Apple polyphenol extract alleviates DSS-induced ulcerative colitis and linked behavioral disorders via regulating the gut-brain axis

Abstract

To explore the effects of apple polyphenol extract (APE) on dextran sulfate sodium (DSS) induced acute ulcerative colitis (UC) and linked behavioral disorders, C57BL/6 male mice aged 9–11 weeks were randomly divided into the following groups: (1) Control group (CON), (2) 3% DSS group (DSS), (3) 3% DSS + APE at 8 a.m. group (DA-ZT0), (4) 3% DSS + APE at 8 p.m. group (DA-ZT12). APE was given at a dosage of 500 mg/(kg·bw·d). APE treatment elevated protein expressions of Occludin, zonula occludins-1 (ZO-1) and mucoprotein-2 (MUC2), and inhibited inflammatory response by down-regulating the (NOD)-like receptor family and pyrin domain containing 3 (NLRP3)/apoptosis-associated speck-like protein (ASC)/cysteine aspartate-specific protease-1 (caspase-1) signaling pathway. Meanwhile, APE alleviated anxiety and depression-like behavior disorders by upregulating brain-derived neurotrophic factor (BDNF) and postsynaptic-density protein 95 (PSD-95) and downregulating allograft inflammatory factor 1 (AIF1). Additionally, APE reshaped the structure of the intestinal microbiota, with an increased Firmicutes/Bacterodetes ratio and reduced the relative abundances of Escherichia-Shigella, Bacteroides and Parasutterella. Finally, APE reset DSS-induced circadian rhythm disturbance of clock genes, with significant induction of Cryptochrome2 (Cry2), Period2 (Per2) and Nuclear receptor subfamily 1 group D member 1 (Rev-erbα) in hippocampus and Brain and muscle arnt-like protein 1 (Bmal1) and Circadian locomotor output cycles kaput (Clock) in cortex in DA-ZT0 group, but APE treatment at ZT12 induced longer colon length, lower serum IL-β concentration and proteins expression of NLRP3 and ASC in colon, and better recovery of behavioral disorder. Thus, APE might conserve the potential as a diet-derived nutraceutical for UC treatment.