BACKGROUND Hepatocellular carcinoma(HCC)is one of the most prevalent cancers in human populations worldwide.Huanglian decoction is one of the most important Chinese medicine formulas,with the potential to treat cancer...BACKGROUND Hepatocellular carcinoma(HCC)is one of the most prevalent cancers in human populations worldwide.Huanglian decoction is one of the most important Chinese medicine formulas,with the potential to treat cancer.AIM To investigate the role and mechanism of Huanglian decoction on HCC cells.METHODS To identify differentially expressed genes(DEGs),we downloaded gene expression profile data from The Cancer Genome Atlas Liver Hepatocellular Carcinoma and Gene Expression Omnibus(GSE45436)databases.We obtained phytochemicals of the four herbs of Huanglian decoction from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform.We also established a regulatory network of DEGs and drug target genes and subsequently analyzed key genes using bioinformatics approaches.Furthermore,we conducted in vitro experiments to explore the effect of Huanglian decoction and to verify the predictions.In particular,the CCNB1 gene was knocked down to verify the primary target of this decoction.Through the identification of the expression levels of key proteins,we determined the primary mechanism of Huanglian decoction in HCC.RESULTS Based on the results of the network pharmacological analysis,we revealed 5 bioactive compounds in Huanglian decoction that act on HCC.In addition,a protein-protein interaction network analysis of the target genes of these five compounds as well as expression and prognosis analyses were performed in tumors.CCNB1 was confirmed to be the primary gene that may be highly expressed in tumors and was significantly associated with a worse prognosis.We also noted that CCNB1 may serve as an independent prognostic indicator in HCC.Moreover,in vitro experiments demonstrated that Huanglian decoction significantly inhibited the growth,migration,and invasiveness of HCC cells and induced cell apoptosis and G2/M phase arrest.Further analysis showed that the decoction may inhibit the growth of HCC cells by downregulating the CCNB1 expression level.After Huanglian decoction treatment,the expression levels of Bax,caspase 3,caspase 9,p21 and p53 in HCC cells were increased,while the expression of CDK1 and CCNB1 was significantly decreased.The p53 signaling pathway was also found to play an important role in this process.CONCLUSION Huanglian decoction has a significant inhibitory effect on HCC cells.CCNB1 is a potential therapeutic target in HCC.Further analysis showed that Huanglian decoction can inhibit HCC cell growth by downregulating the expression of CCNB1 to activate the p53 signaling pathway.展开更多
[Objectives]To study the effect of Huanglian Jiedu Decoction on the behavior of zebrafish with Alzheimer's disease caused by AlCl 3.[Methods]Each portion of Huanglian Jiedu Decoction was prepared according to the ...[Objectives]To study the effect of Huanglian Jiedu Decoction on the behavior of zebrafish with Alzheimer's disease caused by AlCl 3.[Methods]Each portion of Huanglian Jiedu Decoction was prepared according to the proportion of Coptis chinensis∶Phellodendron chinense Rupr.∶Scutellaria baicalensis Georgi∶Gardenia jasminoides Ellis=63 g∶42 g∶42 g∶63 g.After that,each portion of Huanglian Jiedu Decoction was soaked in 6.3 L water for 30 min and boiled twice at 100℃.The extracts were combined twice and filtered,then concentrated to 308 g/L and put into refrigerator for later use.Before training,zebrafishes were put into T-maze to adapt for 2 d,and then behavioral training was carried out for 7 d.After video recording,the behavior of zebrafish was analyzed by Smart 3.0,and qualified zebrafishes were selected for follow-up experiments.Then 60 successfully trained zebrafishes were randomly divided into control group,model group,positive group,low-dose group,medium-dose group and high-dose group of Huanglian Jiedu Decoction.Except for the control group,all the other groups were exposed to 100μg/L AlCl 3 for 7 d.After that,video was recorded,and behavioral analysis was carried out with behavioral record and analysis software Smart 3.0.And then the zebrafishes in the other four groups except the model group were treated with Huperzine A(4μg/L)and Huanglian Jiedu Decoction(154,308,616 mg/L)for 6 d,respectively.After that,it was recorded and the behavior of each group was analyzed.[Results]There was a significant difference in the time spent in the left area and the percentage of time in the left area between the control group and the model group(P<0.001).The time spent in the left area and the percentage of time in the left area in the model group and positive group,low,medium and high dose groups of Huanglian Jiedu Decoction decreased significantly(P<0.05,P<0.01,P<0.001).The swimming distance in the left area and the percentage of swimming distance in the left area in the model group were significantly higher than those in the control group(P<0.001).There was a significant difference in swimming distance between model group and positive group,low,medium and high dose groups of Huanglian Jiedu Decoction(P<0.01,P<0.001).In the percentage of swimming distance in the left area,there was a significant difference between the model group and the low and high dose groups of Huanglian Jiedu Decoction(P<0.01,P<0.001).[Conclusions]Huanglian Jiedu Decoction can improve the behavior of zebrafish with Alzheimer's disease.展开更多
Huanglian Jiedu decoction (HLJDD) has been shown to improve cerebral blood flow, and reduce lipid peroxidation damage to the brain and its energy metabolism. The present study was designed to observe the cerebroprot...Huanglian Jiedu decoction (HLJDD) has been shown to improve cerebral blood flow, and reduce lipid peroxidation damage to the brain and its energy metabolism. The present study was designed to observe the cerebroprotective effect of HL.JDD on an Alzheimer's disease rodent model, presenilin-1/amyloid protein precursor double transgenic mice. HLJDD reduced serum interleukin-6 and interleukin-113 levels, decreased [3-amyloid precursor protein gene and senile plaque expression, resisted oxidation, and reduced free radical-induced injury, thereby improving the learning and memory of these mice. Moreover, HLJDD at 433 mg/kg per day exhibited better effects compared with that at 865 or 216 mg/kg per day, and donepezil hydrochloride at 30 mg/kg per day. Thus, these results suggest that HLJDD may have protective effects against Alzheimer's disease.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
Objective:To explore the common mechanism of Huanglian Jiedu Decoction in treating coronary heart disease and type 2 diabetes by network pharmacology.Methods:All chemical components and targets of the four drugs in Hu...Objective:To explore the common mechanism of Huanglian Jiedu Decoction in treating coronary heart disease and type 2 diabetes by network pharmacology.Methods:All chemical components and targets of the four drugs in Huanglian Jiedu Decoction were retrieved through TCMSP,and the genes were standardized through Uniprot database.Acquire disease targets related to coronary heart disease and diabetes in OMIM and GeneCards databases.The network diagram of"drug-component-target-disease"is constructed by using the software of cytopscape 3.7.2,the PPI network diagram of protein interaction is constructed by using STRING database,and the network diagram of"drug-disease"core target is constructed by using the software of cytopscape 3.7.2.DAVID's online database platform was used to analyze GO biological process and KEGG pathway enrichment of common targets of Huanglian Jiedu Decoction in treating coronary heart disease and type 2 diabetes.Results:103 active ingredients of Huanglian Jiedu Decoction were retrieved,including 140 acting targets,5342 coronary heart disease targets,114 diabetes targets,and 14 common intersection targets of drugs and diseases,involving AR,PPARG,TNF,IL6,CCL2,VEGFA,PON1,etc.The GO biological process analysis results in 98 biological processes,10 cell components and 10 molecular functions.Among them are positive regulation of gene expression,positive regulation of nitric oxide biosynthesis process,Extracellular space,cytokine activity,steroid hormone receptor activity and other biological processes;The enrichment analysis of KEGG pathway yielded 20 signal pathways(P≤0.05).It mainly involves Malaria,cancer in cancer,HIF-1 signaling pathway,TNF signaling pathway,NOD-like receptor signaling pathway,PI3K-Akt signaling pathway,etc.Conclusion:Huanglian Jiedu Decoction"treats different diseases at the same time"coronary heart disease and type 2 diabetes have the characteristics of multiple components,multiple targets and multiple pathways,which provide theoretical basis for Huanglian Jiedu Decoction to treat coronary heart disease and type 2 diabetes in clinic,but the key targets and pathways of Huanglian Jiedu Decoction to treat diseases still need further experimental verification.展开更多
Objective:To explore the active ingredients of Huanglian Jiedu Decoction(HLJD)for the treatment of COVID-19 and to further verify the combination mode.Methods:The TCMSP database was used to search for HLJD active ingr...Objective:To explore the active ingredients of Huanglian Jiedu Decoction(HLJD)for the treatment of COVID-19 and to further verify the combination mode.Methods:The TCMSP database was used to search for HLJD active ingredients and targets.COVID-19 targets were collected from GeneCards,DisGeNET and OMIM databases.Material-active-ingredients-targets(gene)network and targets protein-protein interaction network were constructed using Cytoscape 3.8.0 and the STRING database.GO functional enrichment analysis and KEGG pathway enrichment analysis of core targets were performed using R software.Cytoscape 3.8.0 was used to build“compound-targets-pathways”to predict HLJD mechanisms,and active ingredients were used as ligands to molecularly dock with SARS-CoV-23CL hydrolase,Spike glycoprotein and ACE2.The binding energy was calculated by molecular dynamics simulations and molecular mechanics Poisson-Boltzmann surface area method,and intermolecular interactions and the contribution of each residue to the binding free energy were analyzed.Results:Four medicinal materials,66 compounds and 219 targets were identified.It is found that the Protein-Protein Interaction core network contained 35 HLJD key targets proteins for COVID-19 treatment.705 GO functional enrichment entries(P<0.05)were produced;while KEGG pathway enrichment analysis identified 142 pathways(P<0.05)involving the Tumor Necrosis Factor signaling pathway and Interleukin-17 signaling pathway,etc.The binding energies of Kihadanin A,Palmidin A,Obacunone and Hispidone are much smaller than those of the currently reported clinical drugs with anti-SARS-CoV-2 drugs.The results of the binding energy indicate that van der Waals force is the main driving force for enzyme-substrate combination,whereas the electrostatic interaction and non-polar solvents contribute less.Conclusion:The“multi-component-multi-targets-multi-pathway”synergy of HLJD,which binds to SARSCoV-23CL hydrolase,Spike glycoprotein and ACE2,can act on targets Heat Shock Protein 90 Alpha Family Class A Member 1,Adrenoceptor Beta 2,Checkpoint Kinase 1,Peroxisome Proliferator-Activated Receptor Gamma and Mitogen-activated protein kinase 14 to regulate multiple signal pathways,and it may have a therapeutic effect on COVID-19.展开更多
Huanglian Wendan decoction(HLWDD) has been used for the treatment of symptom of "Re", one of major causes in diabetes and metabolic disorders, according to the theory of traditional Chinese medicine. The pre...Huanglian Wendan decoction(HLWDD) has been used for the treatment of symptom of "Re", one of major causes in diabetes and metabolic disorders, according to the theory of traditional Chinese medicine. The present study aimed at investigating the cerebral protective effects of HLWDD on diabetic encephalopathy(DE), one of the major diabetic complications. The effects of HLWDD and metformin were analyzed in the streptozocin(STZ) + high-glucose-fat(HGF) diet-induced DE rats by gastric intubation. In the present study, the effects of HLWDD on cognition deficits were investigated after 30-day intervention at two daily dose levels(3 and 6 g·kg^(-1)). To explore the potential mechanisms underlying the effects of HLWDD, we detected the alterations of neuronal damages, inflammatory cytokines, and impaired insulin signaling pathway in hippocampus of the DE rats. Based on our results from the present study, we concluded that the protective effects of HLWDD against the cognitive deficits and neuronal damages through inhibiting the release of inflammatory cytokines and repairing insulin signaling pathway in hippocampus of the DE rats.展开更多
Objective To develop a sensitive and rapid liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) method for the simultaneous determination of wogonin, coptisine, berberine, palmatine,...Objective To develop a sensitive and rapid liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) method for the simultaneous determination of wogonin, coptisine, berberine, palmatine, jatrorrhizine, phellodendrine, magnoflorine, and wogonoside in rat plasma and to evaluate the pharmacokinetic characteristics of Huanglian Jiedu Decoction (HJD). Methods LC separation was performed on an Acquity HSS T3 column (100 mm × 2.1 mm, 1.8 μm) using gradient elution with the mobile phase consisting of acetonitrile and 0.1% formic acid water. The detection was accomplished by using positive electrospray ionization in multiple-reaction monitoring mode. Plasma samples were pretreated by protein precipitation. Results The method showed a good linearity over a wide concentration range (r^2 〉 0.99). The lower limits of quantification were 0.20 ng/mL for coptisine and phellodendrine, 0.48 ng/mL for berberine, 0.10 ng/mL for jatrorrhizine, 0.32 ng/mL for magnoflorine, 0.30 ng/mL for palmatine, and 4.80 ng/mL for wogonin and wogonoside, respectively. The intra- and inter-day precision of the analytes was less than 12.11%, while the accuracy was between -14.46% and 4.86%. The mean recovery of all the analytes ranged from 93.10% to 110.91%. Conclusion This validated method offers thee advantages of high sensitivity. It is successfully applied to evaluating the pharmacokinetic properties of HJD.展开更多
Objective: To investigate the effects of Huanglian Jiedu Decoction (黄连解毒汤, HLJDD) on glucose transporter 4 (GLUT4) protein expressions in insulin-resistant murine target tissues. Methods: The experimental m...Objective: To investigate the effects of Huanglian Jiedu Decoction (黄连解毒汤, HLJDD) on glucose transporter 4 (GLUT4) protein expressions in insulin-resistant murine target tissues. Methods: The experimental male Wistar rats were established into insulin resistant models by injecting streptozotocin (STZ 30 mg/kg) via caudal vein and feeding them with high fat high caloric diet, and randomly divided into the model group, the aspirin group and the HLJDD group. Besides, a normal group was set up for control. Changes of body weight (BW), levels of serum fasting blood glucose (FBG), serum fasting insulin (FINS) and oral glucose tolerance test (OGTT) were routinely determined. The expression of GLUT4 protein in adipose and skeletal muscle tissues before and after insulin stimulation was determined with Western blot. Results: In the HLJDD group after treatment, BW and FBG got decreased, OGTT improved, and the expression and translocation of GLUT4 protein elevated obviously, either before or after insulin stimulation, as compared with those in the model group, showing significant differences respectively. Conclusion: The mechanism of improving insulin resistance by HLJDD is probably associated with its effect in elevating GLUT4 protein expression and translocation in adipose and skeletal muscle tissues of insulin resistant rats.展开更多
Objective:To evaluate the effect of heat-clearing and detoxifying method on the macrophages polarization in patients with acute myocardial infarction with heat toxin syndrome after intervention.Methods:Sixty patients ...Objective:To evaluate the effect of heat-clearing and detoxifying method on the macrophages polarization in patients with acute myocardial infarction with heat toxin syndrome after intervention.Methods:Sixty patients with acute myocardial infarction and undergoing percutaneous coronary intervention with heat toxin syndrome were randomly divided into a control group and a test group with 30 cases each.The control group was given conventional treatment,and the test group was given Huanglian Jiedu Decoction,the representative of the method of clearing heat and detoxification,orally on the basis of the control group.The intervention time of both groups was 2 weeks.Comparing The Seattle Angina Pectoris Scale(SAQ)before and after treatment,creatine kinase(CK),creatine kinase MB isoenzyme(CKMB),high-sensitivity troponin I(hs-TnI),and Lipoprotein-associated phospholipaseA2(LPPLA_2)),the phenotype ratio of M1 and M2 macrophages,and observe the adverse reactions.Results:After treatment,the SAQ scores of the two groups of patients were improved,and the levels of CK,CK-MB,hs-TnI,and LP-PLA_2 decreased significantly.The scores of AS,AF,TS,and DP in the SAQ of the test group were all higher than those of the control group,and the hs-TnI and LP-PLA_2 were better than those of the control Group(P<0.05 or P<0.01).After treatment,the proportion of M1 type macrophages in the two groups of patients'macrophages decreased significantly(P<0.05 or P<0.01),the ratio of M2 type macrophages increased(P<0.05),and the M1/M2 ratio decreased.The ratio of M1/M2 in the test group of the control group was significantly lower than that of the control group(P<0.01).There were no obvious adverse reactions in both groups.Conclusions:The method of clearing heat and detoxifying has a definite effect on patients with acute myocardial infarction of heat toxin syndrome after interventional operation.It can reduce myocardial damage,improve myocardial function,and reduce inflammation.And it is safe for clinical treatment without any increasing risk of bleeding or other risk of cardiovascular events.展开更多
Background Sepsis is a complex pathophysiologic process, which is the leading cause of death in the world. Many studies have revealed that Chinese medicine has shown tremendous advantages on the treatment of sepsis. O...Background Sepsis is a complex pathophysiologic process, which is the leading cause of death in the world. Many studies have revealed that Chinese medicine has shown tremendous advantages on the treatment of sepsis. Our study aims to explore the effect of Huanglian jiedu decoction and Jiawei huanglian jiedu decoction on organ function in septic rats. Methods SD rats were randomly divided into 7 groups, sham-group, cecal ligation and puncture group (CLP, 18h/72h), Jiawei huanglian jiedu decoction group (JW, 18h/72h), Huanglian jiedu decoc-tion group (W, 18h/72h). Except the Sham group, the rats in other groups received cecal ligation and puncture method to induce sepsis. CLP groups were intragastric administration with normal saline after CLP. Huanglian jiedu decoction and Jiawei huanglian jiedu decoction groups were intragastric administration with Huanglian jie-du decoction and Jiawei huanglian jiedu decoction in the same time points. Glutamic-pyruvic transaminase (ALT), glutamic oxalacetic transaminase (AST), total bilirubin (TBIL), creatinine(Cr), urea, creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH) were detected by biochemical analyzer. Brain natriuretic peptide (BNP), surfactant protein A (SP-A), chemotactic factor for monocyte-1 (MCP-1), D-lactic acid (D-LAC), complement 5a, mobility group box-1 protein B 1 (HMGB-1), interleukin 6 (IL-6) were analyzed by enzyme-linked immunosor-bent assay (ELISA). Total lung capacity (TLC) and function residual capacity (FRC) were measured by buxco re-search system. The wet to dry weight ratio (W/D) was tested. Moreover, changes in tissue pathology were evaluat-ed using hematoxylin and eosin (H&E) staining and electron microscope. Results The level of AST/ALT in se-rum was decreased after treatment with Huanglian jiedu decoction and Jiawei huanglian jiedu decoction. More-over, the level of TLC and FRC was significantly increased, and the level of SP-A, W/D was significantly de-creased. In addition, the level of CK-MB, IL-6, HMGB-1 and MCP-1 in serum was decreased. Inflammation fac-tors were positively correlated with lung function, and the cardiac function was positively correlated with the or-gan function, the differences were statistically significant. In addition, the histological alterations of myocardium, lung and intestine were attenuated after treatment with Huanglian jiedu decoction and Jiawei huanglian jiedu de-coction. Conclusion Huanglian jiedu decoction and Jiawei huanglian jiedu decoction can inhibit the inflamma-tory infiltration of septic rats and improve organ function.展开更多
Background Huanglian Jiedu Decoction(HJD) is a typical traditional Chinese medicine which exhibits diverse curative effects against different kinds of diseases because of its multi-components and multi-targets. It has...Background Huanglian Jiedu Decoction(HJD) is a typical traditional Chinese medicine which exhibits diverse curative effects against different kinds of diseases because of its multi-components and multi-targets. It has been widely used for the treatment of sepsis. However, the underlying molecular mechanism is still unclear.Methods Network pharmacology was applied to analyze the potential active ingredients and molecular mechanism of HJD in the treatment of sepsis.Results As a result, we totally found 102 active ingredients and 221 corresponding targets. Among them, 117 were hit by the 1 837 targets associated with sepsis. Our further analysis demonstrated 57 drug and disease intersection targets. Based on Gene Ontology(GO) enrichment analysis, 2176 biological process terms, 84 molecular function terms and 28 cellular component terms were acquired. By performing Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis, we acquired the dominating signaling pathways associated with sepsis. By constructing protein-protein interaction network of common targets, 11 hub genes were identified.Conclusions Taken together, our results indicated that HJD may protect against sepsis via a mechanism involving multiple targets and pathways.展开更多
文摘BACKGROUND Hepatocellular carcinoma(HCC)is one of the most prevalent cancers in human populations worldwide.Huanglian decoction is one of the most important Chinese medicine formulas,with the potential to treat cancer.AIM To investigate the role and mechanism of Huanglian decoction on HCC cells.METHODS To identify differentially expressed genes(DEGs),we downloaded gene expression profile data from The Cancer Genome Atlas Liver Hepatocellular Carcinoma and Gene Expression Omnibus(GSE45436)databases.We obtained phytochemicals of the four herbs of Huanglian decoction from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform.We also established a regulatory network of DEGs and drug target genes and subsequently analyzed key genes using bioinformatics approaches.Furthermore,we conducted in vitro experiments to explore the effect of Huanglian decoction and to verify the predictions.In particular,the CCNB1 gene was knocked down to verify the primary target of this decoction.Through the identification of the expression levels of key proteins,we determined the primary mechanism of Huanglian decoction in HCC.RESULTS Based on the results of the network pharmacological analysis,we revealed 5 bioactive compounds in Huanglian decoction that act on HCC.In addition,a protein-protein interaction network analysis of the target genes of these five compounds as well as expression and prognosis analyses were performed in tumors.CCNB1 was confirmed to be the primary gene that may be highly expressed in tumors and was significantly associated with a worse prognosis.We also noted that CCNB1 may serve as an independent prognostic indicator in HCC.Moreover,in vitro experiments demonstrated that Huanglian decoction significantly inhibited the growth,migration,and invasiveness of HCC cells and induced cell apoptosis and G2/M phase arrest.Further analysis showed that the decoction may inhibit the growth of HCC cells by downregulating the CCNB1 expression level.After Huanglian decoction treatment,the expression levels of Bax,caspase 3,caspase 9,p21 and p53 in HCC cells were increased,while the expression of CDK1 and CCNB1 was significantly decreased.The p53 signaling pathway was also found to play an important role in this process.CONCLUSION Huanglian decoction has a significant inhibitory effect on HCC cells.CCNB1 is a potential therapeutic target in HCC.Further analysis showed that Huanglian decoction can inhibit HCC cell growth by downregulating the expression of CCNB1 to activate the p53 signaling pathway.
基金Supported by National Natural Science Foundation of China(82160832)Natural Science Foundation of Guangxi Zhuang Autonomous Region(2017GXNSFAA198255,2018GXNSFBA138028)+2 种基金the Open Project Program of Guangxi Key Laboratory of Brain and Cognitive Neuroscience,Guilin Medical University(GKLBCN-202206-02,GKLBCN-202206-05)2022 Annual Scientific Research Project of Guangdong Provincial Administration of Traditional Chinese Medicine(20222138)the Fourth Training Plan for Thousands of Young and Mid-aged Mainstay Teachers in Guangxi Colleges and Universities,and the Innovation and Entrepreneurship Training Program for College Students in Guilin Medical University in 2022(202210601214).
文摘[Objectives]To study the effect of Huanglian Jiedu Decoction on the behavior of zebrafish with Alzheimer's disease caused by AlCl 3.[Methods]Each portion of Huanglian Jiedu Decoction was prepared according to the proportion of Coptis chinensis∶Phellodendron chinense Rupr.∶Scutellaria baicalensis Georgi∶Gardenia jasminoides Ellis=63 g∶42 g∶42 g∶63 g.After that,each portion of Huanglian Jiedu Decoction was soaked in 6.3 L water for 30 min and boiled twice at 100℃.The extracts were combined twice and filtered,then concentrated to 308 g/L and put into refrigerator for later use.Before training,zebrafishes were put into T-maze to adapt for 2 d,and then behavioral training was carried out for 7 d.After video recording,the behavior of zebrafish was analyzed by Smart 3.0,and qualified zebrafishes were selected for follow-up experiments.Then 60 successfully trained zebrafishes were randomly divided into control group,model group,positive group,low-dose group,medium-dose group and high-dose group of Huanglian Jiedu Decoction.Except for the control group,all the other groups were exposed to 100μg/L AlCl 3 for 7 d.After that,video was recorded,and behavioral analysis was carried out with behavioral record and analysis software Smart 3.0.And then the zebrafishes in the other four groups except the model group were treated with Huperzine A(4μg/L)and Huanglian Jiedu Decoction(154,308,616 mg/L)for 6 d,respectively.After that,it was recorded and the behavior of each group was analyzed.[Results]There was a significant difference in the time spent in the left area and the percentage of time in the left area between the control group and the model group(P<0.001).The time spent in the left area and the percentage of time in the left area in the model group and positive group,low,medium and high dose groups of Huanglian Jiedu Decoction decreased significantly(P<0.05,P<0.01,P<0.001).The swimming distance in the left area and the percentage of swimming distance in the left area in the model group were significantly higher than those in the control group(P<0.001).There was a significant difference in swimming distance between model group and positive group,low,medium and high dose groups of Huanglian Jiedu Decoction(P<0.01,P<0.001).In the percentage of swimming distance in the left area,there was a significant difference between the model group and the low and high dose groups of Huanglian Jiedu Decoction(P<0.01,P<0.001).[Conclusions]Huanglian Jiedu Decoction can improve the behavior of zebrafish with Alzheimer's disease.
基金the Natural Science Foundation of Hubei Province, No. 2007ABA060
文摘Huanglian Jiedu decoction (HLJDD) has been shown to improve cerebral blood flow, and reduce lipid peroxidation damage to the brain and its energy metabolism. The present study was designed to observe the cerebroprotective effect of HL.JDD on an Alzheimer's disease rodent model, presenilin-1/amyloid protein precursor double transgenic mice. HLJDD reduced serum interleukin-6 and interleukin-113 levels, decreased [3-amyloid precursor protein gene and senile plaque expression, resisted oxidation, and reduced free radical-induced injury, thereby improving the learning and memory of these mice. Moreover, HLJDD at 433 mg/kg per day exhibited better effects compared with that at 865 or 216 mg/kg per day, and donepezil hydrochloride at 30 mg/kg per day. Thus, these results suggest that HLJDD may have protective effects against Alzheimer's disease.
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.
基金National Major Specialized Science and Technology Project for New Drugs Development(No.2017ZX09301003)。
文摘Objective:To explore the common mechanism of Huanglian Jiedu Decoction in treating coronary heart disease and type 2 diabetes by network pharmacology.Methods:All chemical components and targets of the four drugs in Huanglian Jiedu Decoction were retrieved through TCMSP,and the genes were standardized through Uniprot database.Acquire disease targets related to coronary heart disease and diabetes in OMIM and GeneCards databases.The network diagram of"drug-component-target-disease"is constructed by using the software of cytopscape 3.7.2,the PPI network diagram of protein interaction is constructed by using STRING database,and the network diagram of"drug-disease"core target is constructed by using the software of cytopscape 3.7.2.DAVID's online database platform was used to analyze GO biological process and KEGG pathway enrichment of common targets of Huanglian Jiedu Decoction in treating coronary heart disease and type 2 diabetes.Results:103 active ingredients of Huanglian Jiedu Decoction were retrieved,including 140 acting targets,5342 coronary heart disease targets,114 diabetes targets,and 14 common intersection targets of drugs and diseases,involving AR,PPARG,TNF,IL6,CCL2,VEGFA,PON1,etc.The GO biological process analysis results in 98 biological processes,10 cell components and 10 molecular functions.Among them are positive regulation of gene expression,positive regulation of nitric oxide biosynthesis process,Extracellular space,cytokine activity,steroid hormone receptor activity and other biological processes;The enrichment analysis of KEGG pathway yielded 20 signal pathways(P≤0.05).It mainly involves Malaria,cancer in cancer,HIF-1 signaling pathway,TNF signaling pathway,NOD-like receptor signaling pathway,PI3K-Akt signaling pathway,etc.Conclusion:Huanglian Jiedu Decoction"treats different diseases at the same time"coronary heart disease and type 2 diabetes have the characteristics of multiple components,multiple targets and multiple pathways,which provide theoretical basis for Huanglian Jiedu Decoction to treat coronary heart disease and type 2 diabetes in clinic,but the key targets and pathways of Huanglian Jiedu Decoction to treat diseases still need further experimental verification.
基金The work was supported by The Educational Research Project for Young and Middle-aged Teachers of Fujian Provincial Department of Education(JAT190982)The Open Research Project Funding Project of Fujian University Engineering Research Center of Biochemical Pharmaceuticals and The Innovation and Entrepreneurship Training Program for College Students of Fujian Province(S202012709029).
文摘Objective:To explore the active ingredients of Huanglian Jiedu Decoction(HLJD)for the treatment of COVID-19 and to further verify the combination mode.Methods:The TCMSP database was used to search for HLJD active ingredients and targets.COVID-19 targets were collected from GeneCards,DisGeNET and OMIM databases.Material-active-ingredients-targets(gene)network and targets protein-protein interaction network were constructed using Cytoscape 3.8.0 and the STRING database.GO functional enrichment analysis and KEGG pathway enrichment analysis of core targets were performed using R software.Cytoscape 3.8.0 was used to build“compound-targets-pathways”to predict HLJD mechanisms,and active ingredients were used as ligands to molecularly dock with SARS-CoV-23CL hydrolase,Spike glycoprotein and ACE2.The binding energy was calculated by molecular dynamics simulations and molecular mechanics Poisson-Boltzmann surface area method,and intermolecular interactions and the contribution of each residue to the binding free energy were analyzed.Results:Four medicinal materials,66 compounds and 219 targets were identified.It is found that the Protein-Protein Interaction core network contained 35 HLJD key targets proteins for COVID-19 treatment.705 GO functional enrichment entries(P<0.05)were produced;while KEGG pathway enrichment analysis identified 142 pathways(P<0.05)involving the Tumor Necrosis Factor signaling pathway and Interleukin-17 signaling pathway,etc.The binding energies of Kihadanin A,Palmidin A,Obacunone and Hispidone are much smaller than those of the currently reported clinical drugs with anti-SARS-CoV-2 drugs.The results of the binding energy indicate that van der Waals force is the main driving force for enzyme-substrate combination,whereas the electrostatic interaction and non-polar solvents contribute less.Conclusion:The“multi-component-multi-targets-multi-pathway”synergy of HLJD,which binds to SARSCoV-23CL hydrolase,Spike glycoprotein and ACE2,can act on targets Heat Shock Protein 90 Alpha Family Class A Member 1,Adrenoceptor Beta 2,Checkpoint Kinase 1,Peroxisome Proliferator-Activated Receptor Gamma and Mitogen-activated protein kinase 14 to regulate multiple signal pathways,and it may have a therapeutic effect on COVID-19.
基金supported by the Specialized Research Fund for the Doctoral Program of Higher Education(No.20113237120007)the Project supported by Jiangsu Province Traditional Chinese Medicine Administration of Science and Technology(No.LZ13001)the Project supported by the Natural Science Foundation of the Jiangsu Higher Education Institutions(No.12KJD360002)
文摘Huanglian Wendan decoction(HLWDD) has been used for the treatment of symptom of "Re", one of major causes in diabetes and metabolic disorders, according to the theory of traditional Chinese medicine. The present study aimed at investigating the cerebral protective effects of HLWDD on diabetic encephalopathy(DE), one of the major diabetic complications. The effects of HLWDD and metformin were analyzed in the streptozocin(STZ) + high-glucose-fat(HGF) diet-induced DE rats by gastric intubation. In the present study, the effects of HLWDD on cognition deficits were investigated after 30-day intervention at two daily dose levels(3 and 6 g·kg^(-1)). To explore the potential mechanisms underlying the effects of HLWDD, we detected the alterations of neuronal damages, inflammatory cytokines, and impaired insulin signaling pathway in hippocampus of the DE rats. Based on our results from the present study, we concluded that the protective effects of HLWDD against the cognitive deficits and neuronal damages through inhibiting the release of inflammatory cytokines and repairing insulin signaling pathway in hippocampus of the DE rats.
基金Program NCET Foundation NSFC(81230090)Global Research Network for Medicinal Plants and King Saud University,Shanghai Leading Academic Discipline Project(B906)+3 种基金Key laboratory of drug research for special environments,PLA,Shanghai Engineering Research Center for the Preparation of Bioactive Natural Products(10DZ2251300)Scientific Foundation of Shanghai China(12401900801,09DZ1975700,09DZ1971500,10DZ1971700)National Major Project of China(2011ZX09307-002-03)National Key Technology R&D Program of China(2012BAI29B06)
文摘Objective To develop a sensitive and rapid liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) method for the simultaneous determination of wogonin, coptisine, berberine, palmatine, jatrorrhizine, phellodendrine, magnoflorine, and wogonoside in rat plasma and to evaluate the pharmacokinetic characteristics of Huanglian Jiedu Decoction (HJD). Methods LC separation was performed on an Acquity HSS T3 column (100 mm × 2.1 mm, 1.8 μm) using gradient elution with the mobile phase consisting of acetonitrile and 0.1% formic acid water. The detection was accomplished by using positive electrospray ionization in multiple-reaction monitoring mode. Plasma samples were pretreated by protein precipitation. Results The method showed a good linearity over a wide concentration range (r^2 〉 0.99). The lower limits of quantification were 0.20 ng/mL for coptisine and phellodendrine, 0.48 ng/mL for berberine, 0.10 ng/mL for jatrorrhizine, 0.32 ng/mL for magnoflorine, 0.30 ng/mL for palmatine, and 4.80 ng/mL for wogonin and wogonoside, respectively. The intra- and inter-day precision of the analytes was less than 12.11%, while the accuracy was between -14.46% and 4.86%. The mean recovery of all the analytes ranged from 93.10% to 110.91%. Conclusion This validated method offers thee advantages of high sensitivity. It is successfully applied to evaluating the pharmacokinetic properties of HJD.
基金National Natural Science Foundation of P. R. China (No. 30371816)Specialized Research Fund for the Doctoral Program of Higher Education (No. 20030487008)
文摘Objective: To investigate the effects of Huanglian Jiedu Decoction (黄连解毒汤, HLJDD) on glucose transporter 4 (GLUT4) protein expressions in insulin-resistant murine target tissues. Methods: The experimental male Wistar rats were established into insulin resistant models by injecting streptozotocin (STZ 30 mg/kg) via caudal vein and feeding them with high fat high caloric diet, and randomly divided into the model group, the aspirin group and the HLJDD group. Besides, a normal group was set up for control. Changes of body weight (BW), levels of serum fasting blood glucose (FBG), serum fasting insulin (FINS) and oral glucose tolerance test (OGTT) were routinely determined. The expression of GLUT4 protein in adipose and skeletal muscle tissues before and after insulin stimulation was determined with Western blot. Results: In the HLJDD group after treatment, BW and FBG got decreased, OGTT improved, and the expression and translocation of GLUT4 protein elevated obviously, either before or after insulin stimulation, as compared with those in the model group, showing significant differences respectively. Conclusion: The mechanism of improving insulin resistance by HLJDD is probably associated with its effect in elevating GLUT4 protein expression and translocation in adipose and skeletal muscle tissues of insulin resistant rats.
基金Guangdong Provincial Medical Science and Technology Research Fund Project(No.A2019507)Traditional Chinese Medicine Bureau of Guangdong Provincial Project(No.20191117)+1 种基金Science and Technology Program of Guangzhou(No.202102020927)National Administration of Traditional Chinese Medicine Clinical Research Base Business Construction Research Project(No.JDZX2015241)。
文摘Objective:To evaluate the effect of heat-clearing and detoxifying method on the macrophages polarization in patients with acute myocardial infarction with heat toxin syndrome after intervention.Methods:Sixty patients with acute myocardial infarction and undergoing percutaneous coronary intervention with heat toxin syndrome were randomly divided into a control group and a test group with 30 cases each.The control group was given conventional treatment,and the test group was given Huanglian Jiedu Decoction,the representative of the method of clearing heat and detoxification,orally on the basis of the control group.The intervention time of both groups was 2 weeks.Comparing The Seattle Angina Pectoris Scale(SAQ)before and after treatment,creatine kinase(CK),creatine kinase MB isoenzyme(CKMB),high-sensitivity troponin I(hs-TnI),and Lipoprotein-associated phospholipaseA2(LPPLA_2)),the phenotype ratio of M1 and M2 macrophages,and observe the adverse reactions.Results:After treatment,the SAQ scores of the two groups of patients were improved,and the levels of CK,CK-MB,hs-TnI,and LP-PLA_2 decreased significantly.The scores of AS,AF,TS,and DP in the SAQ of the test group were all higher than those of the control group,and the hs-TnI and LP-PLA_2 were better than those of the control Group(P<0.05 or P<0.01).After treatment,the proportion of M1 type macrophages in the two groups of patients'macrophages decreased significantly(P<0.05 or P<0.01),the ratio of M2 type macrophages increased(P<0.05),and the M1/M2 ratio decreased.The ratio of M1/M2 in the test group of the control group was significantly lower than that of the control group(P<0.01).There were no obvious adverse reactions in both groups.Conclusions:The method of clearing heat and detoxifying has a definite effect on patients with acute myocardial infarction of heat toxin syndrome after interventional operation.It can reduce myocardial damage,improve myocardial function,and reduce inflammation.And it is safe for clinical treatment without any increasing risk of bleeding or other risk of cardiovascular events.
基金supported bythe Research Fund from Science and Technology Department of Guangdong Province(No.2014A020212277)the Specific Science and Technology Research Fund from Guangdong Province(No.YN2015QN07)
文摘Background Sepsis is a complex pathophysiologic process, which is the leading cause of death in the world. Many studies have revealed that Chinese medicine has shown tremendous advantages on the treatment of sepsis. Our study aims to explore the effect of Huanglian jiedu decoction and Jiawei huanglian jiedu decoction on organ function in septic rats. Methods SD rats were randomly divided into 7 groups, sham-group, cecal ligation and puncture group (CLP, 18h/72h), Jiawei huanglian jiedu decoction group (JW, 18h/72h), Huanglian jiedu decoc-tion group (W, 18h/72h). Except the Sham group, the rats in other groups received cecal ligation and puncture method to induce sepsis. CLP groups were intragastric administration with normal saline after CLP. Huanglian jiedu decoction and Jiawei huanglian jiedu decoction groups were intragastric administration with Huanglian jie-du decoction and Jiawei huanglian jiedu decoction in the same time points. Glutamic-pyruvic transaminase (ALT), glutamic oxalacetic transaminase (AST), total bilirubin (TBIL), creatinine(Cr), urea, creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH) were detected by biochemical analyzer. Brain natriuretic peptide (BNP), surfactant protein A (SP-A), chemotactic factor for monocyte-1 (MCP-1), D-lactic acid (D-LAC), complement 5a, mobility group box-1 protein B 1 (HMGB-1), interleukin 6 (IL-6) were analyzed by enzyme-linked immunosor-bent assay (ELISA). Total lung capacity (TLC) and function residual capacity (FRC) were measured by buxco re-search system. The wet to dry weight ratio (W/D) was tested. Moreover, changes in tissue pathology were evaluat-ed using hematoxylin and eosin (H&E) staining and electron microscope. Results The level of AST/ALT in se-rum was decreased after treatment with Huanglian jiedu decoction and Jiawei huanglian jiedu decoction. More-over, the level of TLC and FRC was significantly increased, and the level of SP-A, W/D was significantly de-creased. In addition, the level of CK-MB, IL-6, HMGB-1 and MCP-1 in serum was decreased. Inflammation fac-tors were positively correlated with lung function, and the cardiac function was positively correlated with the or-gan function, the differences were statistically significant. In addition, the histological alterations of myocardium, lung and intestine were attenuated after treatment with Huanglian jiedu decoction and Jiawei huanglian jiedu de-coction. Conclusion Huanglian jiedu decoction and Jiawei huanglian jiedu decoction can inhibit the inflamma-tory infiltration of septic rats and improve organ function.
基金supported by Research Foundation of Education Bureau of Hunan Province (NO.19B377)。
文摘Background Huanglian Jiedu Decoction(HJD) is a typical traditional Chinese medicine which exhibits diverse curative effects against different kinds of diseases because of its multi-components and multi-targets. It has been widely used for the treatment of sepsis. However, the underlying molecular mechanism is still unclear.Methods Network pharmacology was applied to analyze the potential active ingredients and molecular mechanism of HJD in the treatment of sepsis.Results As a result, we totally found 102 active ingredients and 221 corresponding targets. Among them, 117 were hit by the 1 837 targets associated with sepsis. Our further analysis demonstrated 57 drug and disease intersection targets. Based on Gene Ontology(GO) enrichment analysis, 2176 biological process terms, 84 molecular function terms and 28 cellular component terms were acquired. By performing Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis, we acquired the dominating signaling pathways associated with sepsis. By constructing protein-protein interaction network of common targets, 11 hub genes were identified.Conclusions Taken together, our results indicated that HJD may protect against sepsis via a mechanism involving multiple targets and pathways.