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
Xiao-Xu-Ming decoction has been widely used to treat stroke and sequelae of stroke. We have previously shown that the active fractions of Xiao-Xu-Ming decoction attenuate cerebral ischemic injury. However, the global ...Xiao-Xu-Ming decoction has been widely used to treat stroke and sequelae of stroke. We have previously shown that the active fractions of Xiao-Xu-Ming decoction attenuate cerebral ischemic injury. However, the global protein profile and signaling conduction pathways regulated by Xiao-Xu-Ming decoction are still unclear. This study established a two-vessel occlusion rat model by bilateral common carotid artery occlusion. Rats were intragastrically administered 50 or 150 mg/kg Xiao-Xu-Ming decoction for 4 consecutive weeks. Learning and memory abilities were measured with Morris water maze. Motor ability was detected with prehensile test. Coordination ability was examined using the inclined screen test. Neuronal plasticity was observed by immunofluorescent staining. Differentially expressed proteins of rat hippocampus were analyzed by label-free quantitative proteomics. Real time-polymerase chain reaction and western blot assay were used to identify the changes in proteins. Results showed that Xiao-Xu-Ming decoction dramatically alleviated learning and memory deficits, and motor and coordination dysfunction, and increased the expression of microtubule-associated protein 2. Xiao-Xu-Ming decoction extract remarkably decreased 13 upregulated proteins and increased 39 downregulated proteins. The regulated proteins were mainly involved in oxidation reduction process, intracellular signaling cascade process, and protein catabolic process. The signaling pathways were mainly involved in ubiquitin mediated proteolysis and the phosphatidylinositol signaling system. Furthermore, there was an interaction among Rab2 a, Ptpn1, Ppm1 e, Cdk18, Gorasp2, Eps15, Capza2, Syngap1 and Mt-nd1. Protein analyses confirmed the changes in expression of MTND1. The current findings provide new insights into the molecular mechanisms of Xiao-Xu-Ming decoction extract's effects on chronic cerebral hypoperfusion.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
In the present study, we aimed to investigate the effects of Xiao-Xu-Ming decoction extract(XXM) on lipopolysaccaride(LPS)-induced neuroinflammation in vitro and in vivo. In vitro, the microglia BV2 cells were treated...In the present study, we aimed to investigate the effects of Xiao-Xu-Ming decoction extract(XXM) on lipopolysaccaride(LPS)-induced neuroinflammation in vitro and in vivo. In vitro, the microglia BV2 cells were treated with 200 ng/mL LPS for 24 h to induce inflammatory responses. In vivo, mice were treated with 5 mg/kg LPS to induce inflammatory responses. The NO level was determined by Griess Reagents. The levels of IL-1β, IL-6, TNF-α and MCP-1 were determined by ELISA. The expressions of Iba-1, TLR4 and MyD88 at the protein levels were determined by Western blotting analysis. The mRNA levels of TLR4 and MyD88 were determined by real-time PCR. In vitro, XXM significantly reduced the levels of various pro-inflammatory factors, including NO, IL-1β, IL-6 and TNF-α, induced by LPS in the supernatant of BV2 cells and suppressed expressions of inflammatory proteins TLR4 and MyD88 induced by LPS in BV2 cells. In vivo, XXM significantly inhibited microglia activation, attenuated LPS-induced inflammatory factors and chemokine production, such as IL-1β, IL-6, TNF-α and MCP-1, and inhibited the expressions of inflammatory proteins including TLR4 and MyD88, in the cortex of LPS-induced mice. Our findings suggested that XXM could attenuate LPS-induced neuroinflammation via down-regulating TLR4/MyD88 signaling pathway.展开更多
Xiao-xu-ming decoction(XXMD)is a traditional Chinese medicine that has been widely used to treat theoplegia and its sequelae.This paper reports the development of three separate assays based on reversed phase high-per...Xiao-xu-ming decoction(XXMD)is a traditional Chinese medicine that has been widely used to treat theoplegia and its sequelae.This paper reports the development of three separate assays based on reversed phase high-performance liquid chromatography–mass spectrometry(HPLC–MS)and HPLC–MS/MS for the determination of seven active constituents of XXMD viz oroxylin A-7-O-glucuronide,wogonoside,liquiritigenin,cimifugin,5-O-methylvisammiol,glycyrrhizic acid and glycyrrhetinic acid in rat plasma.All calibration curves were linear(r >0.99)with lower limits of quantitation(LLOQs)<12.4 ng/mL.Intra-and inter-day precisions(as relative standard deviation)were all <10.7% with recoveries in the range of 88.7–113%.In addition,the seven analytes were shown to be stable in rat plasma samples under relevant storage conditions.The validated methods were successfully applied to a pharmacokinetic study in rat after oral administration of XXMD.展开更多
Ischemic stroke seriously threatens human health and quality of life.Xiao-Xu-Ming(XXM)decoction has been a classical prescription for stroke therapy.In our previous studies,we have found that XXM exerts neuroprotectiv...Ischemic stroke seriously threatens human health and quality of life.Xiao-Xu-Ming(XXM)decoction has been a classical prescription for stroke therapy.In our previous studies,we have found that XXM exerts neuroprotective effects,improves brain injury,and attenuates neuroinflammation in cerebral ischemia rats.In this study,we investigated the effects and possible mechanism of XXM on thrombotic focal cerebral ischemia.After treatment with XXM,the neurological function and motor abilities were improved,and cerebral infarction volume was significantly decreased compared with rats of thrombotic focal cerebral ischemia.Besides,the results of BBB integrity detected by EB leakage and tight junction(TJ)protein expression showed that XXM could maintain BBB integrity and improve the expressions of TJ proteins,including claudin-1,occluding,and ZO-1,in the ischemic ipsilateral cortex disrupted by thrombotic cerebral ischemia.Furthermore,proteomic techniques were used to identify the differentially expressed proteins(DEPs)in the ischemic cerebral cortex,and the results showed that 132 DEPs regulated by XXM were detected in the ischemic cerebral cortex.Bioinformatic analysis showed that these regulated proteins by XXM were mainly involved in complement and coagulation cascade,and lysosome,etc.Furthermore,there was an interaction among DEPs,including Lgals3,Ctsz,Capg,C1qa,S100a4,Grn,Hspb1,Aif1,and Anxa1,etc.In conclusion,XXM ameliorated brain injury of thrombotic focal ischemic stroke,and Lgals3,Ctsz,Capg,C1qa,S100a4,Grn,Hspb1,Aif1,and Anxa1 could help provide possible therapeutic targets of XXM for ischemic stroke and offer research direction for further research.展开更多
Stroke is a major cause of severe disability and death.Xiao-Xu-Ming decoction(XXMD)is an effective prescription for stroke and its sequelae,while its effective ingredients and mechanism are still unclear.In the presen...Stroke is a major cause of severe disability and death.Xiao-Xu-Ming decoction(XXMD)is an effective prescription for stroke and its sequelae,while its effective ingredients and mechanism are still unclear.In the present study,we aimed to explore the effective ingredients and mechanism of XXMD in treating cerebral ischemia using network pharmacology.The main chemical components and targets of 12 herbs of XXMD were obtained by the TCMSP database and analysis platform database.The active components in XXMD were screened according to oral utilization and drug-like properties.Then,the cerebral ischemia targets were obtained through GeneCards,OMIM,TTD,Diligent and Drugbank databases.We analyzed the pathophysiological processes and pathways involved in the treatment of cerebral ischemia with XXMD by using the Metascape data analysis platform.Results showed thatβ-sitosterol,kaempferol,quercetin,stigmasterol,wogonin,and catechins might be the potential core active ingredients of XXMD in the treatment of cerebral ischemia.The therapeutic effect of XXMD on stroke was mainly exerted through regulating neuroinflammatory response and neurovascular protection.Furthermore,the anti-neuroinflammation and neurovascular protection of XXMD were further confirmed using cerebral ischemia rats.Collectively,our findings revealed that the mechanism of XXMD on the treatment of cerebral ischemia was related to anti-neuroinflammation and neurovascular protection.展开更多
Xiao-Xu-Ming decoction(XXMD) was a traditional Chinese prescription and first recorded in "Bei Ji Qian Jin Yao Fang".It has been widely used to treat theoplegia and the sequel of theoplegia in China.In the present...Xiao-Xu-Ming decoction(XXMD) was a traditional Chinese prescription and first recorded in "Bei Ji Qian Jin Yao Fang".It has been widely used to treat theoplegia and the sequel of theoplegia in China.In the present work,high-performance liquid chromatography coupled with high resolution mass spectrometry(HPLC-HRMS) combined with the mass spectral tree similarity filter technique(MTSF)was used to rapidly discover and identify the compounds of the active fraction of XXMD.A total of 3362 compounds were automatically detected by HPLC-HRMS,and final 68 compounds were identified in the active fraction of XXMD.including 14 templated compounds(reference compounds),50 related compounds fished by MTSF technique,and 4 unrelated compounds identified by manual method.This study successfully applied MTSF technology for the first time to discover and identify the components of Chinese prescription.The results demonstrated that MTSF technique should be useful to the discovery and identification of compounds in Chinese prescription.This study also proved that MTSF can be applied to the targeted phytochemical separation.展开更多
BACKGROUND Helicobacter pylori(HP),the most common pathogenic microorganism in stomach,can induce inflammatory reactions in the gastric mucosa,causing chronic gastritis and even gastric cancer.HP infection affects ove...BACKGROUND Helicobacter pylori(HP),the most common pathogenic microorganism in stomach,can induce inflammatory reactions in the gastric mucosa,causing chronic gastritis and even gastric cancer.HP infection affects over 4.4 billion people globally,with a worldwide infection rate of up to 50%.The multidrug resistance of HP poses a serious challenge to eradication.It has been monstrated that compared to bismuth quadruple therapy,Qingre Huashi decoction(QHD)combined with triple therapy exhibits comparable eradication rates but with a lower incidence of adverse reactions;in addition,QHD directly inhibit and kill HP in vitro.METHODS In this study,12 HP strains were isolated in vitro after biopsy during gastroscopy of HP-infected patients.In vitro,the minimum inhibitory concentration(MIC)values for clinical HP strains and biofilm quantification were determined through the E-test method and crystal violet staining,respectively.The most robust biofilm-forming strain of HP was selected,and QHD was evaluated for its inhibitory and bactericidal effects on the strain with strong biofilm formation.This assessment was performed using agar dilution,E-test,killing dynamics,and transmission electron microscopy(TEM).The study also explored the impact of QHD on antibiotic resistance in these HP strains with strong biofilm formation.Crystalline violet method,scanning electron microscopy,laser confocal scanning microscopy,and(p)ppGpp chromatographic identification were employed to evaluate the effect of QHD on biofilm in strong biofilm-forming HP strains.The effect of QHD on biofilm and efflux pump-related gene expression was evaluated by quantitative polymerase chain reaction.Non-targeted metabolomics with UHPLC-MS/MS was used to identify potential metabolic pathways and biomarkers which were different between the NC and QHD groups.RESULTS HP could form biofilms of different degrees in vitro,and the intensity of formation was associated with the drug resistance of the strain.QHD had strong bacteriostatic and bactericidal effects on HP,with MICs of 32-64 mg/mL.QHD could inhibit the biofilm formation of the strong biofilm-forming HP strains,disrupt the biofilm structure,lower the accumulation of(p)ppGpp,decrease the expression of biofilm-related genes including LuxS,Spot,glup(HP1174),NapA,and CagE,and reduce the expression of efflux pump-related genes such as HP0605,HP0971,HP1327,and HP1489.Based on metabolomic analysis,QHD induced oxidative stress in HP,enhanced metabolism,and potentially inhibited relevant signaling pathways by upregulating adenosine monophosphate(AMP),thereby affecting HP growth,metabolism,and protein synthesis.CONCLUSION QHD exerts bacteriostatic and bactericidal effects on HP,and reduces HP drug resistance by inhibiting HP biofilm formation,destroying its biofilm structure,inhibiting the expression of biofilm-related genes and efflux pump-related genes,enhancing HP metabolism,and activating AMP in HP.展开更多
BACKGROUND Cancer is one of the most serious threats to human health worldwide.Conventional treatments such as surgery and chemotherapy are associated with some drawbacks.In recent years,traditional Chinese medicine t...BACKGROUND Cancer is one of the most serious threats to human health worldwide.Conventional treatments such as surgery and chemotherapy are associated with some drawbacks.In recent years,traditional Chinese medicine treatment has been increasingly advocated by patients and attracted attention from clinicians,and has become an indispensable part of the comprehensive treatment for gastric cancer.AIM To investigate the mechanism of Xiaojianzhong decoction(XJZ)in the treatment of gastric cancer(GC)by utilizing network pharmacology and experimental validation,so as to provide a theoretical basis for later experimental research.METHODS We analyzed the mechanism and targets of XJZ in the treatment of GC through network pharmacology and bioinformatics.Subsequently,we verified the impact of XJZ treatment on the proliferative ability of GC cells through CCK-8,apoptosis,cell cycle,and clone formation assays.Additionally,we performed Western blot analysis and real-time quantitative PCR to assess the protein and mRNA expression of the core proteins.RESULTS XJZ mainly regulates IL6,PTGS2,CCL2,MMP9,MMP2,HMOX1,and other target genes and pathways in cancer to treat GC.The inhibition of cell viability,the increase of apoptosis,the blockage of the cell cycle at the G0/G1 phase,and the inhibition of the ability of cell clone formation were observed in AGS and HGC-27 cells after XJZ treatment.In addition,XJZ induced a decrease in the mRNA expression of IL6,PTGS2,MMP9,MMP2,and CCL2,and an increase in the mRNA expression of HOMX1.XJZ significantly inhibited the expression of IL6,PTGS2,MMP9,MMP2,and CCL2 proteins and promoted the expression of the heme oxygenase-1 protein.CONCLUSION XJZ exerts therapeutic effects against GC through multiple components,multiple targets,and multiple pathways.Our findings provide a new idea and scientific basis for further research on the molecular mechanisms underlying the therapeutic effects of XJZ in the treatment of GC.展开更多
Objective To explore the influence of Linggui Zhugan Decoction(LGZGD) on high glucose induced podocyte autophagy.Methods LGZGD containing serum was prepared by intragastric administation of 4.2 g/kg(low dose), 8.4 g/k...Objective To explore the influence of Linggui Zhugan Decoction(LGZGD) on high glucose induced podocyte autophagy.Methods LGZGD containing serum was prepared by intragastric administation of 4.2 g/kg(low dose), 8.4 g/kg(medium dose), and 12.6 g/kg(high dose) LGZGD into SD rats respectively. MPC5 and AB8/13 podocyte cells were treated with 60 mmol/L glucose to establish diabetic nephropathy podocyte model in vitro. Both podocytes were divided into control group, high glucose group, low dose LGZGD group, medium dose LGZGD group, and high dose LGZGD group, respectively. For the three LGZGD groups, before LGZGD intervention, podocytes were treated with 60 mmol/L glucose for 3 days. After treated with LGZGD containing serum, cells were collected to analyze cell migration using Transwell assay, proliferation using CCK8, apoptosis and cell cycle using flow cytometry, autophagosome formation using transmission electron microscopy, and expression levels of Beclin-1, Atg5, LC3II/I, and P62 proteins using Western blot.Results Compared with the control group, the proliferation and migration of MPC5 and AB8/13 cells in the high glucose group slightly decreased, whereas these parameters restored after intervention with low and medium concentrations of LGZGD, with the medium dose LGZGD having the better effect(P < 0.05). Flow cytometry showed that the medium dose LGZGD group had a significantly lower apoptosis rate(P < 0.05) and higher survival rate(P > 0.05) compared to the high dose LGZGD group. High glucose arrested podocytes in G1 phase, whereas LGZGD shifted podocytes from being predominant in G1 phase to G2 phase. High dose LGZGD significanly reduced high glucose-increased autophagosome formation in both podocytes(P < 0.05). Western blot analysis showed that Beclin-1, Atg5, LC3II/I, and P62 expressions were increased in MPC5 cells treated with high glucose and reversed after adminstration of low and medium doses of LGZGD(P < 0.05).Conclusion LGZGD reduced apoptosis and enhanced autophagy in high glucose treated podocytes via regulating Beclin-1/LC3II/I/Atg5 expression.展开更多
[Objectives]To explore the effects of Shentong Zhuyu decoction combined with massage therapy in the treatment of exertional chronic lumbar muscle strain.[Methods]Sixty-four cases of exertional chronic lumbar muscle st...[Objectives]To explore the effects of Shentong Zhuyu decoction combined with massage therapy in the treatment of exertional chronic lumbar muscle strain.[Methods]Sixty-four cases of exertional chronic lumbar muscle strain were randomly divided into two groups(32 cases each group).The patients in the control group only took celecoxib capsules,and those in the treatment group additionally took Shentong Zhuyu decoction combined with massage therapy.TCM syndrome score,lumbar function,hemorrheology index and clinical effect were compared between the two groups before and after treatment.[Results]After treatment,the TCM syndrome scores of lumbar distension/dull pain,tingling-like lumbago,adverse lateral turn,body weight loss,dark purple tongue,slow or astringent pulse,and Oswestry disability index(ODI)score in the treatment group were lower than those in the control group,and the levels of plasma viscosity,red blood cell aggregation index,platelet aggregation rate(PAG)and fibrinogen(Fib)were lower than those in the control group,showing statistical significance(P<0.05).The overall clinical effect distribution of the treatment group was better than that of the control group,and the difference was statistically significant(P<0.05).[Conclusions]Shentong Zhuyu decoction combined with massage therapy can effectively relieve the symptoms of patients with lumbago and improve the lumbar mobility function and hemorrheology,with obvious therapeutic effects in the treatment of exertional chronic lumbar muscle strain.展开更多
Objective:To investigate the potential mechanism of Wendan decoction in obesity by screening target genes with promoter region methylation changes and constructing a multiple signaling pathways network based on promot...Objective:To investigate the potential mechanism of Wendan decoction in obesity by screening target genes with promoter region methylation changes and constructing a multiple signaling pathways network based on promoter methylation.Methods:The methylation degree of Itgad,Col8a1,Adra2b,Jund,Rab2a,Wnt8b,Fzd9,B4galt7,Pik3cd,Creb1,Stard8,and Mmp1 in the abdominal adipose tissue of obese rats was determined using the Agena MassARRAY system.Western blot was performed to assess protein expression levels.Target genes were identified based on the methylation degree in the promoter region and protein expression.Enrichment analysis of signaling pathways was conducted to identify relevant target genes and obtain a multiple signaling pathway network associated with obesity.Core and terminal effector molecules in the pathway networks were selected as research targets for reverse transcription-polymerase chain reaction(RT-PCR)analysis.Results:Four genes(Adra2b,Creb1,Itgad,and Pik3cd)showed a degree of promoter methylation consistent with their respective protein expression levels.Among them,Adra2b,Creb1,and Pik3cd expression increased,while that of Itgad decreased.Enrichment analysis revealed that Creb1 and Pik3cd were involved in 6 signaling pathways related to obesity:tumor necrosis factor(TNF)signaling pathway,growth hormone synthesis/secretion and action,adenosine 5'-monophosphate-activated protein kinase(AMPK)signaling pathway,relaxin signaling pathway,cyclic nucleotide(cAMP)signaling pathway,and phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt)signaling pathway.Subsequently,a multiple signaling pathways network was constructed based on promoter methylation.Key molecules including protein kinase B(AKT),mechanistic target of rapamycin complex 1(mTORC1),and unc-51 like autophagy activating kinase 1(ULK1),as well as terminal effector molecules interleukin-1β(IL-1β),interleukin-6(IL-6),and chemokine(C-X-C motif)ligand 2(CXCL2)were selected as research targets.Wendan decoction decreased the expressions of AKT,mTORC1,IL-1β,IL-6,and CXCL2 while up-regulating ULK1 expression.Conclusion:The mechanism of Wendan decoction in preventing obesity involves the regulation of multiple signaling pathways through the control of Creb1 and Pik3cd gene promoter methylation.However,the associated multi-path gene regulation mechanism in preventing obesity is complex.Thus,further exploration is needed to elucidate the role of methylation changes in this mechanism.展开更多
[Objectives]To investigate the effect and mechanism of Dachengqi Decoction and separated decoction on incomplete intestinal obstruction in rats.[Methods]80 healthy SD rats were selected to establish incomplete intesti...[Objectives]To investigate the effect and mechanism of Dachengqi Decoction and separated decoction on incomplete intestinal obstruction in rats.[Methods]80 healthy SD rats were selected to establish incomplete intestinal obstruction model by silk ligation.The dosage was 20 mL/kg for 3 d,and the damage index of ileocecal mucosa was analyzed;the morphology of ileocecal mucosa was observed by HE staining;the serum levels of IL-1α,IL-1β,IL-6,IL-18,Ach,NO,ET,IL-1,TNF-αand ultra-micro Na+-K+-ATPase were detected by ELISA.[Results]Compared with the model group,the mucosal damage index of Dachengqi Decoction and each separated decoction group decreased significantly(P<0.05);compared with the normal group and sham operation group,the serum level of IL-1,IL-6,TNF-αand other factors in the model group increased significantly(P<0.05);compared with the model group,the serum IL-1,IL-6 and TNF-αsecretion levels of rats in Dachengqi Decoction group and separated decoction group decreased(P<0.01).[Conclusions]Dachengqi Decoction and each separated decoction can effectively improve intestinal tissue pathological damage in the incomplete intestinal obstruction model rats,and reduce the inflammatory reaction in the rat body.展开更多
During the late Qing dynasty(1840 A.D.-1912 A.D.),a large quantity of Western medicines entered China,which continuously impacted the traditional Chinese medicine(TCM)market and revealed the shortcomings of Chinese me...During the late Qing dynasty(1840 A.D.-1912 A.D.),a large quantity of Western medicines entered China,which continuously impacted the traditional Chinese medicine(TCM)market and revealed the shortcomings of Chinese medicines.Some personages in the TCM community followed the trend of learning from the West,and attempted to reform TCM,with the improvement on decoction becoming an important aspect of this effort.Through debates and trials,the improvement on decoction underwent three stages of conceptual evolution:“taking Chinese medicines as the foundation and referring to the dosage forms of Western medicines”,“introducing Western techniques to serve the preparation of decoctions”and“integrating the theories of TCM and Western medicine to improve decoctions”.The study highlights the effective complementarity between modern TCM and Western medicine in the field of pharmacy,and provides valuable experience and support for the reevaluation of the value of TCM in contemporary society.展开更多
Objective:To uncover the underlying mechanisms of action of the Yinlai decoction on high-calorie dietinduced pneumonia through proteomics analysis.Methods:Based on the Gene Expression Omnibus(GEO)database,lung tissue ...Objective:To uncover the underlying mechanisms of action of the Yinlai decoction on high-calorie dietinduced pneumonia through proteomics analysis.Methods:Based on the Gene Expression Omnibus(GEO)database,lung tissue samples from normal and high-fat diet(HFD)fed mice in the GSE16377 dataset were selected as test cohorts to identify differentially expressed genes and conduct bioinformatics analyses.In the animal experiments,mice were randomly divided into the control(N),high-calorie diet pneumonia(M),and Yinlai decoction treatment(Y)groups.Mice in the M group received high-calorie feed and a 0.5 mg/mL lipopolysaccharide solution spray for 30 min for 3 d.The mice in the Y group were intragastrically administered 2 mL/10 g Yinlai decoction twice daily for 3 d.Pathological evaluation of the lung tissue was performed.Differentially expressed proteins(DEPs)in the lung tissue were identified using quantitative proteomics and bioinformatics analyses.The drug-target relationships between Yinlai decoction and core DEPs in the lung tissue were verified using AutoDock Vina and Molecular Graphics Laboratory(MGL)Tools.DEPs were verified by western blot.Results:GEO data mining showed that an HFD altered oxidative phosphorylation in mouse lung tissue.The Yinlai decoction alleviated pathological damage to lung tissue and pneumonia in mice that were fed a high-calorie diet.A total of 47 DEPs were identified between the Y and M groups.Enrichment analysis revealed their association with energy metabolism pathways such as the tricarboxylic acid cycle(TCA)and oxidative phosphorylation.The protein-protein interaction network revealed that Atp5a1,Pdha1,and Sdha were the target proteins mediating the therapeutic effects of Yinlai decoction.Molecular docking results suggested that the mechanism of the therapeutic effect of Yinlai decoction involves the binding of brassinolide,praeruptorin B,chrysoeriol,and other components in Yinlai decoction to Atp5a1.Conclusion:The Yinlai decoction alleviated lung tissue damage and pneumonia in mice that were fed a high-calorie diet by regulating the TCA and oxidative phosphorylation.Our study highlights the importance of a healthy diet for patients with pneumonia and provides a scientific basis for the prevention and treatment of pneumonia through dietary adjustments.展开更多
Objective:To systematically evaluate the long-term efficacy of Bushen Huoxue Decoction combined with vertebroplasty(PVP or PKP)in the treatment of osteoporotic vertebral compression fractures(OVCF),in order to provide...Objective:To systematically evaluate the long-term efficacy of Bushen Huoxue Decoction combined with vertebroplasty(PVP or PKP)in the treatment of osteoporotic vertebral compression fractures(OVCF),in order to provide evidence-based reference for clinical application.Methods:To ensure the novelty of research data,a computer search was conducted between 2017 and February 2023 to publicly publish all randomized controlled studies and clinical trials at home and abroad on the treatment of OVCF with Bushen Huoxue Decoction combined with vertebroplasty published in CNKI,Wanfang,Vip,PubMed,CBM,and Cochrane libraries.Two researchers independently conducted literature screening and data extraction,evaluated the quality of randomized controlled trials included one by one according to the Cochrane collaboration network standards,and conducted a meta statistical analysis using RevMan5.3 for studies that met the inclusion criteria.Results:A total of 684 patients were included in 7 randomized controlled trials,including 342 patients in the observation group and 342 patients in the control group,with a ratio of 1:1;The meta-analysis results showed that in the observation group,the overall effective rate[RR=1.30,95%CI(1.14,1.47),P<0.001],visual analog pain(VAS)score[SMD=1.19,95%CI(0.77,1.61),P<0.0001],bone mineral density score[SMD=1.09,95%CI(0.15,2.04),P=0.02],COQOL score[SMD=0.99,95%CI(0.68,1.30),P<0.00001],OPG score[SMD=0.48,95%CI(0.18,0.77),P=0.002]The RANKL score[SMD=1.33,95%CI(1.00,1.65),P<0.0001]was significantly superior to the control group,with statistically significant differences.There was no significant difference in the Oswestry Disability Index(ODI)score[SMD=0.27,95%CI(-0.03,0.57),P=0.08],Cobb score[SMD=1.52,95%CI(-1.05,4.09),P=0.25],and vertebral height score[SMD=0.43,95%CI(-0.14,1.01),P=0.14].Conclusion:The results show that Bushen Huoxue Decoction combined with vertebroplasty has significant advantages in improving bone mineral density and alleviating pain in patients after OVCF,which is significantly superior to using OVCF alone.展开更多
Objective: To investigate the differential expression of miRNA and related biological functions and signaling pathways after the intervention of the THP-1-derived foam cell model with the drug-containing serum of Yima...Objective: To investigate the differential expression of miRNA and related biological functions and signaling pathways after the intervention of the THP-1-derived foam cell model with the drug-containing serum of Yimaijiangzhi Decoction. Methods: The experiment was divided into macrophage group, foam cell model group and Yimaijiangzhi drug-containing serum group. THP-1 cells were induced into macrophages by Fopol ester, and induced differentiated macrophages were given ox-LDL to establish foam cell model, and Yimaijiangzhi decoction rat serum was used to intervene the foam cells. Total RNA was extracted from cells in each group for miRNA sequencing, differential expression of miRNA was screened, and relevant target genes were predicted for GO analysis and KEGG analysis, protein interaction network and miRNA-target gene interaction network were established, and RT-qPCR was used to verify the possible signaling pathways for improving atherosclerosis. Result: The difference miRNA between blank group and model group was hsa-miR-302c-3p, hsa-miR-302d-3p, hsa- mir-30d-3p, hsa-mir-3189-3p, hsa-mir-374b-5p, hsa-mir-423-5p, hsa-mir-423-5p, and hsa- mir-4781-3p, hsa-mir-663a;The miRNAs of model group and Yimaijiangzhi drug-containing serum group were hsa-mir-3150a-3p, hsa-mir-7704, hsa-mir-887-3p, hsa-mir-150-5p, hsa- mir-423-5p, hsa-mir-374c-3p, hsa-mir-374c-3p, hsa-mir-374b-5p;The difference of miRNAs prediction target genes between model group and Yimaijiangzhi drug-containing serum group showed that the miRNA prediction target genes were mainly enriched in MAPK signaling pathway, ErbB signaling pathway, Hippo signaling pathway, Wnt signaling pathway and other signaling pathways. SCN1A, PRKACA, MECP2, EIF4E, SRSF1, MBNL1, PRKCA, PPARGC1A may be the potential key targets for the effect of the drug-containing serum of Yimaijiangzhi Decoction on THP-1-derived foam cells. Conclusion: hsa-mir-374c-3p, hsa- mir-423-5p, and hsa-mir-374b-5p are important miRNAs that the drug-containing serum of Yimaijiangzhi Decoction acts on foam cells. The significantly differentially expressed mirnas and significantly enriched related signaling pathways may provide new ideas for the diagnosis and treatment of atherosclerosis.展开更多
Background:Sanhua decoction has significant effects in the treatment of stroke.The study of the Sanhua decoction material benchmark was carried out to analyze the value transfer relationship between the Chinese herbal...Background:Sanhua decoction has significant effects in the treatment of stroke.The study of the Sanhua decoction material benchmark was carried out to analyze the value transfer relationship between the Chinese herbal pieces and the substance benchmark.Methods:Network pharmacology was employed to investigate the potential active components and molecular mechanisms of Sanhua decoction in the treatment of stroke.15 batches of Sanhua decoction lyophilized powder were prepared using traditional formulas and subjected to high-performance liquid chromatography analysis to generate fingerprints of the Sanhua decoction substance benchmarks.Then,a multi-component quantitative analysis method was established,allowing for the simultaneous determination of ten components,to study the transfer of quantity values between pieces and substance benchmarks.Results:60 active ingredients were screened from Sanhua decoction by network pharmacology,of which gallic acid,magnolol honokiol,physcion,and aloe-emodin may have a greater effect than other active components.63 key targets and 134 pathways were predicted as the potential mechanism of Sanhua decoction in treating stroke.The fingerprint similarity of the Sanhua decoction substance benchmarks was found to be good among the 15 batches,confirming the 19 common peaks.The content of the 10 components was basically consistent.The components’transfer rates were within 30%of their respective means.Conclusions:This study provided a comprehensive and reliable strategy for the quality evaluation of Sanhua decoction substance benchmarks and held significant importance in improving its application value.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 in part by the National Natural Science Foundation of China,No.81473383(to YHW)the Significant New-Drugs Creation of Science and Technology Major Projects in China,No.2018ZX09711001-003-019(to YHW)the Innovation Fund for Graduate of Beijing Union Medical College of China,No.2017-1007-02(to XC)
文摘Xiao-Xu-Ming decoction has been widely used to treat stroke and sequelae of stroke. We have previously shown that the active fractions of Xiao-Xu-Ming decoction attenuate cerebral ischemic injury. However, the global protein profile and signaling conduction pathways regulated by Xiao-Xu-Ming decoction are still unclear. This study established a two-vessel occlusion rat model by bilateral common carotid artery occlusion. Rats were intragastrically administered 50 or 150 mg/kg Xiao-Xu-Ming decoction for 4 consecutive weeks. Learning and memory abilities were measured with Morris water maze. Motor ability was detected with prehensile test. Coordination ability was examined using the inclined screen test. Neuronal plasticity was observed by immunofluorescent staining. Differentially expressed proteins of rat hippocampus were analyzed by label-free quantitative proteomics. Real time-polymerase chain reaction and western blot assay were used to identify the changes in proteins. Results showed that Xiao-Xu-Ming decoction dramatically alleviated learning and memory deficits, and motor and coordination dysfunction, and increased the expression of microtubule-associated protein 2. Xiao-Xu-Ming decoction extract remarkably decreased 13 upregulated proteins and increased 39 downregulated proteins. The regulated proteins were mainly involved in oxidation reduction process, intracellular signaling cascade process, and protein catabolic process. The signaling pathways were mainly involved in ubiquitin mediated proteolysis and the phosphatidylinositol signaling system. Furthermore, there was an interaction among Rab2 a, Ptpn1, Ppm1 e, Cdk18, Gorasp2, Eps15, Capza2, Syngap1 and Mt-nd1. Protein analyses confirmed the changes in expression of MTND1. The current findings provide new insights into the molecular mechanisms of Xiao-Xu-Ming decoction extract's effects on chronic cerebral hypoperfusion.
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 National Natural Science Foundation of China(Grant No.81473383)the Innovation Fund for Graduate of Beijing Union Medical College(Grant No.2017-1007-02)+1 种基金the Drug Innovation Major Project(Grant No.2018ZX09711001-003-019)the Medical and Health Innovation Project of Chinese Academy of Medical Sciences(Grant No.2016-I2M-3-007,2018-1007-04)
文摘In the present study, we aimed to investigate the effects of Xiao-Xu-Ming decoction extract(XXM) on lipopolysaccaride(LPS)-induced neuroinflammation in vitro and in vivo. In vitro, the microglia BV2 cells were treated with 200 ng/mL LPS for 24 h to induce inflammatory responses. In vivo, mice were treated with 5 mg/kg LPS to induce inflammatory responses. The NO level was determined by Griess Reagents. The levels of IL-1β, IL-6, TNF-α and MCP-1 were determined by ELISA. The expressions of Iba-1, TLR4 and MyD88 at the protein levels were determined by Western blotting analysis. The mRNA levels of TLR4 and MyD88 were determined by real-time PCR. In vitro, XXM significantly reduced the levels of various pro-inflammatory factors, including NO, IL-1β, IL-6 and TNF-α, induced by LPS in the supernatant of BV2 cells and suppressed expressions of inflammatory proteins TLR4 and MyD88 induced by LPS in BV2 cells. In vivo, XXM significantly inhibited microglia activation, attenuated LPS-induced inflammatory factors and chemokine production, such as IL-1β, IL-6, TNF-α and MCP-1, and inhibited the expressions of inflammatory proteins including TLR4 and MyD88, in the cortex of LPS-induced mice. Our findings suggested that XXM could attenuate LPS-induced neuroinflammation via down-regulating TLR4/MyD88 signaling pathway.
基金the National Natural Science Foundation of China(No.30630073)the Innovation Method Fund from Ministry of Science and Technology of China(2009IM031600)for financial support.
文摘Xiao-xu-ming decoction(XXMD)is a traditional Chinese medicine that has been widely used to treat theoplegia and its sequelae.This paper reports the development of three separate assays based on reversed phase high-performance liquid chromatography–mass spectrometry(HPLC–MS)and HPLC–MS/MS for the determination of seven active constituents of XXMD viz oroxylin A-7-O-glucuronide,wogonoside,liquiritigenin,cimifugin,5-O-methylvisammiol,glycyrrhizic acid and glycyrrhetinic acid in rat plasma.All calibration curves were linear(r >0.99)with lower limits of quantitation(LLOQs)<12.4 ng/mL.Intra-and inter-day precisions(as relative standard deviation)were all <10.7% with recoveries in the range of 88.7–113%.In addition,the seven analytes were shown to be stable in rat plasma samples under relevant storage conditions.The validated methods were successfully applied to a pharmacokinetic study in rat after oral administration of XXMD.
基金The National Natural Science Foundation of China (Grant No. 81473383)the Significant New-Drugs Creation of Science and Technology Major Projects (Grant No. 2018ZX09711001-003-019)+1 种基金the Medical and Health Innovation Project of Chinese Academy of Medical Sciences (Grant No. 2016-I2M-3-007)Innovation Fund for Graduate of Beijing Union Medical College (Grant No. 2018-1007-04)。
文摘Ischemic stroke seriously threatens human health and quality of life.Xiao-Xu-Ming(XXM)decoction has been a classical prescription for stroke therapy.In our previous studies,we have found that XXM exerts neuroprotective effects,improves brain injury,and attenuates neuroinflammation in cerebral ischemia rats.In this study,we investigated the effects and possible mechanism of XXM on thrombotic focal cerebral ischemia.After treatment with XXM,the neurological function and motor abilities were improved,and cerebral infarction volume was significantly decreased compared with rats of thrombotic focal cerebral ischemia.Besides,the results of BBB integrity detected by EB leakage and tight junction(TJ)protein expression showed that XXM could maintain BBB integrity and improve the expressions of TJ proteins,including claudin-1,occluding,and ZO-1,in the ischemic ipsilateral cortex disrupted by thrombotic cerebral ischemia.Furthermore,proteomic techniques were used to identify the differentially expressed proteins(DEPs)in the ischemic cerebral cortex,and the results showed that 132 DEPs regulated by XXM were detected in the ischemic cerebral cortex.Bioinformatic analysis showed that these regulated proteins by XXM were mainly involved in complement and coagulation cascade,and lysosome,etc.Furthermore,there was an interaction among DEPs,including Lgals3,Ctsz,Capg,C1qa,S100a4,Grn,Hspb1,Aif1,and Anxa1,etc.In conclusion,XXM ameliorated brain injury of thrombotic focal ischemic stroke,and Lgals3,Ctsz,Capg,C1qa,S100a4,Grn,Hspb1,Aif1,and Anxa1 could help provide possible therapeutic targets of XXM for ischemic stroke and offer research direction for further research.
基金National Natural Science Foundation of China(Gr ant No.81473383)the Medical and Health Innovation Project o Chinese Academy of Medical Sciences(Grant No.2016-I2M-3-007)Innovation Fund for Graduate of Beijing Union Medical College(Grant No.2018-1007-04)。
文摘Stroke is a major cause of severe disability and death.Xiao-Xu-Ming decoction(XXMD)is an effective prescription for stroke and its sequelae,while its effective ingredients and mechanism are still unclear.In the present study,we aimed to explore the effective ingredients and mechanism of XXMD in treating cerebral ischemia using network pharmacology.The main chemical components and targets of 12 herbs of XXMD were obtained by the TCMSP database and analysis platform database.The active components in XXMD were screened according to oral utilization and drug-like properties.Then,the cerebral ischemia targets were obtained through GeneCards,OMIM,TTD,Diligent and Drugbank databases.We analyzed the pathophysiological processes and pathways involved in the treatment of cerebral ischemia with XXMD by using the Metascape data analysis platform.Results showed thatβ-sitosterol,kaempferol,quercetin,stigmasterol,wogonin,and catechins might be the potential core active ingredients of XXMD in the treatment of cerebral ischemia.The therapeutic effect of XXMD on stroke was mainly exerted through regulating neuroinflammatory response and neurovascular protection.Furthermore,the anti-neuroinflammation and neurovascular protection of XXMD were further confirmed using cerebral ischemia rats.Collectively,our findings revealed that the mechanism of XXMD on the treatment of cerebral ischemia was related to anti-neuroinflammation and neurovascular protection.
基金the Natural Science Foundation of Beijing(No.7133252) for financial support of this work
文摘Xiao-Xu-Ming decoction(XXMD) was a traditional Chinese prescription and first recorded in "Bei Ji Qian Jin Yao Fang".It has been widely used to treat theoplegia and the sequel of theoplegia in China.In the present work,high-performance liquid chromatography coupled with high resolution mass spectrometry(HPLC-HRMS) combined with the mass spectral tree similarity filter technique(MTSF)was used to rapidly discover and identify the compounds of the active fraction of XXMD.A total of 3362 compounds were automatically detected by HPLC-HRMS,and final 68 compounds were identified in the active fraction of XXMD.including 14 templated compounds(reference compounds),50 related compounds fished by MTSF technique,and 4 unrelated compounds identified by manual method.This study successfully applied MTSF technology for the first time to discover and identify the components of Chinese prescription.The results demonstrated that MTSF technique should be useful to the discovery and identification of compounds in Chinese prescription.This study also proved that MTSF can be applied to the targeted phytochemical separation.
基金Supported by the National Natural Science Foundation of China,No.81973615 and No.82304930Natural Science Foundation of Beijing,No.7332323Capital’s Funds for Health Improvement and Research,No.CF2022-2-40711.
文摘BACKGROUND Helicobacter pylori(HP),the most common pathogenic microorganism in stomach,can induce inflammatory reactions in the gastric mucosa,causing chronic gastritis and even gastric cancer.HP infection affects over 4.4 billion people globally,with a worldwide infection rate of up to 50%.The multidrug resistance of HP poses a serious challenge to eradication.It has been monstrated that compared to bismuth quadruple therapy,Qingre Huashi decoction(QHD)combined with triple therapy exhibits comparable eradication rates but with a lower incidence of adverse reactions;in addition,QHD directly inhibit and kill HP in vitro.METHODS In this study,12 HP strains were isolated in vitro after biopsy during gastroscopy of HP-infected patients.In vitro,the minimum inhibitory concentration(MIC)values for clinical HP strains and biofilm quantification were determined through the E-test method and crystal violet staining,respectively.The most robust biofilm-forming strain of HP was selected,and QHD was evaluated for its inhibitory and bactericidal effects on the strain with strong biofilm formation.This assessment was performed using agar dilution,E-test,killing dynamics,and transmission electron microscopy(TEM).The study also explored the impact of QHD on antibiotic resistance in these HP strains with strong biofilm formation.Crystalline violet method,scanning electron microscopy,laser confocal scanning microscopy,and(p)ppGpp chromatographic identification were employed to evaluate the effect of QHD on biofilm in strong biofilm-forming HP strains.The effect of QHD on biofilm and efflux pump-related gene expression was evaluated by quantitative polymerase chain reaction.Non-targeted metabolomics with UHPLC-MS/MS was used to identify potential metabolic pathways and biomarkers which were different between the NC and QHD groups.RESULTS HP could form biofilms of different degrees in vitro,and the intensity of formation was associated with the drug resistance of the strain.QHD had strong bacteriostatic and bactericidal effects on HP,with MICs of 32-64 mg/mL.QHD could inhibit the biofilm formation of the strong biofilm-forming HP strains,disrupt the biofilm structure,lower the accumulation of(p)ppGpp,decrease the expression of biofilm-related genes including LuxS,Spot,glup(HP1174),NapA,and CagE,and reduce the expression of efflux pump-related genes such as HP0605,HP0971,HP1327,and HP1489.Based on metabolomic analysis,QHD induced oxidative stress in HP,enhanced metabolism,and potentially inhibited relevant signaling pathways by upregulating adenosine monophosphate(AMP),thereby affecting HP growth,metabolism,and protein synthesis.CONCLUSION QHD exerts bacteriostatic and bactericidal effects on HP,and reduces HP drug resistance by inhibiting HP biofilm formation,destroying its biofilm structure,inhibiting the expression of biofilm-related genes and efflux pump-related genes,enhancing HP metabolism,and activating AMP in HP.
基金West Light Foundation of the Ningxia Key Research and Development Program,No.2023BEG02015High-level Key Discipline Construction Project of State Administration of Traditional Chinese Medicine,No.2022-226+1 种基金Talent Development Projects of Young Qihuang of National Administration of Traditional Chinese Medicine,No.2020-218National Natural Science Foundation of China,No.82374261.
文摘BACKGROUND Cancer is one of the most serious threats to human health worldwide.Conventional treatments such as surgery and chemotherapy are associated with some drawbacks.In recent years,traditional Chinese medicine treatment has been increasingly advocated by patients and attracted attention from clinicians,and has become an indispensable part of the comprehensive treatment for gastric cancer.AIM To investigate the mechanism of Xiaojianzhong decoction(XJZ)in the treatment of gastric cancer(GC)by utilizing network pharmacology and experimental validation,so as to provide a theoretical basis for later experimental research.METHODS We analyzed the mechanism and targets of XJZ in the treatment of GC through network pharmacology and bioinformatics.Subsequently,we verified the impact of XJZ treatment on the proliferative ability of GC cells through CCK-8,apoptosis,cell cycle,and clone formation assays.Additionally,we performed Western blot analysis and real-time quantitative PCR to assess the protein and mRNA expression of the core proteins.RESULTS XJZ mainly regulates IL6,PTGS2,CCL2,MMP9,MMP2,HMOX1,and other target genes and pathways in cancer to treat GC.The inhibition of cell viability,the increase of apoptosis,the blockage of the cell cycle at the G0/G1 phase,and the inhibition of the ability of cell clone formation were observed in AGS and HGC-27 cells after XJZ treatment.In addition,XJZ induced a decrease in the mRNA expression of IL6,PTGS2,MMP9,MMP2,and CCL2,and an increase in the mRNA expression of HOMX1.XJZ significantly inhibited the expression of IL6,PTGS2,MMP9,MMP2,and CCL2 proteins and promoted the expression of the heme oxygenase-1 protein.CONCLUSION XJZ exerts therapeutic effects against GC through multiple components,multiple targets,and multiple pathways.Our findings provide a new idea and scientific basis for further research on the molecular mechanisms underlying the therapeutic effects of XJZ in the treatment of GC.
基金supported by Guangdong Bureau of Traditional Chinese Medicine (20211082)
文摘Objective To explore the influence of Linggui Zhugan Decoction(LGZGD) on high glucose induced podocyte autophagy.Methods LGZGD containing serum was prepared by intragastric administation of 4.2 g/kg(low dose), 8.4 g/kg(medium dose), and 12.6 g/kg(high dose) LGZGD into SD rats respectively. MPC5 and AB8/13 podocyte cells were treated with 60 mmol/L glucose to establish diabetic nephropathy podocyte model in vitro. Both podocytes were divided into control group, high glucose group, low dose LGZGD group, medium dose LGZGD group, and high dose LGZGD group, respectively. For the three LGZGD groups, before LGZGD intervention, podocytes were treated with 60 mmol/L glucose for 3 days. After treated with LGZGD containing serum, cells were collected to analyze cell migration using Transwell assay, proliferation using CCK8, apoptosis and cell cycle using flow cytometry, autophagosome formation using transmission electron microscopy, and expression levels of Beclin-1, Atg5, LC3II/I, and P62 proteins using Western blot.Results Compared with the control group, the proliferation and migration of MPC5 and AB8/13 cells in the high glucose group slightly decreased, whereas these parameters restored after intervention with low and medium concentrations of LGZGD, with the medium dose LGZGD having the better effect(P < 0.05). Flow cytometry showed that the medium dose LGZGD group had a significantly lower apoptosis rate(P < 0.05) and higher survival rate(P > 0.05) compared to the high dose LGZGD group. High glucose arrested podocytes in G1 phase, whereas LGZGD shifted podocytes from being predominant in G1 phase to G2 phase. High dose LGZGD significanly reduced high glucose-increased autophagosome formation in both podocytes(P < 0.05). Western blot analysis showed that Beclin-1, Atg5, LC3II/I, and P62 expressions were increased in MPC5 cells treated with high glucose and reversed after adminstration of low and medium doses of LGZGD(P < 0.05).Conclusion LGZGD reduced apoptosis and enhanced autophagy in high glucose treated podocytes via regulating Beclin-1/LC3II/I/Atg5 expression.
基金Supported by General Program of National Natural Science Foundation of China(31470075).
文摘[Objectives]To explore the effects of Shentong Zhuyu decoction combined with massage therapy in the treatment of exertional chronic lumbar muscle strain.[Methods]Sixty-four cases of exertional chronic lumbar muscle strain were randomly divided into two groups(32 cases each group).The patients in the control group only took celecoxib capsules,and those in the treatment group additionally took Shentong Zhuyu decoction combined with massage therapy.TCM syndrome score,lumbar function,hemorrheology index and clinical effect were compared between the two groups before and after treatment.[Results]After treatment,the TCM syndrome scores of lumbar distension/dull pain,tingling-like lumbago,adverse lateral turn,body weight loss,dark purple tongue,slow or astringent pulse,and Oswestry disability index(ODI)score in the treatment group were lower than those in the control group,and the levels of plasma viscosity,red blood cell aggregation index,platelet aggregation rate(PAG)and fibrinogen(Fib)were lower than those in the control group,showing statistical significance(P<0.05).The overall clinical effect distribution of the treatment group was better than that of the control group,and the difference was statistically significant(P<0.05).[Conclusions]Shentong Zhuyu decoction combined with massage therapy can effectively relieve the symptoms of patients with lumbago and improve the lumbar mobility function and hemorrheology,with obvious therapeutic effects in the treatment of exertional chronic lumbar muscle strain.
基金supported by the National Natural Science Foundation of China(81960851)Jiangxi Natural Science Foundation(20202BABL206132)Key Research Office of Traditional Chinese Medicine Syndrome Foundation of Jiangxi Administration of Traditional Chinese Medicine(8-4),and Science and Technology Innovation Team Development Program of Jiangxi University of Chinese Medicine(CXTD22016).
文摘Objective:To investigate the potential mechanism of Wendan decoction in obesity by screening target genes with promoter region methylation changes and constructing a multiple signaling pathways network based on promoter methylation.Methods:The methylation degree of Itgad,Col8a1,Adra2b,Jund,Rab2a,Wnt8b,Fzd9,B4galt7,Pik3cd,Creb1,Stard8,and Mmp1 in the abdominal adipose tissue of obese rats was determined using the Agena MassARRAY system.Western blot was performed to assess protein expression levels.Target genes were identified based on the methylation degree in the promoter region and protein expression.Enrichment analysis of signaling pathways was conducted to identify relevant target genes and obtain a multiple signaling pathway network associated with obesity.Core and terminal effector molecules in the pathway networks were selected as research targets for reverse transcription-polymerase chain reaction(RT-PCR)analysis.Results:Four genes(Adra2b,Creb1,Itgad,and Pik3cd)showed a degree of promoter methylation consistent with their respective protein expression levels.Among them,Adra2b,Creb1,and Pik3cd expression increased,while that of Itgad decreased.Enrichment analysis revealed that Creb1 and Pik3cd were involved in 6 signaling pathways related to obesity:tumor necrosis factor(TNF)signaling pathway,growth hormone synthesis/secretion and action,adenosine 5'-monophosphate-activated protein kinase(AMPK)signaling pathway,relaxin signaling pathway,cyclic nucleotide(cAMP)signaling pathway,and phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt)signaling pathway.Subsequently,a multiple signaling pathways network was constructed based on promoter methylation.Key molecules including protein kinase B(AKT),mechanistic target of rapamycin complex 1(mTORC1),and unc-51 like autophagy activating kinase 1(ULK1),as well as terminal effector molecules interleukin-1β(IL-1β),interleukin-6(IL-6),and chemokine(C-X-C motif)ligand 2(CXCL2)were selected as research targets.Wendan decoction decreased the expressions of AKT,mTORC1,IL-1β,IL-6,and CXCL2 while up-regulating ULK1 expression.Conclusion:The mechanism of Wendan decoction in preventing obesity involves the regulation of multiple signaling pathways through the control of Creb1 and Pik3cd gene promoter methylation.However,the associated multi-path gene regulation mechanism in preventing obesity is complex.Thus,further exploration is needed to elucidate the role of methylation changes in this mechanism.
基金2023 Young and Middle-aged University Teachers Basic Scientific Research Ability Improvement Project in Guangxi(2023KY0299)High-level Key Discipline Construction Project of Traditional Chinese Medicine of National Administration of Traditional Chinese Medicine(zyyzdxk-2023165)+3 种基金Talent Training Project of Guangxi International Zhuang Medicine Hospital—"Young Seedling Project"(2022001)Guangxi Traditional Chinese Medicine Multidisciplinary and Interdisciplinary Innovation Team Project(GZKJ2309)High-level Talent Cultivation Innovation Team Funding Project of Guangxi University of Chinese Medicine(2022A008)2023 Three-Year Action Plan Project for High-Level Talent Team Construction of Guangxi International Zhuang Medicine Hospital(GZCX20231203,GZCX20231202).
文摘[Objectives]To investigate the effect and mechanism of Dachengqi Decoction and separated decoction on incomplete intestinal obstruction in rats.[Methods]80 healthy SD rats were selected to establish incomplete intestinal obstruction model by silk ligation.The dosage was 20 mL/kg for 3 d,and the damage index of ileocecal mucosa was analyzed;the morphology of ileocecal mucosa was observed by HE staining;the serum levels of IL-1α,IL-1β,IL-6,IL-18,Ach,NO,ET,IL-1,TNF-αand ultra-micro Na+-K+-ATPase were detected by ELISA.[Results]Compared with the model group,the mucosal damage index of Dachengqi Decoction and each separated decoction group decreased significantly(P<0.05);compared with the normal group and sham operation group,the serum level of IL-1,IL-6,TNF-αand other factors in the model group increased significantly(P<0.05);compared with the model group,the serum IL-1,IL-6 and TNF-αsecretion levels of rats in Dachengqi Decoction group and separated decoction group decreased(P<0.01).[Conclusions]Dachengqi Decoction and each separated decoction can effectively improve intestinal tissue pathological damage in the incomplete intestinal obstruction model rats,and reduce the inflammatory reaction in the rat body.
基金This research is financed by the grant from National Social Science Fund(No.18ZDA175).
文摘During the late Qing dynasty(1840 A.D.-1912 A.D.),a large quantity of Western medicines entered China,which continuously impacted the traditional Chinese medicine(TCM)market and revealed the shortcomings of Chinese medicines.Some personages in the TCM community followed the trend of learning from the West,and attempted to reform TCM,with the improvement on decoction becoming an important aspect of this effort.Through debates and trials,the improvement on decoction underwent three stages of conceptual evolution:“taking Chinese medicines as the foundation and referring to the dosage forms of Western medicines”,“introducing Western techniques to serve the preparation of decoctions”and“integrating the theories of TCM and Western medicine to improve decoctions”.The study highlights the effective complementarity between modern TCM and Western medicine in the field of pharmacy,and provides valuable experience and support for the reevaluation of the value of TCM in contemporary society.
基金supported by the National Natural Science Foundation of China(81874421)the Innovation Team and Talents Cultivation Program of the National Administration of Traditional Chinese Medicine(ZYYCXTD-C-202006).
文摘Objective:To uncover the underlying mechanisms of action of the Yinlai decoction on high-calorie dietinduced pneumonia through proteomics analysis.Methods:Based on the Gene Expression Omnibus(GEO)database,lung tissue samples from normal and high-fat diet(HFD)fed mice in the GSE16377 dataset were selected as test cohorts to identify differentially expressed genes and conduct bioinformatics analyses.In the animal experiments,mice were randomly divided into the control(N),high-calorie diet pneumonia(M),and Yinlai decoction treatment(Y)groups.Mice in the M group received high-calorie feed and a 0.5 mg/mL lipopolysaccharide solution spray for 30 min for 3 d.The mice in the Y group were intragastrically administered 2 mL/10 g Yinlai decoction twice daily for 3 d.Pathological evaluation of the lung tissue was performed.Differentially expressed proteins(DEPs)in the lung tissue were identified using quantitative proteomics and bioinformatics analyses.The drug-target relationships between Yinlai decoction and core DEPs in the lung tissue were verified using AutoDock Vina and Molecular Graphics Laboratory(MGL)Tools.DEPs were verified by western blot.Results:GEO data mining showed that an HFD altered oxidative phosphorylation in mouse lung tissue.The Yinlai decoction alleviated pathological damage to lung tissue and pneumonia in mice that were fed a high-calorie diet.A total of 47 DEPs were identified between the Y and M groups.Enrichment analysis revealed their association with energy metabolism pathways such as the tricarboxylic acid cycle(TCA)and oxidative phosphorylation.The protein-protein interaction network revealed that Atp5a1,Pdha1,and Sdha were the target proteins mediating the therapeutic effects of Yinlai decoction.Molecular docking results suggested that the mechanism of the therapeutic effect of Yinlai decoction involves the binding of brassinolide,praeruptorin B,chrysoeriol,and other components in Yinlai decoction to Atp5a1.Conclusion:The Yinlai decoction alleviated lung tissue damage and pneumonia in mice that were fed a high-calorie diet by regulating the TCA and oxidative phosphorylation.Our study highlights the importance of a healthy diet for patients with pneumonia and provides a scientific basis for the prevention and treatment of pneumonia through dietary adjustments.
基金National Natural Science Foundation Project of China(No.81904230,82205155)Capital Health Development Research Project(No.2018-2-4162)。
文摘Objective:To systematically evaluate the long-term efficacy of Bushen Huoxue Decoction combined with vertebroplasty(PVP or PKP)in the treatment of osteoporotic vertebral compression fractures(OVCF),in order to provide evidence-based reference for clinical application.Methods:To ensure the novelty of research data,a computer search was conducted between 2017 and February 2023 to publicly publish all randomized controlled studies and clinical trials at home and abroad on the treatment of OVCF with Bushen Huoxue Decoction combined with vertebroplasty published in CNKI,Wanfang,Vip,PubMed,CBM,and Cochrane libraries.Two researchers independently conducted literature screening and data extraction,evaluated the quality of randomized controlled trials included one by one according to the Cochrane collaboration network standards,and conducted a meta statistical analysis using RevMan5.3 for studies that met the inclusion criteria.Results:A total of 684 patients were included in 7 randomized controlled trials,including 342 patients in the observation group and 342 patients in the control group,with a ratio of 1:1;The meta-analysis results showed that in the observation group,the overall effective rate[RR=1.30,95%CI(1.14,1.47),P<0.001],visual analog pain(VAS)score[SMD=1.19,95%CI(0.77,1.61),P<0.0001],bone mineral density score[SMD=1.09,95%CI(0.15,2.04),P=0.02],COQOL score[SMD=0.99,95%CI(0.68,1.30),P<0.00001],OPG score[SMD=0.48,95%CI(0.18,0.77),P=0.002]The RANKL score[SMD=1.33,95%CI(1.00,1.65),P<0.0001]was significantly superior to the control group,with statistically significant differences.There was no significant difference in the Oswestry Disability Index(ODI)score[SMD=0.27,95%CI(-0.03,0.57),P=0.08],Cobb score[SMD=1.52,95%CI(-1.05,4.09),P=0.25],and vertebral height score[SMD=0.43,95%CI(-0.14,1.01),P=0.14].Conclusion:The results show that Bushen Huoxue Decoction combined with vertebroplasty has significant advantages in improving bone mineral density and alleviating pain in patients after OVCF,which is significantly superior to using OVCF alone.
基金Guangxi Natural Science Foundation(No.2020GXNSFAA297158)The Fifth Batch of National Clinical Excellent Talent Training Projects[Guozhong Pharmaceutical Education(2022)No.1]+1 种基金Guangxi Youth Qihuang Scholar Training Program[Guizhong Medical Science and Education Development(2022)No.13]Guangxi Graduate Education Innovation Program Project(No.YCSW2022340)。
文摘Objective: To investigate the differential expression of miRNA and related biological functions and signaling pathways after the intervention of the THP-1-derived foam cell model with the drug-containing serum of Yimaijiangzhi Decoction. Methods: The experiment was divided into macrophage group, foam cell model group and Yimaijiangzhi drug-containing serum group. THP-1 cells were induced into macrophages by Fopol ester, and induced differentiated macrophages were given ox-LDL to establish foam cell model, and Yimaijiangzhi decoction rat serum was used to intervene the foam cells. Total RNA was extracted from cells in each group for miRNA sequencing, differential expression of miRNA was screened, and relevant target genes were predicted for GO analysis and KEGG analysis, protein interaction network and miRNA-target gene interaction network were established, and RT-qPCR was used to verify the possible signaling pathways for improving atherosclerosis. Result: The difference miRNA between blank group and model group was hsa-miR-302c-3p, hsa-miR-302d-3p, hsa- mir-30d-3p, hsa-mir-3189-3p, hsa-mir-374b-5p, hsa-mir-423-5p, hsa-mir-423-5p, and hsa- mir-4781-3p, hsa-mir-663a;The miRNAs of model group and Yimaijiangzhi drug-containing serum group were hsa-mir-3150a-3p, hsa-mir-7704, hsa-mir-887-3p, hsa-mir-150-5p, hsa- mir-423-5p, hsa-mir-374c-3p, hsa-mir-374c-3p, hsa-mir-374b-5p;The difference of miRNAs prediction target genes between model group and Yimaijiangzhi drug-containing serum group showed that the miRNA prediction target genes were mainly enriched in MAPK signaling pathway, ErbB signaling pathway, Hippo signaling pathway, Wnt signaling pathway and other signaling pathways. SCN1A, PRKACA, MECP2, EIF4E, SRSF1, MBNL1, PRKCA, PPARGC1A may be the potential key targets for the effect of the drug-containing serum of Yimaijiangzhi Decoction on THP-1-derived foam cells. Conclusion: hsa-mir-374c-3p, hsa- mir-423-5p, and hsa-mir-374b-5p are important miRNAs that the drug-containing serum of Yimaijiangzhi Decoction acts on foam cells. The significantly differentially expressed mirnas and significantly enriched related signaling pathways may provide new ideas for the diagnosis and treatment of atherosclerosis.
基金supported by grants from the Special Project for Transformation of Scientific and Technological Achievements in Qinghai Province(No.2021-SF-150)the National Natural Science Foundation of China(No.82173929).
文摘Background:Sanhua decoction has significant effects in the treatment of stroke.The study of the Sanhua decoction material benchmark was carried out to analyze the value transfer relationship between the Chinese herbal pieces and the substance benchmark.Methods:Network pharmacology was employed to investigate the potential active components and molecular mechanisms of Sanhua decoction in the treatment of stroke.15 batches of Sanhua decoction lyophilized powder were prepared using traditional formulas and subjected to high-performance liquid chromatography analysis to generate fingerprints of the Sanhua decoction substance benchmarks.Then,a multi-component quantitative analysis method was established,allowing for the simultaneous determination of ten components,to study the transfer of quantity values between pieces and substance benchmarks.Results:60 active ingredients were screened from Sanhua decoction by network pharmacology,of which gallic acid,magnolol honokiol,physcion,and aloe-emodin may have a greater effect than other active components.63 key targets and 134 pathways were predicted as the potential mechanism of Sanhua decoction in treating stroke.The fingerprint similarity of the Sanhua decoction substance benchmarks was found to be good among the 15 batches,confirming the 19 common peaks.The content of the 10 components was basically consistent.The components’transfer rates were within 30%of their respective means.Conclusions:This study provided a comprehensive and reliable strategy for the quality evaluation of Sanhua decoction substance benchmarks and held significant importance in improving its application value.