OBJECTIVE Xiao-xu-ming decoction(XXMD),a well-known traditional Chinese herbal prescription,has been widely used to treat stroke.It is recorded in″Bei Ji Qian Jin Yao Fang″written by Si-miao Sun of the Chinese ancie...OBJECTIVE Xiao-xu-ming decoction(XXMD),a well-known traditional Chinese herbal prescription,has been widely used to treat stroke.It is recorded in″Bei Ji Qian Jin Yao Fang″written by Si-miao Sun of the Chinese ancient Tang Dynasty.In our previous study,the active fraction of XXMD(XXM)against cerebral ischemia has been prepared by modern separation and purification techniques.This study was to investigate XXM against lipopolysaccaride(LPS)-induced neuroinflammation in mice.METHODS LPS is an endotoxin from the outer membrane of Gram-negative bacteria that activates inflammation.XXM was pre-treated in BALB/C mice followed by injected intraperitoneally with LPS(5 mg·kg-1).The effects of XXM on LPS-induced pro-inflammatory factors and proteins were measured by ELISA,Western blot,and immunofluorescence in vivo.RESULTS Mice treated with XXM showed significantly decreased proinflammatory factors level,including IL-1β(P<0.01),IL-6(P<0.01),TNF-α(P<0.05),and MCP-1(P<0.01).Furthermore,XXM also significantly inhibited the inflammatory pathway proteins expression induced by LPS,including TLR4,MyD 88,and COX-2.CONCLUSION XXM possesses anti-neuroinflammation in mice and might be a promising therapeutic agent for stroke.展开更多
OBJECTIVE Using bioinformatics methods,to establish Xiao-Xu-Ming decoction(XX.MD) "compound-vasoconstriction G Protein-Coupled Receptors(GPCR) targets" network,and analyze the vasoconstriction regulatory eff...OBJECTIVE Using bioinformatics methods,to establish Xiao-Xu-Ming decoction(XX.MD) "compound-vasoconstriction G Protein-Coupled Receptors(GPCR) targets" network,and analyze the vasoconstriction regulatory effective components and the potential targets of XXMD.METHODS Ac.cording to the XXMD herb sources,we retrieved the chemical structures from the national scientific da.ta sharing platform for population and health pharmaceutical information center,TCMSP database and the latest research literature.The chemical molecular library was established after class prediction and screening for medicinal and metabolic properties.Five kinds of vasoconstriction GPCR crystal structure including 5-HT receptors(5-HT1 AR,5-HT1 BR),AT1 R,β2-AR,hUTR and ETB were retrieved from Bank Pro.tein Data Bank database or homology modeling using Discovery Studio 4.1 built-in modeling tools.After virtual screening by Libdock molecular docking,the highest rated 50 compounds of each target were col.lected and analyzed.The collected data were further used to construct and analyze the network.RE.SULTS 859 single compound structures information in XXMD were generalized following the screen.ing of obtained 2043 compounds.The complicated compound-vasoconstriction GPCR targets network of XXMD was then constructed and analyzed by molecular docking with the above five kinds of GPCR target receptors.Most of the chemical composition effects were associated with different vasoconstric.tion GPCR targets,while a few effective components can be applied to multiple GPCR targets at the same time,therefore forming synergies.CONCLUSION Vasorelaxant effects of XXMD may not only result from the collaborative interaction between a variety of active ingredients in Chinese medicine and multi.ple targets,but also from the interaction between some effective component and multiple targets.展开更多
OBJECTIVE Vascular dementia(VD) refers to a progressive decline in memory and cognitive function caused by chronic cerebral ischemia.2-Vessels occlusion(2-VO) has been widely used as a model of VD.Xiao-Xu-Ming decocti...OBJECTIVE Vascular dementia(VD) refers to a progressive decline in memory and cognitive function caused by chronic cerebral ischemia.2-Vessels occlusion(2-VO) has been widely used as a model of VD.Xiao-Xu-Ming decoction,a well-known traditional Chinese medicine prescrip.tion,has been widely used to treat stroke and sequelae of stroke.The present study was to investigate the mechanism of Xiao-Xu-Ming decoction(XXM) against chronic cerebral ischemia injury in rats.METHODS After XXM treatment,rats were performed a memory testing with Morris water maze and motor ability testing using prehensile test and inclined screen test.Neuronal plasticity was observed by immunofluorescent staining with MAP2 antibody.Differentially expressed proteins of rat hippocampus were analyzed by Label-free quantitative proteomics.RESULTS XXM significantly alleviated 2-VOinduced learning and memory deficits,motor ability dysfunction,and neuronal plasticity injury in rats.The mechanism might be involved in up-regulation of 39 proteins and down-regulation of 13 proteins in the hippocampus of rats after XXM treatment vs 2-VO group rats.Gene ontology and pathway analysis showed that the regulated proteins are mainly involved in oxidation reduction process,intracellular signaling cascade process,and protein catabolic process,etc.The signal pathways are mainly involved in ubiquitin mediated proteolysis and phosphatidylinositol signaling system.CONCLUSION Current findings provide new insights into the molecular mechanisms of XXM on chronic cerebral ischemia.展开更多
OBJECTIVE To investigate the cerebralvasorelaxant material basis of Xiaoxuming decoction.METHODS According to the Xiaoxuming decoction herb sources,we retrieved the chemical structure from the literatures and the Chin...OBJECTIVE To investigate the cerebralvasorelaxant material basis of Xiaoxuming decoction.METHODS According to the Xiaoxuming decoction herb sources,we retrieved the chemical structure from the literatures and the Chinese Natural Product Database(http://pharmdata.ncmi.cn).By using microvessel tension system,we checked the vasorelaxanteffects of Xiaoxuming decoction anti-cerebral ischemia effective components group(XXMDECG)and the available composition compounds on pre-contracted basilar artery ring.RESULTS963 compoundsin the decoction,including 81Fangfeng,77 Mahuang,130 Shengjiang,31 Guizhi,91 Huangqin,127 Renshen,73 Chuanxiong,44 Shaoyao,39 Xingren,42 Fangji,62 Fuzi and 166 Gancao were collected.The five largest number classes of compounds in the decoction are volatile oil(32%),flavone(32%),alkaloid(13%),saponin(7%),polyphenol and organic acid(5%).XXMDECG at concentration from 1 to 400μg·mL-1can dilate the KCl(60 mmol·L-1)and ET-1(0.01μmol·L-1)pre-contracted rat basilar artery rings in a dose-dependent manner.There are 6 compounds with vasorelaxant ratio more than 50%at the concentration of 10μmol·L-1.CONCLUSION Xiaoxuming decoction contains abundant chemical structure.It has the material basis of multiple ingredients and multiple targets.The XXMDECG are able to dilate the rat basilar artery rings in a dose-dependent manner.The network interactions between varies of chemical compounds in Xiaoxuming decoction and the vasoconstriction associated targets result in the comprehensive regulation mechanisms of vascular function.展开更多
OBJECTIVE Cranial radiotherapy is clinically used in the treatment of brain tumors;however,the consequent cognitive and emotional dysfunctions seriously impair the life quality of patients.LW-AFC,an active fraction co...OBJECTIVE Cranial radiotherapy is clinically used in the treatment of brain tumors;however,the consequent cognitive and emotional dysfunctions seriously impair the life quality of patients.LW-AFC,an active fraction combination extracted from classical traditional Chinese medicine prescription Liuwei Dihuang decoction,can improve cognitive and emotional dysfunctions in many animal models;however,the protective effect of LW-AFC on cranial irradiation-induced cognitive and emotional dysfunctions has not been reported.Recent studies indicate that impairment of adult hippocampal neurogenesis(AHN)and alterations of the neurogenic microenvironment in the hippocampus constitute critical factors in cognitive and emotional dysfunctions following cranial irradiation.Here,our research further investigated the potential protective effects and mechanisms of LW-AFC on cranial irradiation-induced cognitive and emotional dysfunctions in mice.METHODS LW-AFC(1.6 g·kg^(-1))was intragastrically administered to mice for 14 d before cranial irradiation(7 Gyγ-ray).AHN was examined by quantifying the number of proliferative neural stem cells and immature neurons in the dorsal and ventral hippocampus.The contextual fear conditioning test,open field test,and tail suspension test were used to assess cognitive and emotional functions in mice.To detect the change of the neurogenic microenvironment,colorimetry and multiplex bead analysis were performed to measure the level of oxidative stress,neurotrophic and growth factors,and inflammation in the hippocampus.RESULTS LW-AFC exerted beneficial effects on the contextual fear memory,anxiety behavior,and depression behavior in irradiated mice.Moreover,LW-AFC increased the number of proliferative neural stem cells and immature neurons in the dorsal hippocampus,displaying a regional specificity of neurogenic response.For the neurogenic microenvironment,LW-AFC significantly increased the contents of superoxide dismutase,glutathione peroxidase,glutathione,and catalase and decreased the content of malondialdehyde in the hippocampus of irradiated mice,accompanied by the increase in brain-derived neurotrophic factor,insulin-like growth factor-1,and interleukin-4 content.Together,LW-AFC improved cognitive and emotional dysfunctions,promoted AHN preferentially in the dorsal hippocampus,and ameliorated disturbance in the neurogenic microenvironment in irradiated mice.CONCLUSION LW-AFC ameliorates cranial irradiation-induced cognitive and emotional dysfunctions,and the underlying mechanisms are mediated by promoting AHN in the dorsal hippocampus and improving the neurogenic microenvironment.LW-AFC might be a promising therapeutic agent to treat cognitive and emotional dysfunctions in patients receiving cranial radiotherapy.展开更多
OBJECTIVE To investigate age-related functional change of hypothalamus-pituitary-adrenal(HPA)axis in senescence accelerated mouse(SAM)and the effects of Liuwei Dihuang decoction(LW)and its San-bu(three tonics)and San-...OBJECTIVE To investigate age-related functional change of hypothalamus-pituitary-adrenal(HPA)axis in senescence accelerated mouse(SAM)and the effects of Liuwei Dihuang decoction(LW)and its San-bu(three tonics)and San-xie(three eliminators)components on the function of HPA axis.METHODS Male SAM-resistance/1(SAMR1)and SAM-prone/8(SAMP8)at the ages of 6and 12 months old were used.SAMP8 were orally administered with LW,three tonics and three eliminators at the doses of 10,6.4and 3.6g·kg-1·d-1,respectively,for consecutive 60 d.Serum level of CORT was assayed with ELISA method.The levels of hypothalamic CRH and pituitary ACTH was determined with radioimmunoassay.RESULTS The levels of hypothalamic CRH,pituitary ACTH and serous CORT were much higher in 6 and 12 months old SAMP8 than those in age-matched SAMR1,which suggested the abnormal function of HPA axis in SAMP8.Oral administration of LW and three tonics significantly decreased the level of hypothalamic CRH of 6 and 12 months old SAMP8,and reduced the levels of pituitary ACTH and serous CORT of 6 month old SAMP8.Three eliminators significantly decreased the level of hypothalamic CRH of 6 months old SAMP8.The results indicated that oral administration of LW,three tonics and three eliminators improved the function of HPA axis of SAMP8.CONCLUSION The results showed the hyperactivity of HPA axis of SAMP8,and LW improved the hyperactivity of 6 month old SAMP8.Three tonics and three eliminators had similar effects as LW,which had better effect after compatibility.展开更多
OBJECTIVE To screen the active ingredients preventing platelet aggregations from Taohong Siwu Decoction. METHODS Fresh blood from healthy adult volunteer was collected with vacuum tube for preparation of platelet susp...OBJECTIVE To screen the active ingredients preventing platelet aggregations from Taohong Siwu Decoction. METHODS Fresh blood from healthy adult volunteer was collected with vacuum tube for preparation of platelet suspension. Platelet suspension was incubated with Taohong Siwu Decoction for one hour at 37℃,then centrifuged. The precipitate was washed and desorbed with buffer solutions.The differences of chemical constituents between incubated and unincubated were identified with high performance liquid chromatography-diode array detector. RESULTS According to the chromatograph at 254 nm,at least three kinds of different components were detected in Taohong siwu decoction before and after incubated with platelet. CONCLUSION Platelet suspension can be used for screening active ingredients on platelet membrane receptor from the traditional Chinese medicine.展开更多
OBJECTIVE To investigate the effects of LW-AFC,a new formula derived fromLiuwei Dihuang decoction,on gut microbiota and the behavior of learning and memory of SAMP8 mice,a mouse model of Alzheimer Disease(AD),and iden...OBJECTIVE To investigate the effects of LW-AFC,a new formula derived fromLiuwei Dihuang decoction,on gut microbiota and the behavior of learning and memory of SAMP8 mice,a mouse model of Alzheimer Disease(AD),and identify the specific intestinal microbiota correlating with cognitive ability.METHODS Morris-water maze test,novel object recognition test and shuttle-box test were conducted to observe the ability of learning and memory.16S rRNA amplicon sequencing(Illumina,San Diego,CA,USA)was employed to investigate gut microbiota.RESULTS The treatment of LW-AFC improved cognitive impairments of SAMP8 mice,including spatial learning and memory ability,active avoidance response,and object recognition memory capability.Our data indicated that there were significantly 8 increased and 12 decreased operational taxonomic units(OTUs)in the gut microbiota of SAMP8 mice compared with senescence accelerated mouse resistant 1(SAMR1) strains,the control of SAMP8 mice.The treatment of LW-AFC altered 22(16 increased and 6 decreased)OTUs in SAMP8 mice and among them,15 OTUs could be reversed by LW-AFC treatment resulting in a microbial composition similar to that of SAMR1 mice.We further showed that there were7(3 negative and 4 positive correlation)OTUs significantly correlated with all the three types of cognitive abilities,at the order level,including Bacteroidales,Clostridiales,Desulfovibrionales,CW040,and two unclassified orders.LW-AFC had influences on bacterial taxa correlated with the abilities of learning and memory in SAMP8 mice and restored them to SAMR1 mice.CONCLUSION The effects of LW-AFC on improving cognitive impairments of SAMP8 mice might be via modulating intestinal microbiome and LW-AFC could be used as a potential anti-AD agent.展开更多
OBJECTIVE Cisplatin is a formidable chemotherapy agent widely applying in antineoplastic treatments,but its side effects often limit the clinical usage.Metabolic disorders are one of the side effects induced by cispla...OBJECTIVE Cisplatin is a formidable chemotherapy agent widely applying in antineoplastic treatments,but its side effects often limit the clinical usage.Metabolic disorders are one of the side effects induced by cisplatin,which closely relate to the onset of chemotherapy-induced anorexia(CIA)in cancer patients but lacks effective controls.Liujunzi decoction(LJZD)is a traditional Chinese formula that has a promising effect in treating CIA.However,whether LJZD ameliorates CIA through adjusting cisplatin-induced metabolic disorders remain unknow.The present study evaluated the mechanism of cisplatin-induced metabolic disorders,and the effect of LJZD in ameliorating these disturbances.METHODS 42 male Sprague-Dawley(SD)rats(180-220 g)were randomly divided into 3 groups:normal control group(distilled water+saline),model group(distilled water+cisplatin),LJZD group(4.8 g·kg^(-1)Liujunzi decoction ingredients+cisplatin).Intragastrical administered each drug twice a day(7∶00-19∶00)since day 0 for 4 d,animals were intraperitoneal injected with cisplatin 6 mg·kg^(-1)1 h after administration while normal control groups were injected with same volume of saline.On day 3,each group was anesthetized with pentobarbital sodium 45 mg·kg^(-1)(ip),and blood samples were collected from aorta abdominalis.Then the samples were analyzed using an LC-ESI-MS/MS system.Significantly regulated metabolites between groups were determined by VIP≥1 and absolute Log2FC(fold change)≥1.Identified metabolites were mapped to Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway database using Metaboanalyst 5.0(https://www.metaboanalyst.ca/).RESULTS A total of 133,77 and 32 differential metabolites were filtrated in control vs model,control vs LJZD and model vs LJZD groups respectively.Comparing to control,the levels of hexadecanoic acid(Log2FC=6.3153),linoleic acid(Log2FC=5.3478),and 8,11-icosadienoic acid(Log2FC=5.2342)significantly increased,and the levels of N-acetyl-L-tyrosine(Log2FC=-2.6283),cinnamic acid(Log2FC=-2.3381),N-acetylphenylalanine(Log2FC=-2.2501)significantly decreased in model group.The KEGG pathway enrichments of these metabolites indicated that,cisplatin-induced metabolic disorders by disturbing metabolism pathways such as linoleic acid metabolism,biosynthesis of unsaturated fatty acids,and phenylalanine metabolism,which suggested that the onset of CIA was partly associated with the metabolic disorders of linoleic acid,unsaturated fatty acids,and phenylalanine.Compared to control,treatment of LJZD significantly increased the levels of 4-hydroxytryptamine(Log2FC=12.0186),hexadecanoic acid(Log2FC=5.7412),linoleic acid(Log2FC=5.1877)and significantly decreased the levels of N-acetylmethionine(Log2FC=-1.7317),2-aminoethanesulfinic acid(Log2FC=-1.6578),N-acetyl-L-tyrosine(Log2FC=-1.5355).And comparing to the model group,4-hydroxytryptamine(Log2FC=12.0186),7,12-diketocholic acid(Log2FC=2.0998),N-acetylneuraminic acid(Log2FC=2.0560)markedly increased,and 3-hydroxy-3-methylpentane-1(Log2FC=-1.9202),5-dioic acid(Log2FC=-1.7166),N-isovaleroylglycine,hexanoyl glycine(Log2FC=-1.4958)markedly decreased in LJZD group.It was worth noting that,there were 23 differential metabolites filtrated both in control vs model and model vs LJZD groups,which were the key metabolites of LJZD in treating CIA.Among these 23 common metabolites,there were 16 metabolites excluding the control vs LJZD group,that was,LJZD had no effect in normal rats while being able to ameliorated cisplatin-induced metabolic disorders by regulating these 16 metabolites.Cisplatin-induced downregulation of 11 metabolites such as hydrocinnamic acid,(±)12(13)epoxy-9Z-octadecenoic acid,cinnamic acid were upregulated after LJZD treatment,and cisplatin-induced upregulation of imidazoleacetic acid,2′-deoxycytidine-5′-monophosphate and other 5 metabolites were downregulated by LJZD.The KEGG pathway analysis indicated that the linoleic acid metabolism,histidine metabolism,and pyrimidine metabolism were the most enriched metabolic pathway.Thus,cisplatin-induced metabolic disturbances mainly by disturbing linoleic acid metabolism,histidine metabolism,and pyrimidine metabolism,and LJZD interacted with these metabolic pathways to reduce metabolic disorders and thus ameliorated CIA.CONCLUSION Cisplatin-induced anorexia was closely related to the metabolic disorders of linoleic acid metabolism,biosynthesis of unsaturated fatty acids,and phenylalanine metabolism.The mechanism of LJZD in ameliorating CIA was in concerned with the metabolic adjustments,relating to the regulation of linoleic acid metabolism,histidine metabolism,and pyrimidine metabolism.展开更多
OBJECTIVE To investigate the effects of Huanglian Jiedu decoction on cognitive dysfunction of zebrafish with Alzheimer disease.METHODS 126 g of coptis chinensis,84 g of phellorescent phellorescent chinensis,84 g of sc...OBJECTIVE To investigate the effects of Huanglian Jiedu decoction on cognitive dysfunction of zebrafish with Alzheimer disease.METHODS 126 g of coptis chinensis,84 g of phellorescent phellorescent chinensis,84 g of scutellaria chinensis and 126 g of gardenia chinensis were immersed in 10,8 and 8 times of water for 30 min,and then extracted at 100℃for 2,1.5 and 1.5 h,respectively.The three extracts were coarse filtered and concentrated into 308 g·L-1 and stored in refrigerator for later use.200 zebrafish were selected for behavioral train⁃ing in T-shaped tank for seven days.After that,the behavioral record analysis software Smart 3.0 was used to conduct behavioral analysis.Qualified zebrafish were selected as the blank group.Except for the blank group,zebrafish in the other 5 groups were exposed to AlCl3100μg·L-1 aquaculture water for modeling,and exposed for 6 d.The behavioral record analysis software Smart 3.0 was used to conduct behavioral analysis,and Select the successfully modeled zebraf⁃ish.After that,huperzine A(4μg·L-1)and Huan⁃glian Jiedu decoction of low,medium and high doses(154,308 and 616 mg·L-1)were adminis⁃tered respectively,and exposed for six days.Then,the behavior analysis was conducted again through the behavioral record analysis soft⁃ware Smart 3.0 to select qualified zebrafish.After the training,the brain and gut of zebrafish in each group were collected,and the expression changes of N-cadherin,p-P38/p38MAPK and p-Tau in the brain were detected by Western blot⁃ting and qPCR to show the effect of Huanglian Jiedu decoction on cognitive dysfunction of Zebrafish with Alzheimer disease.RESULTS Western blotting and qPCR results showed that the contents of N-cadherin increased(P<0.05),and the contents of p-P38/p38MAPK and p-Tau decreased(P<0.05)compared with the model group,indicating that Huanglian Jiadu decoction had an effect on the cognitive dysfunction of zebrafish with Alzheimer disease.CONCLU⁃SION Huanglian Jiedu decoction can alleviate cognitive dysfunction of zebrafish model with Alzheimer disease to a certain extent.展开更多
Aim This work is to provide a network approach to identify the potential therapeutic targets in molecular level for xuefu-zhuyu decoction （XZD） and gualou-xiebai-banxia decoction （GXBD） in treating Coronary artery...Aim This work is to provide a network approach to identify the potential therapeutic targets in molecular level for xuefu-zhuyu decoction （XZD） and gualou-xiebai-banxia decoction （GXBD） in treating Coronary artery dis- ease （CAD）. Methods The networks between the ingredients/drugs and relevant target proteins for XZD, GXBD, and modern anti-CAD drugs were constructed, respectively. A master network based on the three established networks was further generated. By comparing the similarities and the differences of the targets containing in the master net- work between the individual formula and the modern drugs, the potential anti-CAD targets for XZD and GXBD were i- dentified for further pharmacological investigations. Results Although the herbal formulations and the chemical con- stituents of XZD and GXBD were significant different, both formulas presented the great similarity on target proteins and with the Tanimoto coefficient of 0. 7225. Comparison the formula-specific targets to modem drugs targets, 50 mu- tual targets with higher possibility were modulated. Moreover, a total amount of 114 mutual targets between formulas derived from the master network were identified to be not yet related to those of the approved anti-CAD drugs. Among them, the top 10 targets were identified to be NOS3, PTPN1, GABRA1, PRKACA, CDK2, MAOB, ESR1, ADH1C, ADH1B and AKR1B1. The formula-specific targets of XZD or GXBD which were not yet covered by the current anti- CAD drugs provided the potential opportunities to discovery of the new drug candidates from the two formulas for CAD treatment. Conclusion The established method of network analysis provides a novel approach for screening of the potential therapeutic targets based on the chemical constituents in traditional Chinese medicines or formulas. It is cru- cial for this work to select relatively favorable therapeutic areas of traditional Chinese medicines, syndrome-oriented formulas and syndrome differentiation of same diseases. Meanwhile, this kind of work is helpful for unveiling the mo- lecular mechanism of TCM formulas.展开更多
Objective Study on the effect of NF-κB in ox-LDL injured HUVEC-304 and the intervention with the serum of Tongmai Decoction. Methods Tongmai Decoction herbage-contained serum was made by the serum pharmacology method...Objective Study on the effect of NF-κB in ox-LDL injured HUVEC-304 and the intervention with the serum of Tongmai Decoction. Methods Tongmai Decoction herbage-contained serum was made by the serum pharmacology methods, then the HUVEC-304 cells were divided into 5 groups and incubated for 24 h: 1) normal group;2) fetal calf serum group; 3) ox-LDL group; 4) simvastatin group; 5) Tongmai Decoction group. RT-PCR was used to determine the mRNA of NF-κB in the cells, Western Blot Assay was used to determine the protein content of NF-κB in the cells. Results 1) Compared with the cells in normal group and serum control group , the endothelial cells in ox-LDL group are seriously injured, while those in Tongmai Decoction group grow better; 2) Compared with the cells in normal group and fetal calf serum group, the expressions of NF-κB gene and protein are up-regulated in ox-LDL group(P＜0.05, P＜0.01); 3) Compared with the cells in ox-LDL group, the expression of NF-κB gene and protein in Tongmai Decoction group are significantly down-regulated, there is no difference between Tongmai Decoction group and simvastatin group(P＞0.05). Conclusion Tongmai Decoction can protect the injured endothelial cells, up-regulate the expressions of NF-κB gene and protein content.展开更多
OBJECTIVE To explore the curative effect and mechanism of Yiqi Huoxue decoction in the treatment of coronary heart disease with Qi deficiency and blood stasis syndrome.METHODS The patients with coronary heart disease ...OBJECTIVE To explore the curative effect and mechanism of Yiqi Huoxue decoction in the treatment of coronary heart disease with Qi deficiency and blood stasis syndrome.METHODS The patients with coronary heart disease of Qi deficiency and blood stasis syndrome were treated with Yiqi Huoxue decoction for 3 months,and the changes of cardiac function were observed.61 serum samples(including 29 cases of disease group and 32 cases of Yiqi Huoxue expression group)were analyzed by non labeled proteomics.The disease group was used as the control group,and the protein with expression level difference of more than 1.2 folds(P<0.05)was screened.The molecular function,biological pathway and protein interaction of the different proteins were analyzed by bioinformatics,so as to identify the molecular and biological pathway of Yiqi Huoxue decoction in the treatment of coronary heart disease with Qi deficiency and blood stasis syndrome.RESULTS Clinical treatment found that Yiqi Huoxue decoction can improve TCM syndrome score and left ventricular ejection fraction,regulate blood glucose and blood lipid levels,prolong thrombin time,and improve heart function.The results of proteomic quantitative analysis showed that there were 69 proteins with different expression levels in the disease group.Bioinformatics analysis results showed that Yiqi Huoxue decoction may regulate ApoA1,alpha-2 and other proteins to act on HDL assembly,platelet degradation,PI3K Akt signaling pathway,and then play a therapeutic role in coronary heart disease with Qi deficiency and blood stasis syndrome.CONCLUSION Yiqi Huoxue decoction can effectively improved the heart function decline caused by Qi deficiency and blood stasis syndrome of coronary heart disease.It mainly act on energy metabolism and platelet activation pathway by activating HDL assembly and platelet degradation signal pathway proteins.This study can provide reference for the follow-up treatment mechanism of Qi deficiency and blood stasis syndrome of coronary heart disease.展开更多
Aim Reduction of Sheng-Nao-Kang decoction （RSNK）, is a modified traditional Chinese medicinal formula of Sheng-Nao-Kang pill preparation, which is protective in rats against focal cerebral ischemia/reperfusion （I/R...Aim Reduction of Sheng-Nao-Kang decoction （RSNK）, is a modified traditional Chinese medicinal formula of Sheng-Nao-Kang pill preparation, which is protective in rats against focal cerebral ischemia/reperfusion （I/R） injury. In the current study, we investigate the protective effect of RSNK against apoptosis and oxidative damage induced by cerebral I/R and explore the underlying mechanisms. Cerebral I/R injury was induced by in- traluminal middle cerebral artery occlusion （MCAO） for 2 h followed by reperfusion for 24 h in adult male Sprague- Dawley rats. Rats were randomized into seven groups （n- 8）： Sham group, I/R group, RSNK-treated groups （ 0.7 g · kg ^- 1, 1 . 4 g · kg ^- 1 and 2. 8 g · kg^ - 1 ） , nimodipine （NMP） -treated group and Whitmania pigra Whitman （WW）-treated group. Neurological deficit scores, cerebral humidity content and cerebral infarction volume were measured after the 24 h reperfusion. Malondialdehyde （ MDA）, superoxide dismutase （ SOD）, catalase （ CAT）, inducible nitric oxide synthase （iNOS） and total nitric oxide synthase （TNOS） in serum were measured by assay kits for biochemical analysis. Histological structures of the cortex of the ipsilateral ischemic cerebral hemisphere in rats were observed by Nissl staining. The caspase-3 protein content in the hippocampus and cortex was detected by immunohistochemistry. Additionally, Bax and Bcl-2 protein expressions in the injured brain were evaluated by Western blot. RSNK administration not only markedly improved neurological deficit scores, but also reduced cere- bral humidity content and cerebral infarction volume, lowered MDA content, up-regulated SOD and CAT levels, down-regulated iNOS and TNOS levels, restrained the expression of caspase-3 positive protein and alleviated the Bax and Bcl-2 protein expressions.展开更多
OBJECTIVE To evaluate the effects of Tong-Qiao-Huo-Xue decoction(TQHXD)on the bloodbrain barrier(BBB)permeability and the expressions of related proteins on the rats;and to analyse the constituents in the cerebrospina...OBJECTIVE To evaluate the effects of Tong-Qiao-Huo-Xue decoction(TQHXD)on the bloodbrain barrier(BBB)permeability and the expressions of related proteins on the rats;and to analyse the constituents in the cerebrospinal fluid on the rats with cerebral ischemic injury.METHODS Cerebral ischemia rats were induced by middle cerebral artery occlusion(MCAO).Adult male sprague-dawley(SD)rats were randomly divided into seven groups:sham-group;model group;nimodipine(NMP)-treated group and nao mai tai(NMT)-treated group were set as positive drug control groups;TQHXD-treated group(3,6 and 12g·kg-1body weight);The neurological function of rats was estimated by neurological defect scoring after the 1,7and 15 dafter administration.Histological structure of the brain in rats were observed by hematoxylin and eosin(H&E)staining.Ultramicrostructural features of hippocampus neurons and the opening of tight junction(TJ)of BBB in rats were observed by transmission electron microscope(TEM).Western blotting was performed to detect the expression of ZO-1,occludin,claudin-5,AQP-4 and MMP-9 in BBB after cerebral ischemia injury.Component analysis experiments:adult male SD rats were randomly divided into four groups:Distilled water was administered intragastrically sham-operated rats;Distilled water was administered intragastrically model rats by MCAO;TQHXD was administered intragatrically to rats in sham-operated group;TQHXD was administered intragestrically to rats in model group by MCAO.GC and HPLC was used to detect three compounds,namely,muscone,ligustilide and hydroxysafflor yellow A,in rats cerebrospinal fluid(CSF)after oral administration of TQHXD.Finally,samples of cerebrospinal fluid of rats in each group were compared with single medicine so as to explicit the three compounds come from which herb.RESULTS TQHXD significantly reduced the neurological defect scores.Histological examination indicated that dense neuropil and largely surviving neurons had been seen in TQHXD-treated rats.TEM observation revealed that TQHXD could significantly inhibit the damage of hippocampal neurons and reduce the opening of TJ.The decreased protein expression levels of claudin-5,occludin,ZO-1 and the increased protein expression levels of AQP-4 and MMP-9in cerebral ischemia tissue were significantly prevented by treatment of TQHXD.Analysis of experimental results showed that muscone,ligustilide and hydroxysafflor yellow A could penetrate the BBB into the CSF,and the content of the model group was lower than that of sham group after intragastric administration of TQHXD.CONCLUSION These results demonstrated that TQHXD may act as a potential neuroprotective agent against BBB damage for cerebral ischemia through protecting of hippocampus neurons,reducing the opening of TJ and decreasing the permeability of BBB by up-regulating ZO-1,occludin,claudin-5 expressions,down-regulating AQP-4 and MMP-9 expressions.The effect of TQHXD on the decrease of the opening of TJ also reduced the content of muscone,ligustilide and hydroxysafflor yellow A in cerebrospinal fluid.展开更多
OBJECTIVE To construct the neuroendocrine immunomodulation(NIM) sub-network regulated by Liuwei Dihuang decoction(LW) and analyze its characteristics.METHODS We took the GSE57273 in GEO database and screened the diffe...OBJECTIVE To construct the neuroendocrine immunomodulation(NIM) sub-network regulated by Liuwei Dihuang decoction(LW) and analyze its characteristics.METHODS We took the GSE57273 in GEO database and screened the differentially expressed genes(DEGs)(P<0.01) by the GEO2 R tool as gene expression signature of LW.The global PPI network was constructed in the context of whole PPI network through direct interaction algorithm and forest algorithm respectively.Then the enrichment and the topological characteristics of NIM signaling molecules were evaluated by permutation test.Finally,we abstracted the NIM sub-network by NIMNT,which combined the NIM molecular network and forest algorithm,and analyzed the topological characteristics of it by the Network Analyzer(release 2.7) plugin in Cytoscape v3.5.1.RESULTS We got 2468 DEGs in the gene expression signature of LW.After analyzing the global PPI network of LW got by two kinds of algorithms,we found that the NIM signaling molecules significantly enriched and located in important positions in the global PPI network.The NIM sub-network regulated by LW contained 1099 nodes and 1056 edges.We screened out 22 hub nodes(Degree>10).Among them,there were 19 NIM signaling molecules in which only ESR1 changed significantly and 3 non-DEGs(NFATC2,RARA,TP53).However,the down.stream of the hub nodes were significantly changes.CONCLUSION The results suggested that LW might mainly regulate the non-hub nodes to recovery of the network imbalance of the body in the state of disease.展开更多
OBJECTIVE To investigate the effect and mechanisms of Liuwei Dihuang Decoction(LW) on cognition in PrP-hAβPPswe/PS1ΔE9(APP/PS1) transgenic mice.METHODS LW was adminis.trated with oral for 3 months.The locomotor acti...OBJECTIVE To investigate the effect and mechanisms of Liuwei Dihuang Decoction(LW) on cognition in PrP-hAβPPswe/PS1ΔE9(APP/PS1) transgenic mice.METHODS LW was adminis.trated with oral for 3 months.The locomotor activity test was performed to investigate the spontaneous motor activity of mice.The Morris water maze test and shuttle box test were performed to investigate the spatial learning and memory and active avoidance response respectively.The Αβ deposits and neuron loss in the hippocampus was detected by immunofluorescence staining and nissl staining respectively.The flow cytometry was employed to investigate the lymphocyte subsets of the mice.The 3 H-thymidine incorporation was performed to investigate the splenocytes proliferation.RESULTS The treatment of LW ameliorated the impairments of spatial learning and memory and active and passive avoidance in APP/PS1 mice.The administration of LW alleviated neuron loss in the brain,suppressed amyloid-β(Αβ) deposits in the hippocampus of APP/PS1 mice.The treatment of LW significantly increased ConAand LPS-induced proliferation of splenocytes,increased CD3+ T cells and CD19+ B cells in the spleen lymphocytes and reduced Gr1+ cells in APP/PS1 mice.CONCLUSION This data indicated the adminis.tration of LW ameliorated behavioral and pathological deterioration via regulating immune function.展开更多
OBJECTIVE To explore the biomarkers and molecular mechanism of Huanglianjiedu decoction(HJD) on high fat diet-induced experimental atherosclerosis in rats.METHODS SD male rats were randomly dividedinto five groups(n=8...OBJECTIVE To explore the biomarkers and molecular mechanism of Huanglianjiedu decoction(HJD) on high fat diet-induced experimental atherosclerosis in rats.METHODS SD male rats were randomly dividedinto five groups(n=8):normal control group,model group,and three dosage groups(1.5,3 and 6 g crude drug per kilogram of body weight).Atherosclerosis was induced by the combination of regular intraperitoneal injection of vitamin D3 and high fat diet for 8 weeks.HJD was administered by oral gavage from the third week once per day and until the end of the study.After the final administration,the blood samples were collected for biochemical analyses [total cholesterol(TC),triglycerides(TG),highdensity lipoprotein(HDL-C),low-density cholesterol(LDL-C)] and blood gas analyses(PaO_2,PaCO_2,pH,ctHb,etc);the abdominal aorta sections were stained with hematoxylin and eosin for histopathology;the liver homogenate were determined for MDA,SOD,OX-LDL,MCP-1 and VCAM-1.The plasma samples were detected using ultraper formance liquid chromatography coupled with quadrupole-time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS).The data of endogenous compounds were preliminarily preprocessed by software Progenesis QI and then analyzed by multivari.ate statistical analysis software EZinfo 2.0 to screen the distinguished biomarkers and the metabolic pathways were analyzed through website http://www.metaboanalyst.ca/.RESULTS Compared with the normal control group,the content of TC,TG,LDL-C,PaCO_2,MDA,Ox-LDL,MCP-1 and VCAM-1 were significantly increased and HDL-C,PaO_2,ctHb and SOD decreased in the atherosclerosis rats.HJD could significantly attenuated the high fat-induced atherosclerosis pathological injury and the abovementioned indexes(P<0.05).The five groups could be clearly distinguished using the metabolomics method.The administration groups profile exhibited an apparent returning trend from that of the model group and that of the normal control group.Twenty-one endogenous metabolites has been significantly changed in atherosclerosis rats.HJD could remarkably up-regulate 5-L-glutamyl-taurine,L-beta-aspartylL-glutamic acid,histidinyl-hydroxyproline,tryptophyl-alanine,4′-O-methyl-(-)-epicatechin,and downregulate protoporphyrin IX,azelaic acid,lacto-N-triaose,cinnamoylglycine and 9′-carboxy-alpha-tocotri.enol.CONCLUSION The beneficial effect of HJD in high fat-induced atherosclerosis rats may be due to anti-oxidant and anti-inflammatory.And it is suggested that HJD may affect the model rats through tryptophan metabolism,taurine and hypotaurine metabolism,histidine metabolism,lysine degradation and porphyrin and chlorophyll metabolism pathway.展开更多
基金The project supported by National Natural Science Foundation of China(81473383,81573645)
文摘OBJECTIVE Xiao-xu-ming decoction(XXMD),a well-known traditional Chinese herbal prescription,has been widely used to treat stroke.It is recorded in″Bei Ji Qian Jin Yao Fang″written by Si-miao Sun of the Chinese ancient Tang Dynasty.In our previous study,the active fraction of XXMD(XXM)against cerebral ischemia has been prepared by modern separation and purification techniques.This study was to investigate XXM against lipopolysaccaride(LPS)-induced neuroinflammation in mice.METHODS LPS is an endotoxin from the outer membrane of Gram-negative bacteria that activates inflammation.XXM was pre-treated in BALB/C mice followed by injected intraperitoneally with LPS(5 mg·kg-1).The effects of XXM on LPS-induced pro-inflammatory factors and proteins were measured by ELISA,Western blot,and immunofluorescence in vivo.RESULTS Mice treated with XXM showed significantly decreased proinflammatory factors level,including IL-1β(P<0.01),IL-6(P<0.01),TNF-α(P<0.05),and MCP-1(P<0.01).Furthermore,XXM also significantly inhibited the inflammatory pathway proteins expression induced by LPS,including TLR4,MyD 88,and COX-2.CONCLUSION XXM possesses anti-neuroinflammation in mice and might be a promising therapeutic agent for stroke.
基金supported by Major Scientific and Technological Project of China(2013ZX095081042013ZX09402203)+1 种基金 CAMS Innovation Fund for Medical Sciences(2016-I2M-3-007) Central Public Scientific Re.search Institution Fundamental Project(2014CX05)
文摘OBJECTIVE Using bioinformatics methods,to establish Xiao-Xu-Ming decoction(XX.MD) "compound-vasoconstriction G Protein-Coupled Receptors(GPCR) targets" network,and analyze the vasoconstriction regulatory effective components and the potential targets of XXMD.METHODS Ac.cording to the XXMD herb sources,we retrieved the chemical structures from the national scientific da.ta sharing platform for population and health pharmaceutical information center,TCMSP database and the latest research literature.The chemical molecular library was established after class prediction and screening for medicinal and metabolic properties.Five kinds of vasoconstriction GPCR crystal structure including 5-HT receptors(5-HT1 AR,5-HT1 BR),AT1 R,β2-AR,hUTR and ETB were retrieved from Bank Pro.tein Data Bank database or homology modeling using Discovery Studio 4.1 built-in modeling tools.After virtual screening by Libdock molecular docking,the highest rated 50 compounds of each target were col.lected and analyzed.The collected data were further used to construct and analyze the network.RE.SULTS 859 single compound structures information in XXMD were generalized following the screen.ing of obtained 2043 compounds.The complicated compound-vasoconstriction GPCR targets network of XXMD was then constructed and analyzed by molecular docking with the above five kinds of GPCR target receptors.Most of the chemical composition effects were associated with different vasoconstric.tion GPCR targets,while a few effective components can be applied to multiple GPCR targets at the same time,therefore forming synergies.CONCLUSION Vasorelaxant effects of XXMD may not only result from the collaborative interaction between a variety of active ingredients in Chinese medicine and multi.ple targets,but also from the interaction between some effective component and multiple targets.
基金supported by National Natural Science Foundation of China(81473383) National Science and Technology Major Project of China(2018ZX09711001-003-019)+1 种基金 CAMS Innovation Fund for Medical Sciences(2016-I2M-3-007) Innovation Fund for Graduate of Beijing Union M
文摘OBJECTIVE Vascular dementia(VD) refers to a progressive decline in memory and cognitive function caused by chronic cerebral ischemia.2-Vessels occlusion(2-VO) has been widely used as a model of VD.Xiao-Xu-Ming decoction,a well-known traditional Chinese medicine prescrip.tion,has been widely used to treat stroke and sequelae of stroke.The present study was to investigate the mechanism of Xiao-Xu-Ming decoction(XXM) against chronic cerebral ischemia injury in rats.METHODS After XXM treatment,rats were performed a memory testing with Morris water maze and motor ability testing using prehensile test and inclined screen test.Neuronal plasticity was observed by immunofluorescent staining with MAP2 antibody.Differentially expressed proteins of rat hippocampus were analyzed by Label-free quantitative proteomics.RESULTS XXM significantly alleviated 2-VOinduced learning and memory deficits,motor ability dysfunction,and neuronal plasticity injury in rats.The mechanism might be involved in up-regulation of 39 proteins and down-regulation of 13 proteins in the hippocampus of rats after XXM treatment vs 2-VO group rats.Gene ontology and pathway analysis showed that the regulated proteins are mainly involved in oxidation reduction process,intracellular signaling cascade process,and protein catabolic process,etc.The signal pathways are mainly involved in ubiquitin mediated proteolysis and phosphatidylinositol signaling system.CONCLUSION Current findings provide new insights into the molecular mechanisms of XXM on chronic cerebral ischemia.
基金The project supported by Major Scientific and Technological Special Project for "Significant New Drug Creation"(2013ZX09508104,2013ZX09402203)by Central Public Scientific Research Institution Fundamental Project(2014CX05)
文摘OBJECTIVE To investigate the cerebralvasorelaxant material basis of Xiaoxuming decoction.METHODS According to the Xiaoxuming decoction herb sources,we retrieved the chemical structure from the literatures and the Chinese Natural Product Database(http://pharmdata.ncmi.cn).By using microvessel tension system,we checked the vasorelaxanteffects of Xiaoxuming decoction anti-cerebral ischemia effective components group(XXMDECG)and the available composition compounds on pre-contracted basilar artery ring.RESULTS963 compoundsin the decoction,including 81Fangfeng,77 Mahuang,130 Shengjiang,31 Guizhi,91 Huangqin,127 Renshen,73 Chuanxiong,44 Shaoyao,39 Xingren,42 Fangji,62 Fuzi and 166 Gancao were collected.The five largest number classes of compounds in the decoction are volatile oil(32%),flavone(32%),alkaloid(13%),saponin(7%),polyphenol and organic acid(5%).XXMDECG at concentration from 1 to 400μg·mL-1can dilate the KCl(60 mmol·L-1)and ET-1(0.01μmol·L-1)pre-contracted rat basilar artery rings in a dose-dependent manner.There are 6 compounds with vasorelaxant ratio more than 50%at the concentration of 10μmol·L-1.CONCLUSION Xiaoxuming decoction contains abundant chemical structure.It has the material basis of multiple ingredients and multiple targets.The XXMDECG are able to dilate the rat basilar artery rings in a dose-dependent manner.The network interactions between varies of chemical compounds in Xiaoxuming decoction and the vasoconstriction associated targets result in the comprehensive regulation mechanisms of vascular function.
文摘OBJECTIVE Cranial radiotherapy is clinically used in the treatment of brain tumors;however,the consequent cognitive and emotional dysfunctions seriously impair the life quality of patients.LW-AFC,an active fraction combination extracted from classical traditional Chinese medicine prescription Liuwei Dihuang decoction,can improve cognitive and emotional dysfunctions in many animal models;however,the protective effect of LW-AFC on cranial irradiation-induced cognitive and emotional dysfunctions has not been reported.Recent studies indicate that impairment of adult hippocampal neurogenesis(AHN)and alterations of the neurogenic microenvironment in the hippocampus constitute critical factors in cognitive and emotional dysfunctions following cranial irradiation.Here,our research further investigated the potential protective effects and mechanisms of LW-AFC on cranial irradiation-induced cognitive and emotional dysfunctions in mice.METHODS LW-AFC(1.6 g·kg^(-1))was intragastrically administered to mice for 14 d before cranial irradiation(7 Gyγ-ray).AHN was examined by quantifying the number of proliferative neural stem cells and immature neurons in the dorsal and ventral hippocampus.The contextual fear conditioning test,open field test,and tail suspension test were used to assess cognitive and emotional functions in mice.To detect the change of the neurogenic microenvironment,colorimetry and multiplex bead analysis were performed to measure the level of oxidative stress,neurotrophic and growth factors,and inflammation in the hippocampus.RESULTS LW-AFC exerted beneficial effects on the contextual fear memory,anxiety behavior,and depression behavior in irradiated mice.Moreover,LW-AFC increased the number of proliferative neural stem cells and immature neurons in the dorsal hippocampus,displaying a regional specificity of neurogenic response.For the neurogenic microenvironment,LW-AFC significantly increased the contents of superoxide dismutase,glutathione peroxidase,glutathione,and catalase and decreased the content of malondialdehyde in the hippocampus of irradiated mice,accompanied by the increase in brain-derived neurotrophic factor,insulin-like growth factor-1,and interleukin-4 content.Together,LW-AFC improved cognitive and emotional dysfunctions,promoted AHN preferentially in the dorsal hippocampus,and ameliorated disturbance in the neurogenic microenvironment in irradiated mice.CONCLUSION LW-AFC ameliorates cranial irradiation-induced cognitive and emotional dysfunctions,and the underlying mechanisms are mediated by promoting AHN in the dorsal hippocampus and improving the neurogenic microenvironment.LW-AFC might be a promising therapeutic agent to treat cognitive and emotional dysfunctions in patients receiving cranial radiotherapy.
基金The project supported by the Key Program of Natural Science Foundation of China(90709012)National Natural Science Foundation of China(30701073)
文摘OBJECTIVE To investigate age-related functional change of hypothalamus-pituitary-adrenal(HPA)axis in senescence accelerated mouse(SAM)and the effects of Liuwei Dihuang decoction(LW)and its San-bu(three tonics)and San-xie(three eliminators)components on the function of HPA axis.METHODS Male SAM-resistance/1(SAMR1)and SAM-prone/8(SAMP8)at the ages of 6and 12 months old were used.SAMP8 were orally administered with LW,three tonics and three eliminators at the doses of 10,6.4and 3.6g·kg-1·d-1,respectively,for consecutive 60 d.Serum level of CORT was assayed with ELISA method.The levels of hypothalamic CRH and pituitary ACTH was determined with radioimmunoassay.RESULTS The levels of hypothalamic CRH,pituitary ACTH and serous CORT were much higher in 6 and 12 months old SAMP8 than those in age-matched SAMR1,which suggested the abnormal function of HPA axis in SAMP8.Oral administration of LW and three tonics significantly decreased the level of hypothalamic CRH of 6 and 12 months old SAMP8,and reduced the levels of pituitary ACTH and serous CORT of 6 month old SAMP8.Three eliminators significantly decreased the level of hypothalamic CRH of 6 months old SAMP8.The results indicated that oral administration of LW,three tonics and three eliminators improved the function of HPA axis of SAMP8.CONCLUSION The results showed the hyperactivity of HPA axis of SAMP8,and LW improved the hyperactivity of 6 month old SAMP8.Three tonics and three eliminators had similar effects as LW,which had better effect after compatibility.
文摘OBJECTIVE To screen the active ingredients preventing platelet aggregations from Taohong Siwu Decoction. METHODS Fresh blood from healthy adult volunteer was collected with vacuum tube for preparation of platelet suspension. Platelet suspension was incubated with Taohong Siwu Decoction for one hour at 37℃,then centrifuged. The precipitate was washed and desorbed with buffer solutions.The differences of chemical constituents between incubated and unincubated were identified with high performance liquid chromatography-diode array detector. RESULTS According to the chromatograph at 254 nm,at least three kinds of different components were detected in Taohong siwu decoction before and after incubated with platelet. CONCLUSION Platelet suspension can be used for screening active ingredients on platelet membrane receptor from the traditional Chinese medicine.
基金supported by National Science and Technology Major Project(2013ZX09508104,2012ZX09301003-002-001)
文摘OBJECTIVE To investigate the effects of LW-AFC,a new formula derived fromLiuwei Dihuang decoction,on gut microbiota and the behavior of learning and memory of SAMP8 mice,a mouse model of Alzheimer Disease(AD),and identify the specific intestinal microbiota correlating with cognitive ability.METHODS Morris-water maze test,novel object recognition test and shuttle-box test were conducted to observe the ability of learning and memory.16S rRNA amplicon sequencing(Illumina,San Diego,CA,USA)was employed to investigate gut microbiota.RESULTS The treatment of LW-AFC improved cognitive impairments of SAMP8 mice,including spatial learning and memory ability,active avoidance response,and object recognition memory capability.Our data indicated that there were significantly 8 increased and 12 decreased operational taxonomic units(OTUs)in the gut microbiota of SAMP8 mice compared with senescence accelerated mouse resistant 1(SAMR1) strains,the control of SAMP8 mice.The treatment of LW-AFC altered 22(16 increased and 6 decreased)OTUs in SAMP8 mice and among them,15 OTUs could be reversed by LW-AFC treatment resulting in a microbial composition similar to that of SAMR1 mice.We further showed that there were7(3 negative and 4 positive correlation)OTUs significantly correlated with all the three types of cognitive abilities,at the order level,including Bacteroidales,Clostridiales,Desulfovibrionales,CW040,and two unclassified orders.LW-AFC had influences on bacterial taxa correlated with the abilities of learning and memory in SAMP8 mice and restored them to SAMR1 mice.CONCLUSION The effects of LW-AFC on improving cognitive impairments of SAMP8 mice might be via modulating intestinal microbiome and LW-AFC could be used as a potential anti-AD agent.
基金National Natural Science Foundation of China(82174143)and Scientific Research Foundation of Guangdong Pharmaceutical University(51348136)。
文摘OBJECTIVE Cisplatin is a formidable chemotherapy agent widely applying in antineoplastic treatments,but its side effects often limit the clinical usage.Metabolic disorders are one of the side effects induced by cisplatin,which closely relate to the onset of chemotherapy-induced anorexia(CIA)in cancer patients but lacks effective controls.Liujunzi decoction(LJZD)is a traditional Chinese formula that has a promising effect in treating CIA.However,whether LJZD ameliorates CIA through adjusting cisplatin-induced metabolic disorders remain unknow.The present study evaluated the mechanism of cisplatin-induced metabolic disorders,and the effect of LJZD in ameliorating these disturbances.METHODS 42 male Sprague-Dawley(SD)rats(180-220 g)were randomly divided into 3 groups:normal control group(distilled water+saline),model group(distilled water+cisplatin),LJZD group(4.8 g·kg^(-1)Liujunzi decoction ingredients+cisplatin).Intragastrical administered each drug twice a day(7∶00-19∶00)since day 0 for 4 d,animals were intraperitoneal injected with cisplatin 6 mg·kg^(-1)1 h after administration while normal control groups were injected with same volume of saline.On day 3,each group was anesthetized with pentobarbital sodium 45 mg·kg^(-1)(ip),and blood samples were collected from aorta abdominalis.Then the samples were analyzed using an LC-ESI-MS/MS system.Significantly regulated metabolites between groups were determined by VIP≥1 and absolute Log2FC(fold change)≥1.Identified metabolites were mapped to Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway database using Metaboanalyst 5.0(https://www.metaboanalyst.ca/).RESULTS A total of 133,77 and 32 differential metabolites were filtrated in control vs model,control vs LJZD and model vs LJZD groups respectively.Comparing to control,the levels of hexadecanoic acid(Log2FC=6.3153),linoleic acid(Log2FC=5.3478),and 8,11-icosadienoic acid(Log2FC=5.2342)significantly increased,and the levels of N-acetyl-L-tyrosine(Log2FC=-2.6283),cinnamic acid(Log2FC=-2.3381),N-acetylphenylalanine(Log2FC=-2.2501)significantly decreased in model group.The KEGG pathway enrichments of these metabolites indicated that,cisplatin-induced metabolic disorders by disturbing metabolism pathways such as linoleic acid metabolism,biosynthesis of unsaturated fatty acids,and phenylalanine metabolism,which suggested that the onset of CIA was partly associated with the metabolic disorders of linoleic acid,unsaturated fatty acids,and phenylalanine.Compared to control,treatment of LJZD significantly increased the levels of 4-hydroxytryptamine(Log2FC=12.0186),hexadecanoic acid(Log2FC=5.7412),linoleic acid(Log2FC=5.1877)and significantly decreased the levels of N-acetylmethionine(Log2FC=-1.7317),2-aminoethanesulfinic acid(Log2FC=-1.6578),N-acetyl-L-tyrosine(Log2FC=-1.5355).And comparing to the model group,4-hydroxytryptamine(Log2FC=12.0186),7,12-diketocholic acid(Log2FC=2.0998),N-acetylneuraminic acid(Log2FC=2.0560)markedly increased,and 3-hydroxy-3-methylpentane-1(Log2FC=-1.9202),5-dioic acid(Log2FC=-1.7166),N-isovaleroylglycine,hexanoyl glycine(Log2FC=-1.4958)markedly decreased in LJZD group.It was worth noting that,there were 23 differential metabolites filtrated both in control vs model and model vs LJZD groups,which were the key metabolites of LJZD in treating CIA.Among these 23 common metabolites,there were 16 metabolites excluding the control vs LJZD group,that was,LJZD had no effect in normal rats while being able to ameliorated cisplatin-induced metabolic disorders by regulating these 16 metabolites.Cisplatin-induced downregulation of 11 metabolites such as hydrocinnamic acid,(±)12(13)epoxy-9Z-octadecenoic acid,cinnamic acid were upregulated after LJZD treatment,and cisplatin-induced upregulation of imidazoleacetic acid,2′-deoxycytidine-5′-monophosphate and other 5 metabolites were downregulated by LJZD.The KEGG pathway analysis indicated that the linoleic acid metabolism,histidine metabolism,and pyrimidine metabolism were the most enriched metabolic pathway.Thus,cisplatin-induced metabolic disturbances mainly by disturbing linoleic acid metabolism,histidine metabolism,and pyrimidine metabolism,and LJZD interacted with these metabolic pathways to reduce metabolic disorders and thus ameliorated CIA.CONCLUSION Cisplatin-induced anorexia was closely related to the metabolic disorders of linoleic acid metabolism,biosynthesis of unsaturated fatty acids,and phenylalanine metabolism.The mechanism of LJZD in ameliorating CIA was in concerned with the metabolic adjustments,relating to the regulation of linoleic acid metabolism,histidine metabolism,and pyrimidine metabolism.
基金National Natural Science Foundation of china(8216140711)Natural Science Foundation of Guangxi Province(2017GXNSFAA198255)+2 种基金Natural Science Foun⁃dation of Guangxi Province(2018GXNSFBA138028)Open Project Program of Guangxi Key Laboratory of Brain and Cognitive Neuroscience,GuilinMedicalUniversity(GKLBCN-20180105-03)and 2019 College Student Innovation and Entre⁃preneurship Project Training Program(201910601038)。
文摘OBJECTIVE To investigate the effects of Huanglian Jiedu decoction on cognitive dysfunction of zebrafish with Alzheimer disease.METHODS 126 g of coptis chinensis,84 g of phellorescent phellorescent chinensis,84 g of scutellaria chinensis and 126 g of gardenia chinensis were immersed in 10,8 and 8 times of water for 30 min,and then extracted at 100℃for 2,1.5 and 1.5 h,respectively.The three extracts were coarse filtered and concentrated into 308 g·L-1 and stored in refrigerator for later use.200 zebrafish were selected for behavioral train⁃ing in T-shaped tank for seven days.After that,the behavioral record analysis software Smart 3.0 was used to conduct behavioral analysis.Qualified zebrafish were selected as the blank group.Except for the blank group,zebrafish in the other 5 groups were exposed to AlCl3100μg·L-1 aquaculture water for modeling,and exposed for 6 d.The behavioral record analysis software Smart 3.0 was used to conduct behavioral analysis,and Select the successfully modeled zebraf⁃ish.After that,huperzine A(4μg·L-1)and Huan⁃glian Jiedu decoction of low,medium and high doses(154,308 and 616 mg·L-1)were adminis⁃tered respectively,and exposed for six days.Then,the behavior analysis was conducted again through the behavioral record analysis soft⁃ware Smart 3.0 to select qualified zebrafish.After the training,the brain and gut of zebrafish in each group were collected,and the expression changes of N-cadherin,p-P38/p38MAPK and p-Tau in the brain were detected by Western blot⁃ting and qPCR to show the effect of Huanglian Jiedu decoction on cognitive dysfunction of Zebrafish with Alzheimer disease.RESULTS Western blotting and qPCR results showed that the contents of N-cadherin increased(P<0.05),and the contents of p-P38/p38MAPK and p-Tau decreased(P<0.05)compared with the model group,indicating that Huanglian Jiadu decoction had an effect on the cognitive dysfunction of zebrafish with Alzheimer disease.CONCLU⁃SION Huanglian Jiedu decoction can alleviate cognitive dysfunction of zebrafish model with Alzheimer disease to a certain extent.
文摘Aim This work is to provide a network approach to identify the potential therapeutic targets in molecular level for xuefu-zhuyu decoction （XZD） and gualou-xiebai-banxia decoction （GXBD） in treating Coronary artery dis- ease （CAD）. Methods The networks between the ingredients/drugs and relevant target proteins for XZD, GXBD, and modern anti-CAD drugs were constructed, respectively. A master network based on the three established networks was further generated. By comparing the similarities and the differences of the targets containing in the master net- work between the individual formula and the modern drugs, the potential anti-CAD targets for XZD and GXBD were i- dentified for further pharmacological investigations. Results Although the herbal formulations and the chemical con- stituents of XZD and GXBD were significant different, both formulas presented the great similarity on target proteins and with the Tanimoto coefficient of 0. 7225. Comparison the formula-specific targets to modem drugs targets, 50 mu- tual targets with higher possibility were modulated. Moreover, a total amount of 114 mutual targets between formulas derived from the master network were identified to be not yet related to those of the approved anti-CAD drugs. Among them, the top 10 targets were identified to be NOS3, PTPN1, GABRA1, PRKACA, CDK2, MAOB, ESR1, ADH1C, ADH1B and AKR1B1. The formula-specific targets of XZD or GXBD which were not yet covered by the current anti- CAD drugs provided the potential opportunities to discovery of the new drug candidates from the two formulas for CAD treatment. Conclusion The established method of network analysis provides a novel approach for screening of the potential therapeutic targets based on the chemical constituents in traditional Chinese medicines or formulas. It is cru- cial for this work to select relatively favorable therapeutic areas of traditional Chinese medicines, syndrome-oriented formulas and syndrome differentiation of same diseases. Meanwhile, this kind of work is helpful for unveiling the mo- lecular mechanism of TCM formulas.
基金Project (02jjy3034) supported by the Nature Science Foundation of Hunan Province
文摘Objective Study on the effect of NF-κB in ox-LDL injured HUVEC-304 and the intervention with the serum of Tongmai Decoction. Methods Tongmai Decoction herbage-contained serum was made by the serum pharmacology methods, then the HUVEC-304 cells were divided into 5 groups and incubated for 24 h: 1) normal group;2) fetal calf serum group; 3) ox-LDL group; 4) simvastatin group; 5) Tongmai Decoction group. RT-PCR was used to determine the mRNA of NF-κB in the cells, Western Blot Assay was used to determine the protein content of NF-κB in the cells. Results 1) Compared with the cells in normal group and serum control group , the endothelial cells in ox-LDL group are seriously injured, while those in Tongmai Decoction group grow better; 2) Compared with the cells in normal group and fetal calf serum group, the expressions of NF-κB gene and protein are up-regulated in ox-LDL group(P＜0.05, P＜0.01); 3) Compared with the cells in ox-LDL group, the expression of NF-κB gene and protein in Tongmai Decoction group are significantly down-regulated, there is no difference between Tongmai Decoction group and simvastatin group(P＞0.05). Conclusion Tongmai Decoction can protect the injured endothelial cells, up-regulate the expressions of NF-κB gene and protein content.
基金National Natural Science Foundation of China(82030124)and National Key Basic Research Special Foundation of China(2015CB554400)。
文摘OBJECTIVE To explore the curative effect and mechanism of Yiqi Huoxue decoction in the treatment of coronary heart disease with Qi deficiency and blood stasis syndrome.METHODS The patients with coronary heart disease of Qi deficiency and blood stasis syndrome were treated with Yiqi Huoxue decoction for 3 months,and the changes of cardiac function were observed.61 serum samples(including 29 cases of disease group and 32 cases of Yiqi Huoxue expression group)were analyzed by non labeled proteomics.The disease group was used as the control group,and the protein with expression level difference of more than 1.2 folds(P<0.05)was screened.The molecular function,biological pathway and protein interaction of the different proteins were analyzed by bioinformatics,so as to identify the molecular and biological pathway of Yiqi Huoxue decoction in the treatment of coronary heart disease with Qi deficiency and blood stasis syndrome.RESULTS Clinical treatment found that Yiqi Huoxue decoction can improve TCM syndrome score and left ventricular ejection fraction,regulate blood glucose and blood lipid levels,prolong thrombin time,and improve heart function.The results of proteomic quantitative analysis showed that there were 69 proteins with different expression levels in the disease group.Bioinformatics analysis results showed that Yiqi Huoxue decoction may regulate ApoA1,alpha-2 and other proteins to act on HDL assembly,platelet degradation,PI3K Akt signaling pathway,and then play a therapeutic role in coronary heart disease with Qi deficiency and blood stasis syndrome.CONCLUSION Yiqi Huoxue decoction can effectively improved the heart function decline caused by Qi deficiency and blood stasis syndrome of coronary heart disease.It mainly act on energy metabolism and platelet activation pathway by activating HDL assembly and platelet degradation signal pathway proteins.This study can provide reference for the follow-up treatment mechanism of Qi deficiency and blood stasis syndrome of coronary heart disease.
文摘Aim Reduction of Sheng-Nao-Kang decoction （RSNK）, is a modified traditional Chinese medicinal formula of Sheng-Nao-Kang pill preparation, which is protective in rats against focal cerebral ischemia/reperfusion （I/R） injury. In the current study, we investigate the protective effect of RSNK against apoptosis and oxidative damage induced by cerebral I/R and explore the underlying mechanisms. Cerebral I/R injury was induced by in- traluminal middle cerebral artery occlusion （MCAO） for 2 h followed by reperfusion for 24 h in adult male Sprague- Dawley rats. Rats were randomized into seven groups （n- 8）： Sham group, I/R group, RSNK-treated groups （ 0.7 g · kg ^- 1, 1 . 4 g · kg ^- 1 and 2. 8 g · kg^ - 1 ） , nimodipine （NMP） -treated group and Whitmania pigra Whitman （WW）-treated group. Neurological deficit scores, cerebral humidity content and cerebral infarction volume were measured after the 24 h reperfusion. Malondialdehyde （ MDA）, superoxide dismutase （ SOD）, catalase （ CAT）, inducible nitric oxide synthase （iNOS） and total nitric oxide synthase （TNOS） in serum were measured by assay kits for biochemical analysis. Histological structures of the cortex of the ipsilateral ischemic cerebral hemisphere in rats were observed by Nissl staining. The caspase-3 protein content in the hippocampus and cortex was detected by immunohistochemistry. Additionally, Bax and Bcl-2 protein expressions in the injured brain were evaluated by Western blot. RSNK administration not only markedly improved neurological deficit scores, but also reduced cere- bral humidity content and cerebral infarction volume, lowered MDA content, up-regulated SOD and CAT levels, down-regulated iNOS and TNOS levels, restrained the expression of caspase-3 positive protein and alleviated the Bax and Bcl-2 protein expressions.
基金The project supported by National Natural Science Foundation of China(81374005)″Twelfth Five Year″National Science and Technology Support Program(2012BAI26B03)
文摘OBJECTIVE To evaluate the effects of Tong-Qiao-Huo-Xue decoction(TQHXD)on the bloodbrain barrier(BBB)permeability and the expressions of related proteins on the rats;and to analyse the constituents in the cerebrospinal fluid on the rats with cerebral ischemic injury.METHODS Cerebral ischemia rats were induced by middle cerebral artery occlusion(MCAO).Adult male sprague-dawley(SD)rats were randomly divided into seven groups:sham-group;model group;nimodipine(NMP)-treated group and nao mai tai(NMT)-treated group were set as positive drug control groups;TQHXD-treated group(3,6 and 12g·kg-1body weight);The neurological function of rats was estimated by neurological defect scoring after the 1,7and 15 dafter administration.Histological structure of the brain in rats were observed by hematoxylin and eosin(H&E)staining.Ultramicrostructural features of hippocampus neurons and the opening of tight junction(TJ)of BBB in rats were observed by transmission electron microscope(TEM).Western blotting was performed to detect the expression of ZO-1,occludin,claudin-5,AQP-4 and MMP-9 in BBB after cerebral ischemia injury.Component analysis experiments:adult male SD rats were randomly divided into four groups:Distilled water was administered intragastrically sham-operated rats;Distilled water was administered intragastrically model rats by MCAO;TQHXD was administered intragatrically to rats in sham-operated group;TQHXD was administered intragestrically to rats in model group by MCAO.GC and HPLC was used to detect three compounds,namely,muscone,ligustilide and hydroxysafflor yellow A,in rats cerebrospinal fluid(CSF)after oral administration of TQHXD.Finally,samples of cerebrospinal fluid of rats in each group were compared with single medicine so as to explicit the three compounds come from which herb.RESULTS TQHXD significantly reduced the neurological defect scores.Histological examination indicated that dense neuropil and largely surviving neurons had been seen in TQHXD-treated rats.TEM observation revealed that TQHXD could significantly inhibit the damage of hippocampal neurons and reduce the opening of TJ.The decreased protein expression levels of claudin-5,occludin,ZO-1 and the increased protein expression levels of AQP-4 and MMP-9in cerebral ischemia tissue were significantly prevented by treatment of TQHXD.Analysis of experimental results showed that muscone,ligustilide and hydroxysafflor yellow A could penetrate the BBB into the CSF,and the content of the model group was lower than that of sham group after intragastric administration of TQHXD.CONCLUSION These results demonstrated that TQHXD may act as a potential neuroprotective agent against BBB damage for cerebral ischemia through protecting of hippocampus neurons,reducing the opening of TJ and decreasing the permeability of BBB by up-regulating ZO-1,occludin,claudin-5 expressions,down-regulating AQP-4 and MMP-9 expressions.The effect of TQHXD on the decrease of the opening of TJ also reduced the content of muscone,ligustilide and hydroxysafflor yellow A in cerebrospinal fluid.
基金supported by National Natural Science Foundation of China(81473191) and the National key Research and Development Program(2016YFC1306300)
文摘OBJECTIVE To construct the neuroendocrine immunomodulation(NIM) sub-network regulated by Liuwei Dihuang decoction(LW) and analyze its characteristics.METHODS We took the GSE57273 in GEO database and screened the differentially expressed genes(DEGs)(P<0.01) by the GEO2 R tool as gene expression signature of LW.The global PPI network was constructed in the context of whole PPI network through direct interaction algorithm and forest algorithm respectively.Then the enrichment and the topological characteristics of NIM signaling molecules were evaluated by permutation test.Finally,we abstracted the NIM sub-network by NIMNT,which combined the NIM molecular network and forest algorithm,and analyzed the topological characteristics of it by the Network Analyzer(release 2.7) plugin in Cytoscape v3.5.1.RESULTS We got 2468 DEGs in the gene expression signature of LW.After analyzing the global PPI network of LW got by two kinds of algorithms,we found that the NIM signaling molecules significantly enriched and located in important positions in the global PPI network.The NIM sub-network regulated by LW contained 1099 nodes and 1056 edges.We screened out 22 hub nodes(Degree>10).Among them,there were 19 NIM signaling molecules in which only ESR1 changed significantly and 3 non-DEGs(NFATC2,RARA,TP53).However,the down.stream of the hub nodes were significantly changes.CONCLUSION The results suggested that LW might mainly regulate the non-hub nodes to recovery of the network imbalance of the body in the state of disease.
基金supported by Chinese National Technology Major Project of New Drug Development (2012ZX09301003-002-001 2013ZX09508104)
文摘OBJECTIVE To investigate the effect and mechanisms of Liuwei Dihuang Decoction(LW) on cognition in PrP-hAβPPswe/PS1ΔE9(APP/PS1) transgenic mice.METHODS LW was adminis.trated with oral for 3 months.The locomotor activity test was performed to investigate the spontaneous motor activity of mice.The Morris water maze test and shuttle box test were performed to investigate the spatial learning and memory and active avoidance response respectively.The Αβ deposits and neuron loss in the hippocampus was detected by immunofluorescence staining and nissl staining respectively.The flow cytometry was employed to investigate the lymphocyte subsets of the mice.The 3 H-thymidine incorporation was performed to investigate the splenocytes proliferation.RESULTS The treatment of LW ameliorated the impairments of spatial learning and memory and active and passive avoidance in APP/PS1 mice.The administration of LW alleviated neuron loss in the brain,suppressed amyloid-β(Αβ) deposits in the hippocampus of APP/PS1 mice.The treatment of LW significantly increased ConAand LPS-induced proliferation of splenocytes,increased CD3+ T cells and CD19+ B cells in the spleen lymphocytes and reduced Gr1+ cells in APP/PS1 mice.CONCLUSION This data indicated the adminis.tration of LW ameliorated behavioral and pathological deterioration via regulating immune function.
基金supported by National Natural Science Foundation of China(8170382381560744) Science and Technology Research Project of Jiangxi Provincial Education Department(GJJ170753)
文摘OBJECTIVE To explore the biomarkers and molecular mechanism of Huanglianjiedu decoction(HJD) on high fat diet-induced experimental atherosclerosis in rats.METHODS SD male rats were randomly dividedinto five groups(n=8):normal control group,model group,and three dosage groups(1.5,3 and 6 g crude drug per kilogram of body weight).Atherosclerosis was induced by the combination of regular intraperitoneal injection of vitamin D3 and high fat diet for 8 weeks.HJD was administered by oral gavage from the third week once per day and until the end of the study.After the final administration,the blood samples were collected for biochemical analyses [total cholesterol(TC),triglycerides(TG),highdensity lipoprotein(HDL-C),low-density cholesterol(LDL-C)] and blood gas analyses(PaO_2,PaCO_2,pH,ctHb,etc);the abdominal aorta sections were stained with hematoxylin and eosin for histopathology;the liver homogenate were determined for MDA,SOD,OX-LDL,MCP-1 and VCAM-1.The plasma samples were detected using ultraper formance liquid chromatography coupled with quadrupole-time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS).The data of endogenous compounds were preliminarily preprocessed by software Progenesis QI and then analyzed by multivari.ate statistical analysis software EZinfo 2.0 to screen the distinguished biomarkers and the metabolic pathways were analyzed through website http://www.metaboanalyst.ca/.RESULTS Compared with the normal control group,the content of TC,TG,LDL-C,PaCO_2,MDA,Ox-LDL,MCP-1 and VCAM-1 were significantly increased and HDL-C,PaO_2,ctHb and SOD decreased in the atherosclerosis rats.HJD could significantly attenuated the high fat-induced atherosclerosis pathological injury and the abovementioned indexes(P<0.05).The five groups could be clearly distinguished using the metabolomics method.The administration groups profile exhibited an apparent returning trend from that of the model group and that of the normal control group.Twenty-one endogenous metabolites has been significantly changed in atherosclerosis rats.HJD could remarkably up-regulate 5-L-glutamyl-taurine,L-beta-aspartylL-glutamic acid,histidinyl-hydroxyproline,tryptophyl-alanine,4′-O-methyl-(-)-epicatechin,and downregulate protoporphyrin IX,azelaic acid,lacto-N-triaose,cinnamoylglycine and 9′-carboxy-alpha-tocotri.enol.CONCLUSION The beneficial effect of HJD in high fat-induced atherosclerosis rats may be due to anti-oxidant and anti-inflammatory.And it is suggested that HJD may affect the model rats through tryptophan metabolism,taurine and hypotaurine metabolism,histidine metabolism,lysine degradation and porphyrin and chlorophyll metabolism pathway.
