[Objectives]To explore the molecular mechanism of Zhizi Ganjiang Decoction(ZZGJD)regulating sleep disorders based on the network pharmacology.[Methods]The BATMAN-TCM server was used to predict the potential targets of...[Objectives]To explore the molecular mechanism of Zhizi Ganjiang Decoction(ZZGJD)regulating sleep disorders based on the network pharmacology.[Methods]The BATMAN-TCM server was used to predict the potential targets of ZZGJD and constructed a compound-disease-target network map,and the GeneCards database was used to search for insomnia-related targets;with the aid of Cytoscape 3.5.1 software,the compound-insomnia target interaction network and protein-protein interaction(PPI)network were constructed,and gene ontology(GO)enrichment,Reactome pathway enrichment,and biological pathway enrichment analysis based on KEGG(Kyoto Encyclopedia of Genes and Enomes)was performed.[Results]The constructed PPI network of ZZGJD involves 204 nodes and 645 interaction relationships.Key nodes involve G protein-coupled receptors,rhodopsin-like adrenaline receptor families,zinc finger proteins,nuclear hormone receptor superfamilies,ligand-binding domains of hormone receptors,voltage-gated calcium(Ca^(2+))channel IQ domains,and neuropituitary hormones.The related entries of GO enrichment analysis pathway mainly involve G protein-coupled receptor activity,neurotransmitter receptor activity,adrenergic receptor activity,ammonium ion binding,catecholamine binding,G protein-coupled serotonin receptor activity,serotonin receptor activity,and steroid hormone receptors(SHRs)activity.Reactome pathway mainly involves amine ligand binding receptors,rhodopsin-like receptors,G protein-coupled receptor ligand binding,adrenergic receptors,neuronal systems and signal transduction,etc.KEGG channel analysis mainly involves neural activity ligand-receptor interaction,calcium ion messenger pathway,cAMP signaling pathway,serotonergic synapse,dopaminergic synapse,cGMP-PKG signaling pathway,and cholinergic synapse pathway,etc.[Conclusions]The potential targets of ZZGJD in the treatment of insomnia mainly involve G protein-coupled receptors,and regulate various neural receptor pathways such as calcium ion channels,serotonin,dopamine,and adrenergic receptors.INS,IGF-1,CTNNB1,ESR1,HIF-1A,etc.may be the key targets of ZZGJD in regulating sleep disorders,reflecting the multi-target and overall function characteristics of Chinese herbal compounds.ZZGJD is of great significance in the treatment of sleep disorders caused by blood sugar abnormality in patients with diabetes and perimenopausal hormones in women.This article is expected to It provide new ideas for in-depth study of the molecular mechanism of ZZGJD.展开更多
[Objectives]To explore the molecular mechanism of Zhizi Ganjiang Decoction in the treatment of liver cirrhosis based on the network pharmacology.[Methods]The BATMAN-TCM server was used to predict the potential targets...[Objectives]To explore the molecular mechanism of Zhizi Ganjiang Decoction in the treatment of liver cirrhosis based on the network pharmacology.[Methods]The BATMAN-TCM server was used to predict the potential targets of Zhizi Ganjiang Decoction,and the GeneCards database searched for targets related to liver cirrhosis;Cytoscape 3.5.1 software was used to construct compound-cirrhosis target interaction network and protein interaction network;then gene ontology(GO)enrichment analysis,Reactome pathway enrichment analysis,and KEGG-based biological pathway enrichment analysis were performed.[Results]The compound-disease-target network of Zhizi Ganjiang Decoction was constructed.The PPI network of Zhizi Ganjiang Decoction targets constructed based on String contained 130 nodes and 689 interaction relationships.The key nodes mainly involved nuclear hormone receptor-like domain superfamily and ligand binding domain,serpentine type 7TM GPCR chemoreceptor and chemoreceptor Srx,rhodopsin family transmembrane receptors,zinc finger NHR/GATA type nuclear hormone receptors and ligand binding domains,PI3-kinase family p85 binding domain,phosphoinositide(PI)3-kinase catalytic domain and other categories.GO enrichment analysis pathway related entries mainly involved steroid hormone receptor activity,nuclear receptor activity,transcription factor activity,direct ligands regulation sequence-specific DNA binding,G protein-coupled amine receptor activity,steroid binding,catecholamine binding,neurotransmitter receptor activity,adrenergic receptor activity,ammonium ion binding,and oxidoreductase activity,etc.KEGG channel analysis mainly involved neuroactive ligand-receptor interaction,aldosterone regulates sodium reabsorption,regulates lipolysis in adipocytes,regulates inflammatory mediators of TRP channels,tyrosine metabolism,calcium signaling pathway,cAMP signaling pathway,and nonalcoholic fatty liver diseases.[Conclusions]The research results suggest that Zhizi Ganjiang Decoction regulates the process of liver cirrhosis mainly through aldosterone regulation of sodium reabsorption,regulation of lipolysis in adipocytes,regulation of inflammatory mediators of TRP channels,calcium signaling pathways,and nonalcoholic fatty liver diseases.This reflects the multi-target and holistic action characteristics of the Chinese herbal compounds,and is expected to provide new ideas for further research on the molecular mechanism of Zhizi Ganjiang Decoction.展开更多
OBJECTIVE:To evaluate the protective effect of Zhizi Huangqi Shanzha formula(栀子黄芪山楂方,ZHSF)on aflatoxin-induced liver injury.METHODS:The protective effect of ZHSF on the aflatoxin-induced liver injury was evalua...OBJECTIVE:To evaluate the protective effect of Zhizi Huangqi Shanzha formula(栀子黄芪山楂方,ZHSF)on aflatoxin-induced liver injury.METHODS:The protective effect of ZHSF on the aflatoxin-induced liver injury was evaluated by histological observation,blood cell analysis,evaluation of liver function and immunity,and gut microbiota analysis.RESULTS:ZHSF can significantly up-regulate the percentage of lymphocytes and eosinophils in the blood of Aflatoxin B1-intoxicated mice,down-regulate the levels of serum aspartate aminotransferase,alanine aminotransferase,and malondialdehyde,and recover the liver tissue structure.Aflatoxin poisoning induces a variation of the intestinal flora of mice,and ZHSF may recover the variation of intestinal flora induced by Aflatoxin B1.Cluster analysis showed that the intestinal flora of mice in the intervention group was more similar to that of the control group.Correlation analysis showed that Lachnospiraceae,Desulfovibrio,and Lactobacillus may be the key flora for the pharmacological effects of ZHSF.CONCLUSIONS:ZHSF may protect against aflatoxininduced liver damage,improve immunity,and inhibit oxidative stress by regulating the composition and relative abundance of intestinal flora,which makes it a promising liver-protective candidate drug.展开更多
Objective: To investigate the effects of Zhizi Chuanxiong Capsule(ZCC, 栀子川芎胶囊) on abnormal DNA methylation in a rabbit model of atherosclerosis(AS). Methods: After 1 week of adaptive feeding, 48 New Zealan...Objective: To investigate the effects of Zhizi Chuanxiong Capsule(ZCC, 栀子川芎胶囊) on abnormal DNA methylation in a rabbit model of atherosclerosis(AS). Methods: After 1 week of adaptive feeding, 48 New Zealand white rabbits were randomly divided into 4 groups: a control group(n=12) fed with normal diet for 22 weeks; a model group(n=12) fed with high fat diet for 14 weeks followed by 8 weeks of normal diet feeding; a low-dose ZCC group(n=12) fed with high fat diet and low-dose ZCC for 14 weeks, followed by 8 weeks of normal diet and low-dose drug; a high-dose ZCC group(n=12) fed with high fat diet and high-dose drug for 14 weeks, followed by 8 weeks of normal diet and high-dose drug. After 22 weeks of feeding, blood samples were taken from the rabbit ear vein, and the genomic DNA was extracted for methylation immunoprecipitation sequencing(Medip-seq). The aorta tissues were collected for hematoxylin-eosin(HE) staining. Results: Eight rabbits died during the feeding process. HE staining showed that the size of the lipid deposition on vessel wall and atherosclerotic plaque formation were reduced in both low-and high-dose group. The Medip-seq results showed that there were 146 abnormally methylated genes(including both hypermethylated gene and hypomethylated genes) in the model group, compared with the control group. Gene Ontology(GO) and Pathway analysis showed that these abnormally methylated genes were found to be involved in multiple AS-related functions and pathways, such as protein kinase C activity, cholesterol transport, mitogen-activated protein kinase(MAPK) signaling pathway, peroxisome proliferater-activated receptor signaling pathway, vascular smooth muscle contraction, inflammation and so on. The abnormal methylated genes in AS model group were altered in both low-and high-dose groups: low-dose ZCC could change 72 of the 146 abnormally methylated genes, highdose ZCC could change 71. Through GO and Pathway analysis, these altered methylated genes were involved in protein kinase C activity, inflammatory pathway, MAPK signaling pathway, vascular endothelial growth factor signaling pathway, etc. Conclusion: ZCC could treat AS through regulating the abnormal hypermethylated and hypomethylated genes in AS rabbit model.展开更多
Objectives: Gardenia Jasminoides Ellis(Zhizi), belonging to Rubiaceae family, has been traditionally used for treatment cholestasis and jaundice for centuries in Asian countries. In the theory of Traditional Chines...Objectives: Gardenia Jasminoides Ellis(Zhizi), belonging to Rubiaceae family, has been traditionally used for treatment cholestasis and jaundice for centuries in Asian countries. In the theory of Traditional Chinese Medicines, Zhizi could dispel dampness and heat via the urine to execute its choleretic effects. However, the potential molecular mechanism has been still poorly clarified. Here, we investigated the effect of different dose of Zhizi aqueous extract powder(0.3 g/kg/d and 0.9 g/kg/d) on urinary excretion of bile acids(BAs), and defined the potential mechanism via renal BAs efflux transporters Mrp2 and Mrp4 in normal rats.Methods: Male Wistar rats were orally administrated with 0.3 or 0.9 g/kg/d dose of Zhizi aqueous extract powder for 2 weeks, then body weight, serum aminotransferase, total BAs concentrations in liver, bile,serum, kidney and urine, 1 h bile flow, 12-h urinary volume, biliary and urinary excretion amount of total BAs as well as protein expression of major renal BAs efflux transporter Mrp2 and Mrp4, were all evaluated.Results: Zhizi especially the high dose of Zhizi aqueous extract powder could reduce hepatic total BAs concentration. Additionally, bile flow and biliary excretion had no significant difference, but the remarkable increasing urinary excretion of BAs and 2 to 3 folds up-regulated renal Mrp2 expression were observed after administrated with Zhizi as compared with the control group.Conclusion: The findings indicate that Zhizi reduces hepatic total BAs level by increasing urinary excretion rather than the biliary excretion of BAs, which, in turn ascribed to elevated protein expression of Mrp2 at apical membrane of renal tubular epithelial cells.展开更多
文摘[Objectives]To explore the molecular mechanism of Zhizi Ganjiang Decoction(ZZGJD)regulating sleep disorders based on the network pharmacology.[Methods]The BATMAN-TCM server was used to predict the potential targets of ZZGJD and constructed a compound-disease-target network map,and the GeneCards database was used to search for insomnia-related targets;with the aid of Cytoscape 3.5.1 software,the compound-insomnia target interaction network and protein-protein interaction(PPI)network were constructed,and gene ontology(GO)enrichment,Reactome pathway enrichment,and biological pathway enrichment analysis based on KEGG(Kyoto Encyclopedia of Genes and Enomes)was performed.[Results]The constructed PPI network of ZZGJD involves 204 nodes and 645 interaction relationships.Key nodes involve G protein-coupled receptors,rhodopsin-like adrenaline receptor families,zinc finger proteins,nuclear hormone receptor superfamilies,ligand-binding domains of hormone receptors,voltage-gated calcium(Ca^(2+))channel IQ domains,and neuropituitary hormones.The related entries of GO enrichment analysis pathway mainly involve G protein-coupled receptor activity,neurotransmitter receptor activity,adrenergic receptor activity,ammonium ion binding,catecholamine binding,G protein-coupled serotonin receptor activity,serotonin receptor activity,and steroid hormone receptors(SHRs)activity.Reactome pathway mainly involves amine ligand binding receptors,rhodopsin-like receptors,G protein-coupled receptor ligand binding,adrenergic receptors,neuronal systems and signal transduction,etc.KEGG channel analysis mainly involves neural activity ligand-receptor interaction,calcium ion messenger pathway,cAMP signaling pathway,serotonergic synapse,dopaminergic synapse,cGMP-PKG signaling pathway,and cholinergic synapse pathway,etc.[Conclusions]The potential targets of ZZGJD in the treatment of insomnia mainly involve G protein-coupled receptors,and regulate various neural receptor pathways such as calcium ion channels,serotonin,dopamine,and adrenergic receptors.INS,IGF-1,CTNNB1,ESR1,HIF-1A,etc.may be the key targets of ZZGJD in regulating sleep disorders,reflecting the multi-target and overall function characteristics of Chinese herbal compounds.ZZGJD is of great significance in the treatment of sleep disorders caused by blood sugar abnormality in patients with diabetes and perimenopausal hormones in women.This article is expected to It provide new ideas for in-depth study of the molecular mechanism of ZZGJD.
文摘[Objectives]To explore the molecular mechanism of Zhizi Ganjiang Decoction in the treatment of liver cirrhosis based on the network pharmacology.[Methods]The BATMAN-TCM server was used to predict the potential targets of Zhizi Ganjiang Decoction,and the GeneCards database searched for targets related to liver cirrhosis;Cytoscape 3.5.1 software was used to construct compound-cirrhosis target interaction network and protein interaction network;then gene ontology(GO)enrichment analysis,Reactome pathway enrichment analysis,and KEGG-based biological pathway enrichment analysis were performed.[Results]The compound-disease-target network of Zhizi Ganjiang Decoction was constructed.The PPI network of Zhizi Ganjiang Decoction targets constructed based on String contained 130 nodes and 689 interaction relationships.The key nodes mainly involved nuclear hormone receptor-like domain superfamily and ligand binding domain,serpentine type 7TM GPCR chemoreceptor and chemoreceptor Srx,rhodopsin family transmembrane receptors,zinc finger NHR/GATA type nuclear hormone receptors and ligand binding domains,PI3-kinase family p85 binding domain,phosphoinositide(PI)3-kinase catalytic domain and other categories.GO enrichment analysis pathway related entries mainly involved steroid hormone receptor activity,nuclear receptor activity,transcription factor activity,direct ligands regulation sequence-specific DNA binding,G protein-coupled amine receptor activity,steroid binding,catecholamine binding,neurotransmitter receptor activity,adrenergic receptor activity,ammonium ion binding,and oxidoreductase activity,etc.KEGG channel analysis mainly involved neuroactive ligand-receptor interaction,aldosterone regulates sodium reabsorption,regulates lipolysis in adipocytes,regulates inflammatory mediators of TRP channels,tyrosine metabolism,calcium signaling pathway,cAMP signaling pathway,and nonalcoholic fatty liver diseases.[Conclusions]The research results suggest that Zhizi Ganjiang Decoction regulates the process of liver cirrhosis mainly through aldosterone regulation of sodium reabsorption,regulation of lipolysis in adipocytes,regulation of inflammatory mediators of TRP channels,calcium signaling pathways,and nonalcoholic fatty liver diseases.This reflects the multi-target and holistic action characteristics of the Chinese herbal compounds,and is expected to provide new ideas for further research on the molecular mechanism of Zhizi Ganjiang Decoction.
基金the Provincial Natural Science Foundation of Anhui Province-Quantitative Constitutive Effect and Mechanism of Action of Dendrobium Polysaccharides against Tumours based on the Tumour Microenvironment(2208085QH273)Natural Science Research Project for Anhui Universities-mechanism of Anti-bacterial Diarrhea Effect of Probiotic-fermented Portulaca Oleracea in Targeting and Regulating Amino acid Metabolism of Intestinal Flora and Screening of Anti-tumor Active Fraction of Paris polyphylla and its Effect on the Tumour Immune Microenvironment(2023AH052634,2022AH051668)。
文摘OBJECTIVE:To evaluate the protective effect of Zhizi Huangqi Shanzha formula(栀子黄芪山楂方,ZHSF)on aflatoxin-induced liver injury.METHODS:The protective effect of ZHSF on the aflatoxin-induced liver injury was evaluated by histological observation,blood cell analysis,evaluation of liver function and immunity,and gut microbiota analysis.RESULTS:ZHSF can significantly up-regulate the percentage of lymphocytes and eosinophils in the blood of Aflatoxin B1-intoxicated mice,down-regulate the levels of serum aspartate aminotransferase,alanine aminotransferase,and malondialdehyde,and recover the liver tissue structure.Aflatoxin poisoning induces a variation of the intestinal flora of mice,and ZHSF may recover the variation of intestinal flora induced by Aflatoxin B1.Cluster analysis showed that the intestinal flora of mice in the intervention group was more similar to that of the control group.Correlation analysis showed that Lachnospiraceae,Desulfovibrio,and Lactobacillus may be the key flora for the pharmacological effects of ZHSF.CONCLUSIONS:ZHSF may protect against aflatoxininduced liver damage,improve immunity,and inhibit oxidative stress by regulating the composition and relative abundance of intestinal flora,which makes it a promising liver-protective candidate drug.
基金Supported by National Natural Science Foundation of China(No.81603490)China Post Doctoral Science Foundation(No.2016M590187)
文摘Objective: To investigate the effects of Zhizi Chuanxiong Capsule(ZCC, 栀子川芎胶囊) on abnormal DNA methylation in a rabbit model of atherosclerosis(AS). Methods: After 1 week of adaptive feeding, 48 New Zealand white rabbits were randomly divided into 4 groups: a control group(n=12) fed with normal diet for 22 weeks; a model group(n=12) fed with high fat diet for 14 weeks followed by 8 weeks of normal diet feeding; a low-dose ZCC group(n=12) fed with high fat diet and low-dose ZCC for 14 weeks, followed by 8 weeks of normal diet and low-dose drug; a high-dose ZCC group(n=12) fed with high fat diet and high-dose drug for 14 weeks, followed by 8 weeks of normal diet and high-dose drug. After 22 weeks of feeding, blood samples were taken from the rabbit ear vein, and the genomic DNA was extracted for methylation immunoprecipitation sequencing(Medip-seq). The aorta tissues were collected for hematoxylin-eosin(HE) staining. Results: Eight rabbits died during the feeding process. HE staining showed that the size of the lipid deposition on vessel wall and atherosclerotic plaque formation were reduced in both low-and high-dose group. The Medip-seq results showed that there were 146 abnormally methylated genes(including both hypermethylated gene and hypomethylated genes) in the model group, compared with the control group. Gene Ontology(GO) and Pathway analysis showed that these abnormally methylated genes were found to be involved in multiple AS-related functions and pathways, such as protein kinase C activity, cholesterol transport, mitogen-activated protein kinase(MAPK) signaling pathway, peroxisome proliferater-activated receptor signaling pathway, vascular smooth muscle contraction, inflammation and so on. The abnormal methylated genes in AS model group were altered in both low-and high-dose groups: low-dose ZCC could change 72 of the 146 abnormally methylated genes, highdose ZCC could change 71. Through GO and Pathway analysis, these altered methylated genes were involved in protein kinase C activity, inflammatory pathway, MAPK signaling pathway, vascular endothelial growth factor signaling pathway, etc. Conclusion: ZCC could treat AS through regulating the abnormal hypermethylated and hypomethylated genes in AS rabbit model.
基金supported by the Prof. Xinan Wu’s,Dr. Yuhui Wei’s and Mr Guoqiang Zhang’s National Natural Science Foundation of China (Number:81373494,81373927,81641142 and 81702853)
文摘Objectives: Gardenia Jasminoides Ellis(Zhizi), belonging to Rubiaceae family, has been traditionally used for treatment cholestasis and jaundice for centuries in Asian countries. In the theory of Traditional Chinese Medicines, Zhizi could dispel dampness and heat via the urine to execute its choleretic effects. However, the potential molecular mechanism has been still poorly clarified. Here, we investigated the effect of different dose of Zhizi aqueous extract powder(0.3 g/kg/d and 0.9 g/kg/d) on urinary excretion of bile acids(BAs), and defined the potential mechanism via renal BAs efflux transporters Mrp2 and Mrp4 in normal rats.Methods: Male Wistar rats were orally administrated with 0.3 or 0.9 g/kg/d dose of Zhizi aqueous extract powder for 2 weeks, then body weight, serum aminotransferase, total BAs concentrations in liver, bile,serum, kidney and urine, 1 h bile flow, 12-h urinary volume, biliary and urinary excretion amount of total BAs as well as protein expression of major renal BAs efflux transporter Mrp2 and Mrp4, were all evaluated.Results: Zhizi especially the high dose of Zhizi aqueous extract powder could reduce hepatic total BAs concentration. Additionally, bile flow and biliary excretion had no significant difference, but the remarkable increasing urinary excretion of BAs and 2 to 3 folds up-regulated renal Mrp2 expression were observed after administrated with Zhizi as compared with the control group.Conclusion: The findings indicate that Zhizi reduces hepatic total BAs level by increasing urinary excretion rather than the biliary excretion of BAs, which, in turn ascribed to elevated protein expression of Mrp2 at apical membrane of renal tubular epithelial cells.