Xinhui citrus fermentation liquor ameliorates acute ulcerative colitis in mice via regulating intestinal bacteria homeostasis and Nrf2/NLRP3 pathway to repair intestinal mucosa
10.16438/j.0513-4870.2022-0704
- VernacularTitle:陈皮酵素调节肠菌稳态及Nrf2/NLRP3通路修复肠黏膜改善小鼠急性溃疡性结肠炎
- Author:
Li YUAN
1
;
Zhuo-shi LIAN
1
;
Liu-ting LUO
2
;
Bai-zhong CHEN
3
;
Zhi-bo ZHU
2
;
Jie ZHAO
4
Author Information
1. School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China
2. Clinical Research Center, TCM-Integrated Hospital of Southern Medical University, Guangzhou 510315, China
3. Guangdong Xinbaotang Biological Technology Co., Ltd., Jiangmen 529100, China
4. School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China; Clinical Research Center, TCM-Integrated Hospital of Southern Medical University, Guangzhou 510315, China
- Publication Type:Research Article
- Keywords:
italic>Xinhui citrus fermentation liquor;
ulcerative colitis;
gut microbiota;
italic>Akkermansia;
nuclear factor erythroid 2 related factor 2;
Nod-like receptor protein 3
- From:
Acta Pharmaceutica Sinica
2022;57(12):3513-3523
- CountryChina
- Language:Chinese
-
Abstract:
This study investigated the protective effect and related mechanisms of Xinhui citrus fermentation liquor on mice with ulcerative colitis. Animal experiments follow the rules of Animal Ethics Committee of Southern Medical University. C57BL/6 mice were given 3% dextran sodium sulfate (DSS) for 6 days to induce acute ulcerative colitis. During this period, Xinhui citrus fermentation liquor, decoction of Citrus reticulata blanco (both orally administrated with 300 mg·kg-1·d-1 crude polysaccharide) or positive drug 5-aminosalicylic acid (100 mg·kg-1·d-1) were gavaged continuously for 9 days. Cecal contents were collected for 16S rRNA sequencing analysis. The levels of inflammatory factors, tight junction proteins and nuclear factor erythroid 2 related factor 2 / Nod-like receptor protein 3 (Nrf2/NLRP3) pathway related proteins in the colon were detected by real-time PCR (RT-PCR), immunofluorescence and Western blot. Our results showed that Xinhui citrus fermentation liquor and Citrus reticulata blanco protected against UC-induced weight loss, diarrhea, bloody stool, and colon shortening. The mRNA and protein levels of pro-inflammatory factors, such as interleukin 6 (Il-6) and CXC chemokine ligand 10 (Cxcl10) and NLRP3 inflammasome were significantly decreased; the mRNA levels of colon anti-inflammatory factor (Il-10), tight junction protein [zonula occludens-1 (Zo-1), occludin, claudin-1], mucin 2 (Muc2), Nrf2, as well as the mRNA and protein levels of NAD(P)H quinine oxidoreductase 1 (NQO1) and heme oxygenase 1 (HO-1) were significantly increased. In addition, Xinhui citrus fermentation liquor increased the abundance of Akkermansia and reduced the abundance of harmful bacteria Enterococcus and Streptococcus. The correlation analysis showed that the abundance of Akkermansia was positively correlated with anti-inflammatory factors, tight junction protein and the related genes levels of Nrf2 signaling pathway. In summary, Xinhui citrus fermentation liquor ameliorates acute ulcerative colitis in mice via regulating intestinal bacteria homeostasis and Nrf2/NLRP3 pathway to repair intestinal mucosa.
