基于网络药理学及肠道菌群探讨两色金鸡菊提取物对脾虚泄泻小鼠的影响OA

Objective:To explore the effect of Coreopsis tinctoria Nutt.extract on intestinal function in mice with spleen-deficiency diarrhea based on network pharmacology and gut microbiota analysis.Methods:Network pharmacology was used to predict the main signaling pathways and related targets of C.tinctoria in treating spleen-deficiency diarrhea.Molecular docking was conducted between active ingredients and pathway-related target proteins.The ethanol extract of C.tinctoria was prepared by reflux extraction using ethanol as a solvent and further purified using AB-8 macroporous ad-sorption resin.A mouse model of spleen-deficiency diarrhea was established through oral administration of rhubarb de-coction combined with a humid environment.The model mice were then randomly divided into a model control group,groups receiving purified ethanol extract of C.tinctoria at doses of 1.2,0.6,and 0.3g/kg,and a Lacidophilin tablet group.The normal control group and the model control group were given distilled water by gavage,while mice in the treatment groups received the corresponding drugs by gavage.The general physical signs and pathological changes in the colon tissue of mice were observed,and the serum cytokine levels were determined.The gut microbiota was analyzed u-sing the 16S gene sequencing method.The fecal short-chain fatty acid(SCFA)levels in mice were detected using 1H-NMR technology,and protein expression levels of colon mucosa were detected by Western blot.Results:Network phar-macology predicted that C.tinctoria mainly acted on the PI3K-Akt signaling pathway,cancer-related pathways,HIF-1 signaling pathway,cell apoptosis,and other pathways to manage spleen-deficiency diarrhea,involving 34 core targets.The purified ethanol extract increased the abundance and diversity of beneficial gut microbiota such as Bacteroidota,Muribac-ulaceae,Alistipes,and Roseburia,while decreasing the abundance of harmful gut microbiota such as Campilobacterota,Fir-micutes,Alloprevotella,and Erysipelatoclostridium.This regulation helped restore gut microbiota balance towards levels in normal control mice.The purified ethanol extract also reduced serum levels of IL-6,TNF-α,and VIP,as well as the ex-pression of AKT1,STAT3,and EGFR proteins in colon mucosa,while increasing serum levels of IL-10 and GAS in mice with spleen-deficiency diarrhea.Conclusion:The purified ethanol extract of C.tinctoria may prevent and mitigate the development of spleen-deficiency diarrhea in mice by regulating the gut microbiota balance,inhibiting serum and intesti-nal inflammation,downregulating the overexpression of AKT1,STAT3,and EGFR proteins in colon mucosal tissue,protec-ting and repairing intestinal mucosa,enhancing immune function,and modulating intestinal SCFA levels.