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

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 center dot bw center dot 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 (caspase1) 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-erb alpha) 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-beta 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.

Automated summary

The effects of apple polyphenol extract (APE) on DSS-induced UC and behavioral disorders were explored. APE treatment improved symptoms of UC and behavioral disorders by regulating signaling pathways and intestinal microbiota. These findings suggest that APE has potential as a treatment for UC.