Cucurbitacin E Alleviates Colonic Barrier Function Impairment and Inflammation Response and Improves Microbial Composition on Experimental Colitis Models

Abstract

Fengxia Zhan,1 Wei Song,2 Yong Fan,3 Fangjian Wang,1 Qian Wang4,5 1Department of Clinical Laboratory, Hospital of Shandong University, Jinan, 250100, People’s Republic of China; 2Key Laboratory of Marine Eco-Environmental Science and Technology, First Institute of Oceanography, Ministry of Natural Resources, Qingdao, 266061, People’s Republic of China; 3Qingdao Mental Health Center, Qingdao University, Qingdao, People’s Republic of China; 4Department of Clinical Laboratory, Qilu Hospital, Shandong University, Jinan, 250012, People’s Republic of China; 5Department of Clinical Laboratory, Qilu Hospital (Qingdao), Shandong University, Qingdao, 266035, People’s Republic of ChinaCorrespondence: Qian Wang, Email [email protected]: Cucurbitacins, which are found in a variety of medicinal plants, vegetables and fruits, were known for their diverse pharmacological and biological activities, including anticancer, anti-oxidative and anti-inflammatory effects. Cucurbitacin E, one of the major cucurbitacins, was recently proved to inhibit inflammatory response.Methods: To explore the therapeutic effects of cucurbitacin E on colitis and the underlying mechanisms, male mice drunk water containing 2.5% dextran sulfate sodium (DSS) to establish colitis model and administrated with cucurbitacin E during and after DSS treatment. The disease activity index was scored and colonic histological damage was observed. Intestinal tight junction and inflammatory response were determined. 16S rRNA and transcriptome sequencing were performed to analyze gut microbiota composition and gene expression, respectively.Results: We found that cucurbitacin E alleviated DSS-induced body weight loss and impaired colonic morphology. Cucurbitacin E decreased the expression of inflammatory cytokines and cell apoptosis, and maintained barrier function. Additionally, cucurbitacin E retrieved DSS-induced alterations in the bacterial community composition. Furthermore, a variety of differentially expressed genes (DEGs) caused by cucurbitacin E were enriched in several pathways including the NFκB and TNF signaling pathways as well as in Th17 cell differentiation. There was a close relationship between DEGs and bacteria such as Escherichia-Shigella and Muribaculaceae.Conclusion: Our results revealed that cucurbitacin E may exert protective effects on colitis via modulating inflammatory response, microbiota composition and host gene expression. Our study supports the therapeutic potential of cucurbitacin E in colitis and indicates that gut microbes are potentially therapeutic targets.Keywords: barrier function, colitis, cucurbitacins, inflammation, microbiota

Keywords

• barrier function
• colitis
• cucurbitacins
• inflammation
• microbiota