Apple Polyphenols Extract (APE) Alleviated Dextran Sulfate Sodium Induced Acute Ulcerative Colitis and Accompanying Neuroinflammation via Inhibition of Apoptosis and Pyroptosis.

Fang Liu,Yan Yin,Dong Qiu,Shilan Li,Xinjing Wang,Xinli Li,Yuan Cui

doi:10.3390/foods10112711

Abstract

The main aim of this study was to investigate the potent anti-apoptosis and anti-pyroptosis effects of apple polyphenols extract (APE) on dextran sulfate sodium model group (DSS)-induced acute ulcerative colitis (UC) and the protective effect of APE against acute UC-related neuroinflammation and synapse damage. Forty-three C57BL/6 male mice were randomly divided into a control group (CON), a 3% DSS model group (DSS), a 500 mg/(kg·bw·d) APE group (HAP), and a 125 (LD) or 500 (HD) mg/(kg·bw·d) APE treatment concomitantly with DSS treatment group. The results showed that APE significantly ameliorated DSS-induced acute UC through inhibiting intestinal epithelial cell (IEC) apoptosis and the Caspase-1/Caspase-11-dependent pyroptosis pathway, with increased BCL-2 protein expression and decreased protein levels of NLRP3, ASC, Caspase-1/11, and GSDND. Furthermore, APE significantly reduced acute UC-related neuroinflammation and synapse damage, supported by decreased mRNA levels of hypothalamus Cox-2 and hippocampus Gfap and also increased the mRNA levels of hypothalamus Psd-95. The increased protein expression of ZO-1 and Occludin improved the intestinal barrier integrity and improved the function of goblet cells by upregulating the protein level of MUC-2 and TTF3 accounted for the beneficial effects of APE on UC-associated neuroinflammation. Therefore, APE might be a safe and effective agent for the management of acute UC.

Highlights

Ulcerative colitis (UC) is a kind of metabolic disorder whose characteristics are diarrhea, mucus pus, bloody stools, and abdominal pain [1]
Mice treated with 3% dextran sulfate sodium model group (DSS) presented obviously increased disease activity index (DAI) scores, while a high dose of apple polyphenols extract (APE) intervention showed a protective effect against DSS-caused DAI score increase (Figure 2A)
Our results reflected that the role of APE in protecting intestinal barrier integrity might be associated with its regulation of MUC-2 and trefoil factor 3 (TFF3) secretion

Summary

Introduction

Ulcerative colitis (UC) is a kind of metabolic disorder whose characteristics are diarrhea, mucus pus, bloody stools, and abdominal pain [1]. The incidence of UC has reached a plateau in developed countries but increased in developing countries due to economic development and the uptake of a Westernized diet [2,3,4,5]. Statistical data have shown that the global incidence and prevalence of UC were 1.2–20.3/100,000 and 7.6–245/100,000, respectively [6]. Despite the precise etiology of UC remaining unknown, studies have shown that excessive intestinal epithelial cell (IEC) apoptosis, which is a cell death modality, plays a key pathogenic role [9,10]. The enhanced apoptosis of IEC disrupts epithelial barrier function [11], which might result in harmful substances in the intestines infiltrating into other tissues, organs, and the blood circulation [12], thereby increasing the risk of UC

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