[Objectives]To investigate the ameliorative effects of Huanglian Jiedu Decoction(HLJDD)on cognitive function impairment in an Alzheimer s disease(AD)mouse model induced by Porphyromonas gingivalis infection.[Methods]T...[Objectives]To investigate the ameliorative effects of Huanglian Jiedu Decoction(HLJDD)on cognitive function impairment in an Alzheimer s disease(AD)mouse model induced by Porphyromonas gingivalis infection.[Methods]Thirty-six male C57BL/6 mice were randomly assigned to six groups:control group,model group,low-dose HLJDD group,medium-dose HLJDD group,high-dose HLJDD group,and positive drug group(treated with moxifloxacin).With the exception of the control group,all groups underwent an 8-week P.gingivalis chronic infection model induced via oral administration.Subsequently,each treatment group received corresponding doses of HLJDD(2.5,5,and 10 mg/g)or moxifloxacin for 8 weeks intervention.The novel object recognition test was employed to evaluate the non-spatial memory abilities of mice,and the novel object exploration preference index was calculated to assess cognitive function.[Results]Compared to the control group,the novel object exploration preference index of mice in the model group was significantly reduced(P<0.01),indicating that P.gingivalis infection effectively induced cognitive impairment.Relative to the model group,mice treated with medium and high doses of HLJDD exhibited a significant,dose-dependent increase in the novel object exploration preference index,whereas the low-dose group showed no significant improvement.Additionally,the positive drug moxifloxacin demonstrated a significant neuroprotective effect on cognition.[Conclusions]HLJDD effectively improves cognitive function impairment in AD model mice induced by P.gingivalis infection,offering novel experimental evidence supporting the heat-clearing and detoxification approach as well as the therapeutic potential of traditional Chinese medicine(TCM)compounds in the intervention of AD.展开更多
[Objectives]To explore the possible targets of Huanglian Jiedu Decoction in NLRP3/IFITM3/γ-secretase pathway through regulating iron homeostasis and the potential mechanism of anti-Alzheimer s disease(AD).[Methods]Fi...[Objectives]To explore the possible targets of Huanglian Jiedu Decoction in NLRP3/IFITM3/γ-secretase pathway through regulating iron homeostasis and the potential mechanism of anti-Alzheimer s disease(AD).[Methods]Firstly,the active components and related targets of Huanglian Jiedu Decoction were predicted in the database of Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and the targets of AD were collected from Genecards,OMIM and MalaCards databases.Genes inhibiting iron homeostasis were obtained from the ferroptosis Database(FerrDB).Then,Huanglian Jiedu Decoction the interactive genes of the active component target,the AD target and the iron homeostasis target.Next,the protein-protein interaction(PPI)network of interactive genes was constructed,and the software Cytoscape 3.9.1 was used to visualize and screen out the key active components and target genes.Finally,Gene Ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were performed.[Results]A total of 51 Huanglian Jiedu Decoction components and 247 potential protein targets were identified,including 1942 AD targets,369 iron homeostasis regulatory genes,and 18 intersection targets.Eleven key targets including CDKN2A,MAPK1,TGFβ1,MAPK14,TP53,EGFR,GSK3β,PTEN,HIF1α,HMOX1 and PRKCαwere identified by PPI network analysis.[Conclusions]In the regulation of iron homeostasis in AD by Huanglian Jiedu Decoction,CDKN2A,MAPK1,TGFβ1,MAPK14,TP53,EGFR,GSK3β,PTEN,HIF1α,HMOX1 and PRKCαmay be involved,involving ErbB signaling pathway,endocrine resistance signaling pathway,HIF-1 signaling pathway and so on.展开更多
[Objectives]The paper was to investigate the mechanism by which Pereskia aculeata Mill.regulates ferroptosis and interferes with colon cancer using network pharmacology.[Methods]The effect of P.aculeata on HCT116 cell...[Objectives]The paper was to investigate the mechanism by which Pereskia aculeata Mill.regulates ferroptosis and interferes with colon cancer using network pharmacology.[Methods]The effect of P.aculeata on HCT116 cells was observed by examining cell morphology.The intersection of P.aculeata,colon cancer,and ferroptosis targets was determined using the Venny 2.1.0 online platform.DAVID database was used to perform GO and KEGG enrichment analyses.Cytoscape_v3.10.0 was used for network mapping and PPI analysis.[Results]The observation of cell morphology indicated that P.aculeata suppressed the growth of HCT116 cells.GO and KEGG analysis identified 67 genes involved in potential pathways,including the MAPK signaling pathway and Apoptosis,18 of which were located on the MAPK pathway.After conducting PPI visualization analysis and ranking based on Degree values,we identified TP53,TNF,EGFR,MAPK14,and AKT1 as the top five targets with the highest Degree values.[Conclusions]P.aculeata may activate the p53 gene through the MAPK signaling pathway,inducing ferroptosis and ultimately resulting in tumor cell death.展开更多
基金Supported by National Natural Science Foundation of China(82160832)Natural Science Foundation of Guangxi Zhuang Autonomous Region(2017GXNS-FAA198255)+2 种基金Open Project of Guangxi Key Laboratory of Brain and Cognitive Neuroscience(GKLBCN-202206-02)Guangxi Undergraduate Innovation and Entrepreneurship Training Program(202410601029,S202410601113)The 4th Thousand Young and Middle-Aged Backbone Teachers Cultivation Program of Guangxi Higher Education Institutions.
文摘[Objectives]To investigate the ameliorative effects of Huanglian Jiedu Decoction(HLJDD)on cognitive function impairment in an Alzheimer s disease(AD)mouse model induced by Porphyromonas gingivalis infection.[Methods]Thirty-six male C57BL/6 mice were randomly assigned to six groups:control group,model group,low-dose HLJDD group,medium-dose HLJDD group,high-dose HLJDD group,and positive drug group(treated with moxifloxacin).With the exception of the control group,all groups underwent an 8-week P.gingivalis chronic infection model induced via oral administration.Subsequently,each treatment group received corresponding doses of HLJDD(2.5,5,and 10 mg/g)or moxifloxacin for 8 weeks intervention.The novel object recognition test was employed to evaluate the non-spatial memory abilities of mice,and the novel object exploration preference index was calculated to assess cognitive function.[Results]Compared to the control group,the novel object exploration preference index of mice in the model group was significantly reduced(P<0.01),indicating that P.gingivalis infection effectively induced cognitive impairment.Relative to the model group,mice treated with medium and high doses of HLJDD exhibited a significant,dose-dependent increase in the novel object exploration preference index,whereas the low-dose group showed no significant improvement.Additionally,the positive drug moxifloxacin demonstrated a significant neuroprotective effect on cognition.[Conclusions]HLJDD effectively improves cognitive function impairment in AD model mice induced by P.gingivalis infection,offering novel experimental evidence supporting the heat-clearing and detoxification approach as well as the therapeutic potential of traditional Chinese medicine(TCM)compounds in the intervention of AD.
基金Supported by National Natural Science Foundation of China(82160832)Natural Science Foundation of Guangxi Zhuang Autonomous Region(2022GXNSFAA035603&2017GXNSFAA198255)+1 种基金the Open Project Program of Guangxi Key Laboratory of Brain and Cognitive Neuroscience,Guilin Medical University(GKLBCN-202206-02)the Fourth Training Plan of Thousands of Young and Mid-aged Mainstay Teachers in Guangxi Colleges and Universities.
文摘[Objectives]To explore the possible targets of Huanglian Jiedu Decoction in NLRP3/IFITM3/γ-secretase pathway through regulating iron homeostasis and the potential mechanism of anti-Alzheimer s disease(AD).[Methods]Firstly,the active components and related targets of Huanglian Jiedu Decoction were predicted in the database of Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and the targets of AD were collected from Genecards,OMIM and MalaCards databases.Genes inhibiting iron homeostasis were obtained from the ferroptosis Database(FerrDB).Then,Huanglian Jiedu Decoction the interactive genes of the active component target,the AD target and the iron homeostasis target.Next,the protein-protein interaction(PPI)network of interactive genes was constructed,and the software Cytoscape 3.9.1 was used to visualize and screen out the key active components and target genes.Finally,Gene Ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were performed.[Results]A total of 51 Huanglian Jiedu Decoction components and 247 potential protein targets were identified,including 1942 AD targets,369 iron homeostasis regulatory genes,and 18 intersection targets.Eleven key targets including CDKN2A,MAPK1,TGFβ1,MAPK14,TP53,EGFR,GSK3β,PTEN,HIF1α,HMOX1 and PRKCαwere identified by PPI network analysis.[Conclusions]In the regulation of iron homeostasis in AD by Huanglian Jiedu Decoction,CDKN2A,MAPK1,TGFβ1,MAPK14,TP53,EGFR,GSK3β,PTEN,HIF1α,HMOX1 and PRKCαmay be involved,involving ErbB signaling pathway,endocrine resistance signaling pathway,HIF-1 signaling pathway and so on.
基金Supported by National Natural Science Foundation of China(82160832)the Open Project Program of Guangxi Key Laboratory of Brain and Cognitive Neuroscience,Guilin Medical University(GKLBCN-202206-02)+2 种基金Annual Scientific Research Project of Guangdong Provincial Administration of Traditional Chinese Medicine in 2022(20222138)the Fourth Training Plan for Thousands of Young and Mid-aged Mainstay Teachers in Guangxi Colleges and Universitiesthe Innovation and Entrepreneurship Training Program for College Students in Guilin Medical University in 2023(X202310601232,S202310601140,202210601214).
文摘[Objectives]The paper was to investigate the mechanism by which Pereskia aculeata Mill.regulates ferroptosis and interferes with colon cancer using network pharmacology.[Methods]The effect of P.aculeata on HCT116 cells was observed by examining cell morphology.The intersection of P.aculeata,colon cancer,and ferroptosis targets was determined using the Venny 2.1.0 online platform.DAVID database was used to perform GO and KEGG enrichment analyses.Cytoscape_v3.10.0 was used for network mapping and PPI analysis.[Results]The observation of cell morphology indicated that P.aculeata suppressed the growth of HCT116 cells.GO and KEGG analysis identified 67 genes involved in potential pathways,including the MAPK signaling pathway and Apoptosis,18 of which were located on the MAPK pathway.After conducting PPI visualization analysis and ranking based on Degree values,we identified TP53,TNF,EGFR,MAPK14,and AKT1 as the top five targets with the highest Degree values.[Conclusions]P.aculeata may activate the p53 gene through the MAPK signaling pathway,inducing ferroptosis and ultimately resulting in tumor cell death.
