Novel strategy in Dengzhan Shengmai capsule metabolites analysis based on the prediction database / 药学学报

Dengzhan Shengmai capsule, as a compound Chinese patent medicine, consists of four herbs: Herba Erigerontis, Ginseng, Ophiopogon, and Schisandrae Chinensis Fructus, and contains significant components of flavonoids, lignans, saponins, and organic acids. It is widely used clinically to treat cerebrovascular diseases such as chronic cerebral hypoperfusion and dementia with remarkable efficacy. This study proposes a research strategy for multi-component traditional Chinese medicine metabolites based on prediction databases and unfolds the analysis using Dengzhan Shengmai capsule as an example. Using the UPLC-Q-TOF/MS method, the analytical method was established and detected biological samples such as urine, feces, and bile of rats before and after administration based on the prediction of theoretical metabolites of Dengzhan Shengmai capsule. The possible secondary fragment ion information of metabolites was identified by comparing the detected results with prediction databases. The metabolites were identified based on the archetypal component mass spectrometric cleavage law and multistage mass spectrometric data. 51 metabolites, mainly flavonoid, organic acid, and lignan constituents, were finally identified from rat biosamples based on 306 theoretical metabolites of Dengzhan Shengmai capsule. This study provides a new strategy for the identification of metabolites in vivo and the analysis of metabolic pathways of TCM. The study complied with the procedures established by the Animal Experiment Ethics Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences and passed the animal experiment ethics examine (No. 00003645).

Dengzhan Shengmai inhibits nonalcoholic fatty liver disease via regulating intestinal microenvironment / 药学学报

The aim of this study was to investigate the efficacy and mechanism of Dengzhan Shengmai (DZSM) against nonalcoholic fatty liver diseases (NAFLD). The animal experiment program was reviewed and approved by the Ethics Committee of Institute of Materia Medica, Chinese Academy of Medical Sciences. The NAFLD model of Syrian golden hamsters was established by high fat diets. After 6 weeks of DZSM treatment, the serum lipid, hepatic lipid accumulation, liver function and inflammatory response were determined. The regulations of gut microbiota and short-chain fatty acids were detected by 16S rRNA gene sequencing and gas chromatography-mass spectrometry method, respectively. The gut barrier function was evaluated by enzyme linked immunosorbent assay (ELISA), reverse transcription-quantitative polymerase chain reaction (RT-qPCR), Western blot and histopathological methods and further verified in HepG2 cells. The results showed that the efficacy of DZSM against NAFLD was remarkably reduced after removal of the gut microbiota. The study of mechanism showed that DZSM significantly regulated the composition of gut microbiota, promoted the production and absorption of intestinal short-chain fatty acids, then leading to the reduction of hepatic lipid accumulation. Moreover, after DZSM treatment, the decreased lipopolysaccharide (LPS) level by improving the intestinal barrier function significantly inhibited the hepatic inflammation through down-regulating Toll like receptor 4 (TLR4)-nuclear factor kappa B (NFKB) signaling pathway. These results indicate that DZSM inhibits NAFLD via regulating intestinal microenvironment.

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 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.

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.

Neuroprotective effect of Dengzhan Shengmai capsule on ischemia/reperfusion injury in rats / 实用医学杂志

Objective To investigate the neuroprotective effect of Dengzhan Shengmai capsule (DZSM) in rat cerebral ischemia-reperfusion injury and to explore the mechanism. Methods Rats were divided into Sham group, MCAO group, DZSM group, carbenoxolone (CBX) group and DZSM + CBX group. Each group was assessed for neurological function , infarct volume and the expression of Caspase-3 48 h after reperfusion. Connexin 43 (Cx43) expression of MCAO group was detected 3, 12, 24, 48 h after reperfusion. Results There were lower neurological deficit scores , infarct volume and the expression of Caspase-3 in DZSM , CBX and DZSM + CBX group 48 h after reperfusion when compared with those in MCAO group (P < 0.05) but Cx43 expression level in each group increased after reperfusion at each time point (P < 0.05). Expression of Cx43 was lower in DZSM, CBX and DZSM + CBX group than that in MCAO group (P < 0.05). Lower expression of Cx43 was also seen in CBX and DZSM + CBX group when compared with that in DZSM group (P < 0.05). Conclusion DZSM capsule can improve neurological function , reduce infarct volume and inhibit the expression of Caspase-3. The mechanism may be related to its inhibition of Cx43 expression.

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.

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 capsule on renovascular hypertension-induced β-amyloid protein deposition and cognitive impairment in rats / 中华行为医学与脑科学杂志

Objective To observe the effects of Dengzhan Shengmai capsule on β-amyloid protein (Aβ) deposition in the brain and learning and memory function in renovascular hypertensive rats (RHRSP).Methods Male Sprague-Dawley rats were randomly divided into four groups (5 rats per group):normal group,shamoperated group,hypertension with Dengzhan Shengmai capsule treatment group and hypertension with normal saline (NS) treatment group.Renovascular hypertensive models were created by clipping two-kidney.Dengzhan Shengmai capsules were dissolved in sterile 0.9％ NS and were administered (20 mg · kg-1 per day) by daily gavage for 4 weeks.In the NS group,hypertensive rats were given saline in the same volume.Immunofluorescent labeling and western blot were used to detect the expression of Aβ,NF-κB,IL-1β,TNF-α in the brain,respectively.Learning and memory function were detected by Morris water maze.Results RHRSP significantly increased Aβ deposition in the cerebral cortex and impaired memory function in rats.Dengzhan Shengmai capsule treatment significantly lowered the blood pressure compared with NS treatment((157.45±11.58) mmHgvs (197.76±10.12) mmHg).In addition,the levels of Aβ,NF-κB p65,IL-1β,TNF-α protein were significantly reduced,by Dengzhan Shengmai caspule treatment.The escape latency was shortened((24.64±4.57) s vs (37.17±3.87)s),while the frequency of passing through the platform quadrant(5.39±0.12 vs 3.05±0.28) and the dwell time((27.34±3.67) s vs (16.83±5.76)s) (all P＜0.01) in the platform quadrant were significantly increased by Dengzhan Shengmai capsule treatment.Conclusions Dengzhan Shengmai capsule may reduce Aβ deposition in brain and improve learning and memory function by anti-inflammatory effects in RHRSP.

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