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OBJECTIVE To investigate the effects and mechanism of Danshen decoction influencing platelet physiological characteristics and function in hyperlipidemia model rats based on platelet membrane glycoprotein 4 （CD36）/phosphatidylinositol 3- kinase （PI3K）/protein kinase B （Akt） signaling pathway. METHODS The hyperlipidemia model rats were induced by feeding high- fat diet， and then randomly divided into model group， simvastatin group （0.004 g/kg）， Danshen decoction high-dose and low-dose groups （3.6， 0.9 g/kg）， and blank group （fed with basic feed）， with 10 rats in each group. Rats in each administration group were intragastrically administered with corresponding drugs every day， and the other groups were intragastrically administered with equal volume of normal saline for 4 weeks. After the last administration， the contents of blood lipid biochemical indexes [total cholesterol （TC）， triglyceride （TG）， high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）]， whole blood viscosity， plasma viscosity and fibrinogen （FIB）content in plasma， platelet-related parameters [platelet count （PLT）， platelet distribution width （PDW） and mean plateletvolume （MPV）] were detected. The levels of plateletphysiological characteristics and function-related factors [von Willebrand factor （vWF）， fibronectin （Fn）， phospholipase A2（PLA2）， thromboxane B2 （TXB2）， 6-keto-prostaglandin F1α （6-keto-PGF1α）， thromboxane A2 （TXA2）， prostaglandin I2 （PGI2）， cyclic adenosine monophosphate （cAMP）， cyclic guanosine monophosphate （cGMP）， β-thromboglobulin （β-TG）]， platelet aggregation rate （maximum aggregation rate， 60 s aggregation rate， 180 s aggregation rate） and fibrinolytic system-related factors [tissue plasminogen activator （t-PA）， plasminogen activator inhibitor 1 （PAI-1）] and the expressions of CD36/PI3K/Akt signaling pathway-related proteins [CD36， focal adhesion kinase （FAK）， phosphatidylinositol 4-phosphate 5-kinase （PIP5K）， PI3K， phosphorylated Akt （p-Akt）， p-Akt1/2/3] in platelet were all determined. RESULTS Compared with blank group， the contents of TC， TG and LDL-C in plasma， whole blood viscosity， plasma viscosity， the plasma levels of FIB， PLT， MPV， vWF， Fn， PLA2， TXB2， TXA2， cGMP and β-TG， maximum platelet aggregation rate， 60 s aggregation rate， the expressions of PAI-1 in plasma， protein expressions of CD36， FAK， PIP5K， PI3K， p-Akt and p-Akt1/2/3 were significantly increased in the model group （P＜0.05）. The content of HDL-C and the levels of 6-keto-PGF1α， PGI2 and t-PA were significantly decreased （P＜0.05）. After the intervention of Danshen decoction， most of the above indexes were significantly reversed （P＜0.05）. CONCLUSIONS Danshen decoction can improve the physiological characteristics and function of platelets in hyperlipidemia model rats， and its mechanism may be related to the down-regulation of CD36/PI3K/Akt signaling pathway activity and the reduction of platelet activation.
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Aim To explore the mechanism of Danshen decoction in the treatment of colon cancer using network pharmacology and molecular docking.Methods The active components and corresponding target proteins of Salvia miltiorrhiza, Santalum album and Amo-mum villosum in Danshen decoction were screened based on Traditional Chinese Medicine Systems Pharmacology database and analysis platform.The targets of colon cancer were searched by using Genecards database, and the common targets were selected.The network diagram of traditional Chinese medicine-active components-target-disease was constructed by using Cytoscape 3.7.0.The protein protein interaction network of common targets was constructed by using STRING database.The gene ontology(GO)and Kyoto Encyclopedia of Genes and Gnomes(KEGG)enrichment analysis were carried out based on R4.0.2.The important targets in the key pathways and the important active components in the network diagram of traditional Chinese medicine-active ingredients-target-disease network were selected for Surflex Dock.Results A total of 78 active components, 142 targets, 3 239 colon cancer targets, 105 overlapping targets and 69 corresponding active components were screened out.KEGG analysis showed that the key signaling pathway was PI3K/AKT.Luteolin and Tanshinone IIA with high correlation were selected to dock with protein kinase B(AKT1).Both active components had hydrogen bonding with AKT1.Conclusions Danshen decoction plays a positive role in colon cancer treatment.The mechanism may be related to the regulation of PI3K/AKT signaling pathway.
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Aim To explore the mechanism of Danshen decoction in the treatment of colon cancer using network pharmacology and molecular docking.Methods The active components and corresponding target proteins of Salvia miltiorrhiza, Santalum album and Amo-mum villosum in Danshen decoction were screened based on Traditional Chinese Medicine Systems Pharmacology database and analysis platform.The targets of colon cancer were searched by using Genecards database, and the common targets were selected.The network diagram of traditional Chinese medicine-active components-target-disease was constructed by using Cytoscape 3.7.0.The protein protein interaction network of common targets was constructed by using STRING database.The gene ontology(GO)and Kyoto Encyclopedia of Genes and Gnomes(KEGG)enrichment analysis were carried out based on R4.0.2.The important targets in the key pathways and the important active components in the network diagram of traditional Chinese medicine-active ingredients-target-disease network were selected for Surflex Dock.Results A total of 78 active components, 142 targets, 3 239 colon cancer targets, 105 overlapping targets and 69 corresponding active components were screened out.KEGG analysis showed that the key signaling pathway was PI3K/AKT.Luteolin and Tanshinone IIA with high correlation were selected to dock with protein kinase B(AKT1).Both active components had hydrogen bonding with AKT1.Conclusions Danshen decoction plays a positive role in colon cancer treatment.The mechanism may be related to the regulation of PI3K/AKT signaling pathway.
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Objective Based on the network pharmacology and bioinformatics methods, the networks of active components-targets, protein-protein interactions, and the corresponding biological functions and pathways of key targets were established to predict the molecular mechanism of Danshen Decoction in the treatment of diabetic cardiomyopathy. Methods TCMSP database was used to screen and predict the bioactive components of Danshen Decoction and potential targets. Four databases including PharmGKB were searched for related targets of diabetic cardiomyopathy. The PPI network was constructed for the two types of targets. The key targets were obtained by interactive processing and verified by molecular docking by SystemsDock Web Site. Pathway analysis was performed on the key targets using the DAVID platform (Version 6.8), and the core pathway was screened by Omicshare database and annotated by using Reactome database. Results Taking oral bioavailability (OB) and drug-like (DL) as screening criteria, 78 active ingredients were screened from Danshen Decoction, involving 506 potential targets for treating of diabetic cardiomyopathy. These targets were mainly rich in PI3K-Akt, MAPK and other signaling pathways. Conclusion This study reveals the possible mechanism of Danshen Decoction in the treatment of diabetic cardiomyopathy, embodying the characteristics of multi-component, multi-target and multi-channel of Traditional Chinese Medicine compound, which provides a new idea for further research on its mechanism of action.
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To investigate the inhibitory effect of Huangqi Danshen decoction (HDD) on isoproterenol (ISO)-induced myocardial remodeling and explore its effect on STIM1, TRPC1, CaN and NFATc3 expressions. ISO (2.5 mg•kg⁻¹•d⁻¹×14 d) was given by subcutaneous injection to establish myocardial remodeling models in rats, and then were randomly divided into control group, ISO model group, HDD5 group (HDD 5 g•kg⁻¹•d⁻¹+ISO), and HDD10 group (HDD 10 g•kg⁻¹•d⁻¹+ISO). After intervention for 4 weeks, the heart mass index (HW/BW) and the left ventricular mass index (LVW/BW) were calculated; the structure of myocardium was observed by echocardiography; the pathological changes of myocardium were observed by HE staining; levels of BNP, CaN and CaM kinases II in serum were detected by ELISA, and the protein expression levels of STIM1, TRPC1, p-CaN, p-NFATc3, and NFATc3 in left ventricular tissues were detected by Western blot. The results showed that the HW/BW and LVW/BW in ISO group were greater than those in HDD5 group and HDD10 group (P<0.05); Echocardiography showed that HDD inhibited ISO-induced increase in LVEDD and LVESD; ELISA results showed that HDD could significantly inhibit the increase of BNP, CaN and CaM kinases II levels in serum of rats with ISO-induced myocardial remodeling (P<0.01). Western blot results showed that STIM1, TRPC1, p-CaN, p-NFATc3 and NFATc3 expression levels were increased in the myocardial tissues of ISO group rats, and after HDD administration, the above expression levels were decreased in group ISO, HDD for myocardial tissue after administration of STIM1, TRPC1, p-CaN, p-NFATc3 and NFATc3 expression decreased (P<0.05). Our findings indicated that HDD can attenuate the myocardial remodeling induced by ISO, and its mechanism may be related to down-regulating the expression levels of STIM1, TRPC1, CaM kinases II, p-CaN/CaN and p-NFATc3/NFATc3.
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Objective To explore the effect of heating temperature and heating time on the dissolution characteristics of phenolic acids in water extract of Danshen Decoction. Methods The contents of tanshinol, protocatechuic aldehyde and salvianolic acid B in water extract of Danshen Decoction were determined by reverse-phase high performance liquid chromatography (RP-HPLC) . The changes of the contents were monitored by classic constant temperature acceleration method. Results Of the three components, the content of salvianolic acid was decreased with the increase of heating temperature and the prolongation of heating time, and the degradation characteristics of the salvianolic acid B met the first-order kinetics equation. Conclusion The water-soluble components have less stability in the water extracts of Danshen Decoction. Lignum Santali Albi and Fructus Amomi accelerate the degradation speed of Radix Salviae Miltiorrhizae, suggesting that we should pay attention to the influence of heating temperature and heating time on the content of salvianolic acid B in the extraction and concentration process.
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Objective To investigate the effects of Jiawei Danshen Decoction on endothelial cell ultrastructure, serum NO and ET in apolipoprotein E-knockout atherosclerosis (AS) mice;To discuss its mechanism of anti-atherosclerosis.Methods Totally 24 7-8 weeks old ApoE -/- mice were fed with a high fat diet for 12 weeks until the a mature atherosclerotic plaque was formed. They were randomly divided into four groups:model group, control group,Jiawei Danshen Decoction of low-dose group and high-dose group, 6 mice in each group. Another 6 normal C57BL/6J mice with the same strain were set as the blank group, and fed with general diet. After medicine intervention by gavage for 8 weeks, blood was extracted from orbital venous to measure serum NO and ET;aortic endothelial cell ultrastructure changes were observed by transmission electron microscope.Results Compared with the blank group, the level of NO obviously decreased and ET significantly increased in the model group (P<0.01). Compared with model group, medicine intervention increased NO and reduce ET level (P<0.05). Electron microscopy results showed that the model group showed fatty streaks stage performance;endothelial damage in each administration group was improved compared with model group.Conclusion Jiawei Danshen Decoction can improve the endothelial cell ultrastructure and functions and protect endothelial cells, with a purpose to delay the AS process.
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Objective: To carry out the pharmacokinetic study in awake animal after multiple dosing of Danshen (Salvia miltiorrhiza) Decoction by blood microdialysis method combined with LC-MS. Methods: The pharmacokinetic study was carried out with awake rabbits as experimental animal, Danshen Decoction as tool drug, and Danshensu as evaluation index combining with microdialysis sampling and LC-MS detection technology after intraday multiple dosing. The pharmacokinetic parameters were obtained by non-compartmental model method. Results: The pharmacokinetic study pattern of multiple dosing was established in awake animal, and the whole process dynamic characteristics were collected. The method was stable, reliable, and simple. Conclusion: This study can make the reference to similar study for other drugs.
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@#ObjectiveTo observe the effect of Huanglian Wendan decoction and Danshen decoction combined with Wester medicineon stable coronary heart disease.Methods60 patients with angina or myocardial infarction were randomly divided into the control group and treatment group with 30 cases in each group. The patients of the control group were treated with routine medicine and those of the treatment group were added with traditional Chinese medicine (TCM) Huanglian Wendan decoction combined with Danshen decoction. The changes of angina, symptoms and signs of TCM, electrocardiogram (ECG), low density lipoprotein cholesterol (LDL-C) and high sensitive C-reactive protein (HS-CRP) of all patients were observed before and after treatment.ResultsAfter treatment, the frequency and duration of angina, dose of notroglycerine of patients in two groups were significantly different from those before treatment (P<0.01 ), but there was no significant difference between two groups (P>0.05). The symptoms such as chest discomfort and palpitation of patients of two groups improved after treatment (P<0.05～0.01), but the treatment group improved more obviously than the control group (P<0.05). The total effective rate showed by ECG were 53.3% in the control group and 73.3 % in the treatment group, there was no significant difference between two groups. HS-CRP and LDL-C of all patients decreased after treatment (P<0.01), but the treatment group was lower than the control group (P<0.05).Conclusion Huanglian Wendan decoction combined with Danshen decoction can relief clinical symptoms of stable coronary heart disease, which may be related with lipid decrease and inflammation reduction.
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0.05).EGF expression in the gastric juice and EGFR expression level in the gastric mucosa were increased in the two treatment groups after treatment(P