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 Aß42-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. Aß42-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.

Molecular Mechanism Analysis of Dengzhan Shengmai Capsules Against Chronic Cerebral Hypoperfusion / 中国实验方剂学杂志

ObjectiveBased on the protective effect of Dengzhan Shengmai capsules （DZSM） on chronic cerebral hypoperfusion （CCH）， network pharmacology was employed to investigate the molecular mechanism. MethodCCH model was established by right common carotid artery ligation. The mice were divided into sham operation group， model group， ginaton group （48 mg·kg-1）， DZSM low- and high-dose groups （0.040 5， 0.162 g·kg-1）. The efficacy was evaluated by the Morris water maze test and open-field test. The underlying mechanism of DZSM for CCH was analyzed by network pharmacology and verified by molecular biology experiments. PubChem， GeneCards， Metascape and other databases were used for targets collection and enrichment analysis. Besides， the association of ingredients targets of DZSM with disease targets of CCH， core target network and chemical components-core targets-pathways network were constructed by STRING 11.0 and Cytoscape 3.7.1. ResultThe escape latency of CCH mice significantly shortened on the 3rd to 5th day after DZSM low-dose treatment， the crossing times， time spent in the target quadrant， movement distance and distance in the central region of CCH mice significantly increased after DZSM low-dose and high-dose treatment. The results of network pharmacology indicated that DZSM might play a key role by regulating inflammatory response， phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway， cytokine-cytokine receptor interaction， tumor necrosis factor （TNF） signaling pathway， blood circulation， angiogenesis， extracellular matrix and other related biological processes and pathways， and acting as targets such as interleukin-6 （IL-6）， TNF， insulin-like growth factor 1 （IGF1）， vascular endothelial growth factor A （VEGFA）， epidermal growth factor （EGF）. The results of biological experiments showed that DZSM could reduce the expression of IL-6 in brain tissue of CCH mice. ConclusionDZSM provides a protective effect during CCH， and its multi-component， multi-pathway， multi-target mechanism is also revealed， which provides a basis for further study of the mechanism.

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<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<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<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<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<0.05). In adverse reactions section, there was no significant difference in the incidence of adverse reactions among the three groups (p>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.

[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.

Research advance in chemical compounds,pharmacological action and clinical application of Dengzhan Shengmai Capsules / 中国中药杂志

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.

Effects of Dengzhan Shengmai Capsule Combined with Isosorbide Mononitrate on Serum MMP- 9，TIMP-1，Blood Lipid Level and Cardiac Function in Patients with Unstable Angina Pectoris / 中国药房

OBJECTIVE： To study the effects of Dengzhan shengmai capsules combined with isosorbide mononitrate on serum TIMP-1 and MMP-9 levels， blood lipid level and cardiac function in patients with unstable angina pectoris （UAP）. METHODS： Totally 198 UAP patients admitted to our hospital from Apr. 2016 to Apr. 2019 were selected， and divided into observation group （n＝102） and control group （n＝96） according to therapy plan. Control group received Isosorbide mononitrate tablets 40 mg， qd， orally； observation group additionally received Dengzhan shengmai capsules， 2 capsules per time， tid， orally， on the basis of control group. Both groups received treatment for consecutive 4 weeks. The clinical efficacy， serum levels of MMP-9 and TIMP-1， blood lipid indexes [low density lipoprotein cholesterol （LDL-C）， high density lipoprotein cholesterol （HDL-C）， triglyceride （TG）， total cholesterol （TC）]， cardiac function indexes [end-diastolic volume （EDV）， left ventricular ejection fraction （LVEF）， end-systolic volume （ESV）] and ADR were compared between 2 groups. RESULTS： The total response rate of observation group was significantly higher than control group （91.18％ vs. 70.83％， P＜0.05）. Before treatment， there was no statistical significance in the levels of ESV， MMP-9， TIMP-1， TC， LDL-C， TG， HDL-C， EDV and LVEF between 2 groups （P＞0.05）. After treatment， the levels of MMP-9， TC， LDL-C， TG， ESV and EDV in 2 groups were decreased significantly in both groups， and the observation group was significantly lower than the control group （P＜0.05）； meanwhile， the levels of TIMP-1， HDL-C and LVEF in 2 groups were increased significantly， and the observation group was significantly higher than control group （P＜0.05）. There was no statistical significance in the incidence of total ADR in 2 groups （P＞0.05）. CONCLUSIONS： Dengzhan shengmai capsules combined with isosorbide mononitrate show good clinical efficacy for UAP， which can effectively reduce serum MMP-9 level and increase serum TIMP-1 level， reduce blood lipid levels， as well as improve cardiac function for UAP patients， with good safety.

Effects of Dengzhan Shengmai Capsules on Autophagy after Cerebral Ischemia-reperfusion in Rats / 中国康复理论与实践

@#Objective To study the effects of Dengzhan Shengmai (DZSM) capsules on the autophagy in brains after cerebral Ischemia-reperfusion in rats. Methods 50 Sprague-Dawley rats were divided into sham group (n=10), 3-methyladenine (3-MA) group (n=10), 3-MA-control group (n=10), DZSM group (n=10) and DZSM-control group (n=10). The middle cerebral arteries were occluded for 1 hour and re-perfused in all the rats except the sham group. The 3-MA and 3-MA-control groups were injected 3-MA or normal saline (NS) into the right lateral ventricle 1 hour before operation. The DZSM and DZSM-control groups accepted DZSM or NS by gavage daily for 3 days since 4 hours after reperfusion. The rats were assessed with Longa's score 3 days after operation, and the expression of microtubule-associated protein 1 light chain 3 (LC3) and Beclin1 in the brain were detected with immunofluorescent labeling and Western blotting; and the level of reactive oxygen species (ROS) were detected with chemiluminescence in the DZSM and DZSM-control groups. Results The expression of LC3 and Beclin1 increased in the ipsilateral ischemic hemisphere, especially in the cortex and striatum surrounding the infarct core (P< 0.001, compared with the sham group). The expression of LC3 and Beclin1 decreased in the 3-MA group compared with the 3-MA-control group (P<0.001), with the decrease of Longa's score (P<0.001). The expression of LC3-II and Beclin1 decreased in the DZSM group compared with the DZSM-control group (P<0.001), with the decrease of Longa's score (P<0.001) and level of ROS (P<0.001). Conclusion Inhibition of autophagy after focal cerebral ischemia-reperfusion plays a role in neuroprotection, which may be a way of DZSM to work.

Effects of Dengzhan Shengmai Capsules on Autophagy after Cerebral Ischemia-reperfusion in Rats / 中国康复理论与实践

Objective To study the effects of Dengzhan Shengmai (DZSM) capsules on the autophagy in brains after cerebral Isch-emia-reperfusion in rats. Methods 50 Sprague-Dawley rats were divided into sham group (n=10), 3-methyladenine (3-MA) group (n=10), 3-MA-control group (n=10), DZSM group (n=10) and DZSM-control group (n=10). The middle cerebral arteries were occluded for 1 hour and re-perfused in all the rats except the sham group. The 3-MA and 3-MA-control groups were injected 3-MA or normal saline (NS) into the right lateral ventricle 1 hour before operation. The DZSM and DZSM-control groups accepted DZSM or NS by gavage daily for 3 days since 4 hours after reperfusion. The rats were assessed with Longa's score 3 days after operation, and the expression of microtubule-associat-ed protein 1 light chain 3 (LC3) and Beclin1 in the brain were detected with immunofluorescent labeling and Western blotting;and the level of reactive oxygen species (ROS) were detected with chemiluminescence in the DZSM and DZSM-control groups. Results The expression of LC3 and Beclin1 increased in the ipsilateral ischemic hemisphere, especially in the cortex and striatum surrounding the infarct core (P<0.001, compared with the sham group). The expression of LC3 and Beclin1 decreased in the 3-MA group compared with the 3-MA-control group (P<0.001), with the decrease of Longa's score (P<0.001). The expression of LC3-II and Beclin1 decreased in the DZSM group com-pared with the DZSM-control group (P<0.001), with the decrease of Longa's score (P<0.001) and level of ROS (P<0.001). Conclusion Inhi-bition of autophagy after focal cerebral ischemia-reperfusion plays a role in neuroprotection, which may be a way of DZSM to work.

Clinical observation of Dengzhan Shengmai Capsules for type 2 diabetes insulin resistance / 中成药

AIM: To observe the clinical efficacy of Dengzhan Shengmai Capsules(Herba Erigerontis,Radix et Rhizoma Ginseng,Radix Ophiopogouis,Fructus Schisandrae chinensis) in improving type 2 diabetes insulin resistance. METHODS: 98 patients were randomly divided into two groups: the control group(50 cases) were treated with conventional therapy,the treatment group(48 cases) were treated with Dengzhan Shengmai Capsules based on conventional therapy.These two groups were all treated for 2 months.FPG,FINS,2hPG,HbA_1C and ISI were observed before and after treatment. RESULTS: The total effects of the treatment group(91.67%) was higher than that of the control group(40.00%)(P