Exploring the potential mechanisms of luteolin against ulcerative colitis and colorectal cancer via network pharmacology and molecular docking

Background:Patients diagnosed with ulcerative colitis(UC)are known to have an increased susceptibility to colorectal cancer(CRC).However,the shared underlying mechanisms between UC and CRC remain unclear.Given the therapeutic potential of luteolin in both UC and CRC,this study aims to elucidate the molecular targets and mechanisms through which luteolin exerts its effects against these diseases.Methods:The GeneCards database,DisGENet database,and Gene Expression Omnibus database were utilized to analyze the targets associated with UC and CRC.Subsequently,the Traditional Chinese Medicine Systems Pharmacology and SwissTargetPrediction databases were employed to identify luteolin-related targets.The identified luteolin-related targets were then mapped to official gene symbols using the UniProt database.The Cytoscape 3.9.0 software was utilized to construct a network of luteolin-associated targets.Venn diagram analysis was performed to identify common targets among UC,CRC,and luteolin.The common targets were further analyzed using the STRING database to construct a protein-protein interaction network.The“cytoHubba”plugin in Cytoscape 3.9.0 was employed to identify hub targets within the PPI network.Gene Ontology functional analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were conducted on the hub targets.Finally,molecular docking using AutoDock and PyMOL software was performed to assess the binding affinity between luteolin and the hub targets.Results:Luteolin was found to interact with a total of 149 pharmacological targets,while UC and CRC were associated with 1232 and 3278 targets,respectively.Forty-six common targets were identified among luteolin,UC,and CRC.Through the application of seven different algorithms,seven hub targets were identified,TP53,AKT1,TNF,SRC,EGFR,and MMP9.Bioinformatics enrichment analysis revealed 49 enriched pathways through Kyoto Encyclopedia of Genes and Genomes analysis,while Gene Ontology analysis yielded a total of 245 biological processes,4 cellular components,and 7 molecular functions.Molecular docking simulations demonstrated a good binding affinity between luteolin and the hub targets.Conclusion:This study identified multiple potential pharmacological targets and elucidated various biological pathways through which luteolin may exert its therapeutic effects in the treatment of UC and CRC.These findings provide a solid theoretical foundation for further experimental investigations in the treatment of UC and CRC.

Suitable soil moisture contents for water use efficiency and saponins accumulation in Panax notoginseng

Objective:The moisture content in the soil directly affects the yield and quality of Panax notoginseng,especially at the age of three years old.However,the suitable moisture for the growth of P.notoginseng is unknown.In this study,the effects of different soil moisture on the growth of P.notoginseng were studied.Methods:Four different water treatments(0.45 field capacity(FC),0.60 FC, 0.70 FC, and 0.85 FC) were set up in Shilin County,Yunnan Province,China.The water consumption and daily dynamic of water consumption were determined daily(from April 21 to October 18,2012),and the daily dynamic of water consumption under different weather conditions(sunny and rainy) was determined.The transpiration coefficient and water use efficiency were calculated through dry matter accumulation and total water consumption.Accumulation of saponins of roots of P.notoginseng were analyzed by HPLC after treated,and the soil moisture content suitable for the growth of P.notoginseng was estimated by regression fitting of the active ingredient accumulation and the soil moisture content.Results:The water consumption of 0.85 FC,0.70 FC,0.60 FC and 0.45 FC were 2.89,3.68,3.37 and 2.73 kg/plant per day,respectively.The water consumption of P.notoginseng from June to August was greater than other months.The daily dynamic of water consumption on sunny days and sunny days after rain showed a "double peak" feature,and it showed a "single peak" feature on rainy days.The water uses efficiency(WUE) of 0.85 FC,0.70 FC,0.60 FC and 0.45 FC were 2.51,3.32,4.59,3.39 gDW/kg H_(2)O,respectively.The increase of soil moistu re content would reduce the WUE of P.notoginse ng.With the increase of soil water content,the content of notoginsenoside R_(1) and ginsenoside Rg_(1) did not change significantly,while the content of ginsenoside Rb_(1) and Rd showed a decreasing trend.Conclusion:Soil moisture content significantly affected the water consumption of P.notoginseng,and when it was 56.4% of the maximum water holding capacity in the field,the sum of the four saponins of 100 strains of P.notoginseng was the highest.

Transcriptional activity and subcellular location of SmWRKY42-like and its response to gibberellin and ethylene treatments in Salvia miltiorrhiza hairy roots

Objective: The exogenous gibberellin(GA) and ethylene(ET) treatment can improve the medicinal ingredients of Salvia miltiorrhiza. Interestingly, many reports pointed out that WRKY transcription factors played an important regulatory role in these treatment responses. However, whether the Sm WRKY mediate these treatment signalings in S. miltiorrhiza remains largely elusive.Methods: qRT-PCR was used for SmWRKY42-like in response to exogenous GA and ethephon(Eth) treatment. The subcellular location of SmWRKY42-like was transiently transformed into onion epidermal cells by particle bombardment. The self-activating activity of SmWRKY42-like was verified in AH109 yeast strain.Results: Sm WRKY42-like was a WRKY family gene in S. miltiorrhiza. The subcellular localization and transcriptional activity results of the SmWRKY42-like protein indicated that SmWRKY42-like mainly enriched in nucleus and might be a transcription factor in S. miltiorrhiza. In the meantime, the SmWRKY42-like gene significantly responded to exogenous GA and Eth treatment.Conclusion: These results collectively indicated the SmWRKY42-like gene functions, as an important hormone-responsive gene, might play a potentially role in ET and GA signaling pathways.