+NMDP (20 mg/kg), and I/R+Ginaton (20 mg/kg). The rats were administrated drugs for 5 days then followed by the ischemic brain injury caused by middle cerebral artery occlusion (MCAO). The neuroprotective effect was assessed by infraction rate, neurological deficit scores, regional cerebral blood flow (rCBF), hematoxylin and eosin (H&E) staining, and Nissl staining. Based on RNA-seq and scRNA-seq, the vital biological processes and core targets of DZSM against cerebral ischemia were revealed. Enzyme-linked immunosorbent assay (ELISA) and immunofluorescence (IF) staining were used to investigate the vital biological processes and core targets of DZSM against ischemic stroke. Administration of DZSM significantly reduced the infarction rate and Zea Longa score, Garcia JH score, and ameliorated the reduction in rCBF. And alleviated the neuronal damage, such as increased neuronal density level and Nissl bodies density level. RNA-seq analysis revealed that DZSM played important roles in inflammation and apoptosis. ELISA and IF straining validation confirmed that DZSM significantly decreased the expression of IL-6, IL-1β, TNF-α, ICAM-1, IBA-1, MMP9, and Cleaved caspase-3 in MCAO rats. ScRNA-seq analysis identified 8 core targets in neurons including HSPB1, SPP1, MT2A, GFAP, IFITM3, VIM, CRIP1, and GPD1, and VIM and IFITM3 was verified to be decreased by DZSM in neurons. Our study illustrates the neuroprotective effect of DZSM against ischemia stroke, and VIM and IFITM3 were identified as vital targets in neurons of DZSM in protecting against MCAO-induced I/R injury.

Network Meta-analysis of Qi-benefiting and blood-activating Chinese patent medicines against ischemic stroke

This study aimed to compare the efficacy of Qi-benefiting and blood-activating Chinese patent medicines in the treatment of ischemic stroke with network Meta-analysis. CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, and Cochrane Library were searched from database inception to October 2022 for randomized controlled trial(RCT) on 11 Qi-benefiting and blood-activating Chinese patent medicines in the treatment of ischemic stroke. The risk of bias plot was made by RevMan 5.3, and network Meta-analysis and efficacy ranking were performed by Stata 17. Ninety-two RCTs were included, involving 10 608 patients. According to the network Meta-analysis, in terms of the clinical total effective rate, surface under the cumulative ranking curve(SUCRA) as followed: Qilong Capsules+conventional western medicine>Zhishe Tongluo Capsules+conventional western medicine>Longshengzhi Capsules+conventional western medicine>Naoxintong Capsules+conventional western medicine>Tongsaimai Tablets+conventional western medicine>Naoan Capsules+conventional western medicine>Naoluotong Capsules+conventional western medicine>Xiaoshuan Changrong Capsules+conventional western medicine>Dengzhan Shengmai Capsules+conventional western medicine=Tongxinluo Capsules+conventional western medicine>Naomaitai Capsules+conventional western medicine. In terms of the improvement in National Institute of Health stroke scale(NIHSS) score, SUCRA as followed: Longshengzhi Capsules+conventional western medicine>Naomaitai Capsules+conventional western medicine>Naoxintong Capsules+conventional western medicine>Dengzhan Shengmai Capsules+conventional western medicine>Xiaoshuan Changrong Capsules+conventional western medicine>Naoluotong Capsules+conventional western medi-cine>Tongxinluo Capsules+conventional western medicine>Naoan Capsules+conventional western medicine>Qilong Capsules+conventional western medicine. In terms of safety, the overall adverse reactions/events of Qi-benefiting and blood-activating Chinese patent medicines + conventional western medicine were less than those of the control group. Since Qilong Capsules+conventional western medicine and Zhishe Tongluo Capsules+conventional western medicine were preferred to improve the clinical total effective rate. In the aspect of improving NIHSS score, Longshengzhi Capsules+conventional western medicine and Naomaitai Capsules+conventional western medicine were first options. Due to the lack of direct comparisons between drugs, the overall quality of RCT was not high, so more studies are needed to verify the strength of the evidence.

Dengzhan Shengmai capsule attenuates cardiac fibrosis in post-myocardial infarction rats by regulating LTBP2 and TGF-β1/Smad3 pathway

BackgroundCardiac fibrosis contributes to myocardial remodeling after myocardial infarction (MI), which may facilitate the progression to end-stage heart failure. Dengzhan Shengmai capsule (DZSMC), a traditional Chinese formula derived from Shen-mai powder, has shown remarkable therapeutic effects against cardiovascular diseases. However, the effect of DZSMC on cardiac fibrosis and its potential mechanism are ill-defined. PurposeTo evaluate the effects of DZSMC on cardiac fibrosis after myocardial infarction (MI) and investigate its underlying mechanism. MethodIn vivo, MI rat models were established by permanently ligation of left anterior descending coronary arteries (LAD) and then were intragastrically treated with DZSMC or captopril for 5 weeks. Ex vivo, an everted intestinal sac model was used to study the intestinal absorption components of DZSMC, which were further identified through an ultra-performance liquid chromatography tandem mass spectrometry (UHPLC-MS) method. In vitro, a myocardium fibrotic model was constructed by stimulating primary cardiac fibroblasts (CFs) with 1 μM Ang II. Subsequently, the absorbent solution of DZSMC from the intestinal sac was performed on the cell models to further elucidate its anti-fibrotic effects and underling mechanism. ResultsIn vivo results showed that DZSMC significantly improved cardiac function and inhibited pathological myocardial fibrosis in post-MI rats in a dose dependent manner. Histological analysis and western blot results demonstrated that DZSMC treatment significantly reduced the expression of extracellular matrix (ECM)-related proteins, including LTBP2, TGF-βR1, Smad3 and pSmad3, in myocardial tissue of MI rats. Ex vivo results showed that 18 absorbed components were identified, mainly consisting of phenolic acids, flavonoids and lignans, which may be responsible for the anti-fibrotic effects. Further in vitro results validated that DZSMC attenuated myocardial fibrosis by suppressing the expression of LTBP2, TGF-β1 and pSmad3. ConclusionDZSMC ameliorates cardiac function and alleviates cardiac fibrosis, which may be mediated by inhibition of CFs activation and reduction of excessive ECM deposition via LTBP2 and TGF-β1/Smad3 pathways.

A comprehensive perspective on the disposition, metabolism, and pharmacokinetics of representative multi-components of Dengzhan Shengmai in rats with chronic cerebral hypoperfusion after oral administration.

Dengzhan Shengmai capsule (DZSM), an evidence-based Chinese medicine comprising Erigeron breviscapus (Vaniot) Hand. -Mazz., Panax ginseng C.A.Mey., Ophiopogon japonicus (Thunb.) Ker Gawl., and Schisandra chinensis (Turcz.) Baill., exhibits an excellent efficacy in treating cardio- and cerebrovascular diseases. It contains caffeoyl compounds, flavonoids, saponins, and lignans as primary active components. However, so far, the characteristics of disposition, metabolism, and pharmacokinetics of its active components remain mostly unclear. To elucidate disposition, metabolism, and pharmacokinetics of representative components of DZSM in rats with chronic cerebral hypoperfusion (CCH) by integrating ex vivo and in situ approaches. Exposure and distribution of absorbed prototypes and their metabolites were comprehensively investigated using sensitive LC-MS/MS and high-resolution LC-Q-TOF/MS. Pharmacokinetics of representative 16 components (12 prototypes and 4 metabolites) with different chemical categories, relatively high in vivo levels, wide tissue distribution, and reported neuroprotective activities were profiled. The ex vivo everted gut sac and in situ linked-rat models were adopted. Representative 12 prototypes including 6 caffeoyl compounds (CA, 5-CQA, 3-CQA, 4-CQA, 1,3-CQA, and 3,4-CQA), 1 flavonoid (Scu), 2 saponins (Rd and Rg2), and 3 lignans (SchA, SchB, and SolA) presented characteristic absorption, disposition, and pharmacokinetics profiles in CCH rats. The caffeoyl compounds and flavonoid were well absorbed, exhibited wide distribution, and underwent extensive intestinal metabolism, such as methylation, isomerization, and sulfoconjugation. For CA, 5-CQA, Scu, and 4 related metabolites, the enterohepatic circulation was observed and resulted in bimodal or multimodal pharmacokinetic profiles. Saponins showed relatively low systemic exposure and limited distribution. The PPD-type ginsenoside Rd exhibited longer elimination half-life and systemic circulation than the PPT-type ginsenoside Rg2. No enterohepatic circulation was observed regarding saponins, suggesting that the multimodal pharmacokinetic profile of Rd could be due to its multi-site intestinal absorption. Lignans presented a low in vivo exposure and broad distribution. They were mainly transformed into hydroxylated metabolites. Corresponding to its bimodal pharmacokinetic profile, one metabolite of lignans completed the enterohepatic cycle. The disposition, metabolism, and pharmacokinetic profiles of representative active components of DZSM were comprehensively characterized and elucidated.

Multi-omics and network pharmacology study reveals the effects of Dengzhan Shengmai capsule against neuroinflammatory injury and thrombosis induced by ischemic stroke

Ethnopharmacological relevanceDengzhan Shengmai capsule (DZSM) is a traditional herb medicine used by Dai, an ethnic-minority community living in Xishuang banna tropical rainforest in Southwest of China. It was originally intended to treat disorders caused by insufficient brain function, characterized by gibberish, unresponsiveness, or confusion. Accumulating clinical evidences exhibited that it is effective on treating ischemic stroke (IS). However, the action of DZSM against IS needs to be further elucidated. Aim of the studyTo investigate the effect of DZSM and its active components against IS and the way of its action by multi-omics and network pharmacology. Materials and methodsA middle cerebral artery occlusion/reperfusion (MCAO/R) rat model was established to investigate the effect of DZSM on the focal cerebral ischemia/reperfusion injury. An integrated strategy combining metabolomics, network pharmacology and transcriptomics was performed to systematically clarify the underlying mechanism of action of DZSM against IS. AutoDock Vina was applied to conduct molecular docking simulation for the binding between the potential active compounds and targets. Arachidonic acid (AA) induced platelet aggregation and lipopolysaccharide (LPS) stimulated microglial cells BV2 inflammation models were applied for the in vitro validation of effects of DZSM and its potential active compounds. ResultsIn MCAO/R rats, DZSM could significantly reduce the infarct volume. Putative target prediction and functional enrichment analysis based on network pharmacological indicated that the key targets and the potential active compounds played important roles in DZSM's treatment to IS. The targets included four common genes (PTGS1, PTGS2, NFKB1 and NR1I2) and five key TFs (NFKB1, RELA, HIF1A, ESR1 and HDAC1), whilst 22 potential active compounds were identified. Molecular docking indicated that good binding affinity have been seen between those compounds and NR1I2, NFKB1, and RELA. Multi-omics study revealed that DZSM could regulate glutamate by influencing citrate cycle and glutamate involved pathways, and have showed neuroprotection activity and anti-inflammation activity by inhibiting NF-κB pathway. Neuroprotective effects of DZSM was validated by regulating of NF-κB signaling pathway and its downstream NO, TNF-α and IL-6 cytokines contributed to the activity of DZSM and its active compounds of scutellarin, quercetin 3-O-glucuronide, ginsenoside Rb1, schizandrol A and 3, 5-diCQA, whilst the antithrombotic activity of DZSM and its active compounds of schisanhenol, apigenin and schisantherin B were screened out by anti-platelet aggregation experiment. ConclusionDZSM could against IS via regulating its downstream NO, TNF-α and IL-6 cytokines through NF-κB signaling pathway and alleviating thrombosis.

Dengzhan Shengmai capsule versus Aspirin in the treatment of carotid atherosclerotic plaque: A single-centre, non-inferiority, prospective, randomised controlled trial

BackgroundAspirin is an effective antiplatelet agent for the treatment of carotid atherosclerosis. However, the high risk of bleeding events associated with the drug makes it necessary to seek a safer alternative, with similar or more efficacy than aspirin. Dengzhan Shengmai (DZSM) capsules have been widely used to treat carotid atherosclerosis, and if proven to be non-inferior to aspirin, it may be preferable over the latter for carotid atherosclerosis treatment due to its numerous advantages. We conducted a randomised trial to test the non-inferiority of DZSM to aspirin for the treatment of carotid atherosclerotic plaques. MethodsWe performed a single-centre, prospective, open-label, randomised non-inferiority trial. Patients with carotid atherosclerotic plaques were enrolled and randomly assigned (1:1) to receive either DZSM capsules or aspirin. The follow-up period was 12 months. The primary outcome was the mean change in carotid intima-media thickness (IMT). Secondary outcomes included ischaemic events, rate of lumen stenosis, lipid levels, and plaque scores, length, counts, and vulnerability. Adverse events and laboratory test results were recorded as safety outcomes. The non-inferiority of DZSM was demonstrated when the lower limit of the one-sided 97.5% confidence interval (CI) of the difference in IMT between groups was more than -0.06 mm (margin of non-inferiority). This trial has been registered at ClinicalTrials.gov (CHiCTR1900021365). ResultsFrom 1 April 2019 to 30 September 2019, 150 patients were enrolled, and there was no statistical difference in demographics between the groups. Intention-to-treat analysis showed that the decrease in IMT(∆IMT) was 0.216 ± 0.160 and 0.225 ± 0.149 mm in the DZSM and aspirin groups, respectively. The one-sided 97.5% CI for the difference between ∆IMTs was (-0.0593, +∞). The non-inferiority of DZSM was demonstrated (Pnon-inferiority = 0.0234). There was no significant difference in the incidence of ischaemic events between the groups (P = 1.0). The DZSM group had significantly reduced plaque scores (P < 0.0001), length (P < 0.0001), and counts (P < 0.0001), and improved plaque vulnerability (P < 0.0001). The DZSM group also had reduced levels of low-density lipoprotein cholesterol (LDL-C) (P < 0.0001). Finally, the DZSM group had a lower incidence of total adverse events (14.7% vs. 28%, P = 0.046), especially gastrointestinal discomfort (5.3% vs. 16%, P = 0.034). Although there was no significant difference in bleeding events (0 vs. 5.3%, P = 0.120), the DZSM group tended to have a lower incidence. ConclusionThis trial demonstrated that DZSM was not inferior, in efficacy, to aspirin in treating carotid atherosclerotic plaques, and was found to be superior to aspirin in terms of safety. This study provides a new approach for treating carotid plaques, especially in aspirin-intolerant patients.

Time-related accurate investigation of multicomponent drug interventions in heart failure

BackgroundChronic heart failure (CHF) is one of the most common disabling, painful, and deadly syndromes. As a syndrome, heart failure (HF) has been divided into more specific processes, and these processes may occur at the same time or have a precedence. In addition, drug intervention in the process of HF has the most appropriate time point, which means that it is not always the best time to intervene with this drug during the entire course of HF. Traditional Chinese medicine (TCM) Dengzhan Shengmai capsule (DZSMC), a TCM formula, is known as a multitarget complementary medicine that is widely used clinically to treat HF in Asian countries. However, because the mechanism by which DZSMCs treat HF has not been demonstrated comprehensively, the uncertainty of the occasion of drug use makes the precise intervention of DZSMCs a challenge. MethodsIn this article, for precise research on the time point of DZSMC intervention during the process of HF, we applied the time-related proteomics data we measured combined with proteomics data reported and online database to perform a precise prediction to learn DZSMC intervention in specific progression and time points of HF. Then the precise prediction was validation in rats after ligation of left anterior descending coronary artery. ResultsWe demonstrate that DZSMC can improve the cardiac function of myocardial infarction (MI) rats by raising the cardiac ejection fraction (EF) and slowing down the thinning of the anterior wall of the left ventricle. In addition, we found that the appropriate time point for DZSMC intervention is when the serum level of voltage-dependent calcium channel subunit alpha-2/delta-2 (Cacna2d2) increases and that DZSMCs play their role in delaying HF mainly by reducing the myocardial load through decreasing Cacna2d2. ConclusionIn this study, we used a multidimensional data integration strategy by combining the proteomics data and bioinformatic tools to explore the suitable time points for DZSMC intervention in HF induced by MI on a rat model. We verified the efficiency of DZSMC in treating HF and found that DZSMC can improve HF by increasing the cardiac EF, FS and retarding the thinning of the anterior wall of the left ventricle by echocardiography. Futhermore, the upregulated Cacna2d2 in 3 weeks post MI could be a potential signal for DZSMC intervention and DZSMC can downregulate the abnormal decrease of Cacna2d2 in 4weeks post MI. This study provides a practical and feasible method for determining a suitable time point for TCM intervention, and this is the first report of DZSMCs decreasing the serum level of Cacna2d2 to improve cardiac function.

Comparison of Traditional Chinese Medicine in the Long-Term Secondary Prevention for Patients with Ischemic Stroke: A Systematical Analysis.

Background: Keeping in view the high recurrence rate and risk of ischemic stroke, combinatorial therapy involving traditional Chinese medicine (TCM) with conventional Western medicine (WM) is receiving wider scientific attention. Thus, a systematical analysis was made to explore the efficacy of TCM+WM in the long-term secondary prevention for patients with ischemic stroke. Methods: Qualified inclusion and exclusion criteria were set up beforehand, and two researchers independently read the articles, extracted data, and evaluated the quality of included articles according to Cochrane Reviewer’s Handbook 5.1 method. For the sake of comprehensive data acquisition, seven databases from the time of their establishment to May 5, 2021, have been searched completely. Additionally, pairwise meta-analysis was made to compare TCM+WM vs. WM, and network meta-analysis was conducted by frequentist random effects models for the comparison of different kinds of TCM+WM via indirect evidence. The primary outcomes defined were recurrent stroke and NIHSS. Secondary outcomes were fibrinogen (Fib) fasting blood glucose (FBG), triglycerides (TG), and total cholesterol (TC). Safety outcomes were outlined as all-cause mortality and adverse events (AEs). Furthermore, Stata16.0 software was used to accomplish the systematical analysis and cluster analysis. Results: In total, 47 qualified randomized controlled trials (RCTs) including 10,732 patients were taken into consideration. Seven traditional Chinese medicines included in the study are Naoxintong capsule (NXT), Tongxinluo capsule (TXL), Buyang Huanwu decoction (BYHW), Naomaitai capsule (NMT), Dengzhan Shengmai capsule (DZSM), Naoshuantong capsule (NST), and Maixuekang capsule (MXK). With respect to their primary outcomes, all kinds of TCM+WM were significantly more effective than WM (e.g., NXT in recurrent stroke (OR=0.54, P<0.01), TXL in NIHSS (WM=−1.4, P<0.01)). Additionally, the outcomes of cluster analysis indicated that MXK+WM and NST+WM had relatively good preventive effects for recurrent stroke, NIHSS, and all-cause mortality. There was no significant difference in the comparisons of AEs; however, this may arise from the lack of sufficient data. Conclusion: According to our systematical analysis, MXK+WM and NST+WM had relatively good secondary prevention effects for patients with ischemic stroke regarding recurrent stroke, NIHSS, and all-cause mortality. Nevertheless, better, high-quality, large-sample randomized clinical trials (RCTs) are required to verify our conclusions in the future. Systematic Review Registration: [https://inplasy.com/inplasy-2021-5-0036/], identifier [INPLASY202150036].

Dengzhan shengmai capsule combined with donepezil hydrochloride in the treatment of Alzheimer's disease: preliminary findings, randomized and controlled clinical trial.

To observe the effects of Dengzhan Shengmai capsule combined with donepezil hydrochloride on cognitive function, daily living ability, and safety in patients with Alzheimer's disease. A total of 294 patients with Alzheimer's disease were randomly divided into a treatment group and a control group, 147 cases each group. The control group was given oral donepezil hydrochloride 5 mg once a day, and the treatment group was given oral Dengzhan Shengmai capsule 0.36 g three times a day, based on the control group. At 3 and 6 months of treatment, the ADAS-cog score of the treatment group was 48.69±6.23 and 44.24±5.53; for the control group, 45.48±5.94 and 41.57±5.10. The difference between the two groups is statistically significant (p<0.05). At 3 and 6 months of treatment, the NO level in the treatment group was (46.28±6.68) umol/l, (43.55±7.92) umol/l, and the control group was (42.95±7.92) umol/l, (38.89±5.93) umol/l. The differences between both groups were statistically significant (p<0.05). At 3 and 6 months of treatment, ET levels in the treatment group were (156.08±17.39) ng/l, (144.91±17.60) ng/l, and the control group was (150.48±22.94) ng/l, (135.04±10.08) ng/l. Correlation analysis showed that ADAS-cog score was negatively correlated with NO and ET (p<0.001). Dengzhan Shengmai capsule combined with donepezil hydrochloride can improve cognitive function and the living capacity of patients with Alzheimer's disease, reduce the production of neurotoxic substances NO and ET, and provide higher safety.

Effects of Dengzhan Shengmai Capsule combined with butylphthalide soft capsule on oxidative stress indexes and serum Hcy and CRP levels in patients with vascular dementia

This experiment was aimed to investigate the effect of Dengzhan Shengmai capsule combined with butylphthalide soft capsule on oxidative stress indexes and serum homocysteine (Hcy) and C-reactive protein (CRP) levels in patients with vascular dementia (VD). From July 2017 to July 2019, 123 patients with VD in our hospital were selected as the research object, and each patient was assigned a random number according to the order of treatment. Among them, No. 1 to 41 were the control group A, No. 42 to 82 were the control group B, and No. 83 to 123 were the research group. Control group A was given butylphthalide soft capsules, control group B was Dengzhanshengmai capsules, and the research group was given Dengzhanshengmai capsules combined with butylphthalide softgels. Comparison of clinical efficacy, the incidence of adverse reactions, and improvement of symptoms [Montreal Cognitive Assessment Scale (MocA) score, Vascular Dementia TCM Syndrome Differentiation Scale (SDSVD) score], vascular endothelial function [NO, endothelin 1 (ET-1)], oxidative stress [lipid peroxide (LPO), superoxide dismutase (SOD), C Dialdehyde (MDA)], endoplasmic reticulum stress response (Hcy, CRP) related indicators before and after treatment in three groups. Results showed that the total effective rate of treatment in the study group was higher than that in the control groups A and B, the difference was statistically significant (p&lt;0.05). In symptom improvement, the MoCA score of the study group was higher than that of the control groups A and B after the treatment course, and the SDSVD score was lower than that of the control groups A and B (p&lt;0.05); In the vascular endothelial function section, after the course of treatment, the serum NO level in the study group was higher than that in the control groups A and B, and the ET-1 level was lower than that in the control groups A and B (p&lt;0.05). In oxidative stress experiment, after the course of treatment in the study group, the serum LPO and MDA levels were lower than those in the control groups A and B, and the SOD levels were higher than those in the control groups A and B (p&lt;0.05). Endoplasmic reticulum stress response results showed that after the course of treatment in the study group, the serum Hcy and CRP levels were lower than those in the control groups A and B (p&lt;0.05). In adverse reactions section, there was no significant difference in the incidence of adverse reactions among the three groups (p&gt;0.05). Dengzhan Shengmai Capsule combined with butylphthalide soft capsule is the first treatment for VD, with definite curative effect, which can effectively reduce the damage of vascular endothelial function and inhibit oxidative stress response, antagonize the endoplasmic reticulum stress response, thereby further alleviating dementia symptoms and improving cognitive function.

Network topology and machine learning analyses reveal microstructural white matter changes underlying Chinese medicine Dengzhan Shengmai treatment on patients with vascular cognitive impairment

With the increasing incidence of cerebrovascular diseases and dementia, considerable efforts have been made to develop effective treatments on vascular cognitive impairment (VCI), among which accumulating practice-based evidence has shown great potential of the traditional Chinese medicine (TCM). Current randomized double-blind controlled trial has been designed to evaluate the 6-month treatment effects of Dengzhan Shengmai (DZSM) capsules, one TCM herbal preparations on VCI, and to explore the underlying neural mechanisms with graph theory-based analysis and machine learning method based on diffusion tensor imaging (DTI) data. A total of 82 VCI patients were recruited and randomly assigned to drug (45 with DZSM) and placebo (37 with placebo) groups, and neuropsychological and neuroimaging data were acquired at baseline and after 6-month treatment. After treatment, compared to the placebo group, the drug groups showed significantly improved performance in Alzheimer’s Disease Assessment Scale-Cognitive subscale (ADAS-cog) score (p < 0.001) and the other cognitive domains. And with the reconstruction of white matter structural network, there were more streamlines connecting the left thalamus and right hippocampus in the drug groups (p < 0.001 uncorrected), with decreasing nodal efficiency of the right olfactory associated with slower decline in the general cognition (r = −0.364, p = 0.048). Moreover, support vector machine classification analyses revealed significant white matter network alterations after treatment in the drug groups (accuracy of baseline vs. 6-month later, 68.18 %). Taking together, the present study showed significant efficacy of DZSM treatment on VCI, which might result from white matter microstructure alterations and the topological changes in brain structural network.

Dengzhan Shengmai capsule in treatment of lower extremity arteriosclerosis obliterans

Objective To observe the clinical effect of Dengzhan Shengmai capsule in the treatment of lower extremity arteriosclerosis obliterans. Methods 60 patients were randomly divided into a control group and a treatment group, 30 for each group. The control group was treated with conventional western medicine alprostadil, while the treatment group was treated with oral Dengzhan Shengmai capsule on the basis of alprostadil, 2 capsules each time, three times a day. The two groups were treated for 14 days as a cycle and 4 cycles as a treatment course. The treatment effects were compared between these two groups. Results The total effective rate of the treatment group was 96.7%, and that of the control group 80.0% (P<0.05). After the treatment, the ABI and TBI increased significantly in both groups (all P<0.05), and the changes of ABI and TBI in the treatment group were more significant than those in the control group (both P<0.05). After the treatment, the internal diameters of the posterior femoral artery, the posterior tibial artery and the dorsal pedal artery of the two groups increased significantly (all P<0.05). In addition, the hemorheology and endothelium of the two groups were significantly improved after treatment, and were better in the treatment group (all P<0.05). Conclusions Dengzhan Shengmai capsule is effective in treating lower extremity arteriosclerosis obliterans, through improving microcirculation, inhibiting thrombosis, and regulating the release of vascular endothelial factors. Key words: Dengzhan Shengmai capsule; Lower extremity arteriosclerosis obliterans; Efficacy

Dengzhan Shengmai capsules and their active component scutellarin prevent cognitive decline in APP/PS1 mice by accelerating Aβ aggregation and reducing oligomers formation

There is currently no effective treatment to prevent the progress of Alzheimer’s disease (AD). The traditional Chinese herbs Dengzhan Shengmai (DZSM) capsules and their active component scutellarin possess multiple effects and are clinically used for the treatment of cerebrovascular diseases. Scutellarin has been reported to affect Aβ aggregation. However, the effects of DZSM capsules on AD remain unknown. Through in vivo experiments, our study proved that the alleviating effects of DZSM capsules on cognitive deficits of AD mice were due to the role of scutellarin, which up-regulated low toxic amyloid plaques and down-regulated highly toxic soluble Aβ42 and Aβ40 levels in cortex. In vitro, we confirmed scutellarin’s role in accelerating transforming Aβ42 monomers into high-molecular-mass aggregates by biochemical assays, which supported the results observed in drug-treated APP/PS1 mice. In detail, the 1:10 ratio of scutellarin/Aβ42 mixtures promoted production of large β-sheet-rich fibrils whereas the 1:1 ratio promoted production of protofibrils. In addition, the binding between scutellarin and Aβ monomers was quantified by microscale thermophoresis test and the apparent dissociation constant (Kd) was 1284.4 ± 238.8 μM. What’s more, binding regions between scutellarin and Aβ fibrils were predicted by computational docking models and scutellarin might bind parallel to the long axis of Aβ42 fibrils targeting hydrophobic grooves at residues 35–36 or 39. In conclusion, DZSM capsules protected against cognitive defects of AD through scutellarin-mediated acceleration of Aβ aggregation into fibrils or protofibrils and reduction of soluble Aβ oligomers, thus suggesting potential clinical applications of DZSM capsules and scutellarin in the treatment of AD.

Research advance in chemical compounds,pharmacological action and clinical application of Dengzhan Shengmai Capsules

Dengzhan Shengmai Capsules( DZSMC),a well-known traditional Chinese medicine( TCM) formula,is comprised of the main drug of Erigeron breviscapus,and supplemented with Panax ginseng,Ophiopogon japonicus and Schisandra chinensis,with functions of supplementing Qi and nourishing Yin,promoting blood circulation and strengthening brain. DZSMC is the only Chinese patent drug with A-level evidence-based medicine in secondary prevention for stroke and ranks first among TCMs for neurological treatment. Modern studies indicate that the chemical constituents of DZSMC mainly include flavonoids,phenolic acids,lignans,saponins and so on. Pharmacological experimental studies have shown that DZSMC has such pharmacological effects as anti-oxidation,anti-inflammatory and anti-myocardial ischemia. DZSMC is mainly used in the convalescent care of ischemic cardiovascular and cerebrovascular diseases,and is often used in combination with various conventional therapeutic drugs to exert clinical efficacy through brain protection,neuroprotection,etc.,and improve clinical symptoms in patients. In this review,according to domestic and international related literature combined with research results obtained by our project,the research advances in the chemical constituents,pharmacological effects and clinical application of DZSMC have been systematically reviewed and summarized,providing reference and support for further study and secondary development of the formula.

Interactions between clopidogrel and traditional Chinese medicine.

The use of traditional Chinese medicine (TCM) has obtained more and more acceptance all over the world due to its multi-target and multi-level function characteristics. Clopidogrel is a major therapeutic option to reduce atherothrombotic events in patients with acute coronary syndrome, recent myocardial infarction, recent stroke or established peripheral arterial disease. These patients probably take TCM. Are there any interactions between clopidogrel and TCM? Whether TCM will affect the efficacy of clopidogrel or increase the adverse reactions of bleeding? Clarifying this information will help physicians make better use of TCM. A literature search was carried out using Web of Science, PubMed and the Cochrane Library to analyze the pharmacokinetic or pharmacodynamic interactions of clopidogrel and TCM. Some herbs can increase the AUC or Cmax of clopidogrel, such as Scutellarin, Danggui, Gegen, Sauchinone and Dengzhan Shengmai capsules. Whereas others can decrease clopidogrel, for example, Ginkgo and Danshen. Furthermore, some herbs can increase the AUC or Cmax of clopidogrel active metabolite, including Ginkgo and Xuesaitong tablet. And others can decrease the clopidogrel active metabolite, such as Scutellarin, Danshen, Fufang Danshen Dripping Pill and Dengzhan Shengmai capsules. Additionally, Schisandra chinensis, Danggui, Gegen and Fufang Danshen Dripping Pill can decrease the AUC or Cmax of the clopidogrel inactive metabolite, while Curcumin on the contrary. The pharmacodynamics of Panax notoginseng, Notoginsenoside Ft1, Hypericum perforatum, Shexiang baoxin pills, Naoxintong capsule increased the antiplatelet activity compared with clopidogrel alone, while Danshen decreased the platelet inhibition. In adverse reactions, Danggui can enhance the adverse effects of clopidogrel on the bleeding time. With more awareness and understanding on potential drug-herb interactions of clopidogrel and TCM, it may be possible to combine clopidogrel with TCM herbs to yield a better therapeutic outcome.