Exploration of Effect and Mechanism of Poria Cocos on Chemotherapy Induced Intestinal Mucosal Inflammation in Mice Based on Network Pharmacology and Experimental Verification

TANG Yinbo; LIU Fuyu; SHAN Kaixin; FENG Yonggang; FAN Guoqi; MIAO Mingsan; FANG Xiaoyan

Abstract：Objective To observe the therapeutic effect of Poria Cocos on the intestinal mucosa of 5-fluorouracil(5-FU)-induced chemotherapeutic intestinal mucositis(CIM)model mice,and explore its possible mechanism in combination with network pharmacology.Methods The potential components and core targets of Poria Cocos were obtained by TCMSP database.Gene targets related to CIM were collected through GeneCards database,and Cytoscape3.7.2 was used to replace the data related to Poria Cocos to map the"drug-actives-target-disease"network.The Metascape database was substituted into the intersection target for GO enrichment analysis and KEGG pathway analysis.The mice were given prophylactic treatment with Poria Cocos for 5 days,followed by drug administration for 5 days,and the basic signs of the animals were recorded after treatment for 3 days.The pathological injury of ileum mucosa was observed by HE staining.The positive expression of nuclear factor(NF)-κB p65,cyclooxygenase(COX-2)and Occludin in intestinal mucosa of ileal tissue was observed by immunofluorescence staining.Results The results of network pharmacology showed that 14 active ingredients of Poria Cocos were selected by database and related literature,and 182 core targets of Poria Cocos for CIM were identified.The effect of Poria Cocos on CIM may be through cAMP signaling pathway and Toll-like receptor(TLR)signaling pathway.The results of animal experiments showed that compared with the model group,the body weight and food consumption,colon length and spleen index were increased in sulfasalazine and poria groups,and the differences were statistically significant(P<0.05).At the tissue level,the villi length of ileum in sulfasalazine group and Poria Cocos groups increased,the crypt depth of medium dose Poria Cocos group and sulfasalazine group decreased,and the goblet cell number increased significantly in sulfasalazine group and Poria Cocos groups,the difference was statistically significant(P<0.05).In terms of protein expression,the expression of NF-κB p65 and COX-2 in ileum of mice in medium and high dose groups and sulfasalazine group of Poria Cocos significantly decreased,and the expression of Occludin significantly increased,with statistical significance(P<0.01).Conclusion Poria Cocos has obvious therapeutic effect on 5-FU-induced CIM in mice,and its mechanism is related to inhibiting the expression of NF-κB p65 and COX-2 proteins in TLR pathway,increasing the expression of Occludin and improving immunity.