Polydatin Ameliorated Colonic Inflammation via Precluding Phosphorylation of PKCθ/STAT3 Pathway to Inhibit Th17 Cells in Mice with Ulcerative Colitis
10.13422/j.cnki.syfjx.20211739
- VernacularTitle:基于PKCθ/STAT3信号通路探讨虎杖苷抑制溃疡性结肠炎小鼠Th17细胞的效应
- Author:
Jia-jing LIU
1
;
Qiu-yi LI
1
;
Pei-guang MA
1
;
Yan-fei HONG
1
;
Dong-yu GE
1
;
Gui-ying PENG
1
;
Jun-xiang LI
2
Author Information
1. School of Life Sciences， Beijing University of Chinese Medicine， Beijing 100029， China
2. Dongfang Hospital， Beijing University of Chinese Medicine， Beijing 100078，China
- Publication Type:Research Article
- Keywords:
polydatin;
ulcerative colitis;
protein kinase Cθ（PKCθ）;
signal transducer and activator of transcription 3（STAT3）;
T helper cell 17（Th17）;
interleukin-17A（IL-17A）
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2021;27(17):40-45
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the therapeutic effect of polydatin on ulcerative colitis （UC） in mice and its regulation of protein kinase Cθ（PKCθ）/signal transducer and activator of transcription 3（STAT3） signaling on T helper cell 17（Th17） and its mechanism in the treatment of UC. Method:The 32 male C57BL/6 mice were randomly divided into normal group， model group， polydatin group （0.045 g·kg-1） and sulfasalazine group （0.5 g·kg-1）. The UC model was established by giving 3% dextran sodium sulfate （DSS） solution to free drinking water in mice. Polydatin and sulfasalazine groups were given by gavage 0.5 h before modeling for 7 days. The normal group and model group were given the same amount of normal saline. After the last administration， the colonic tissue was taken and hematoxylin-eosin （HE） was used to observe the pathological changes of colonic tissue. Flow cytometry was used to detect the proportion of Th17 in the lamina propria of colonic mucosa. The expression of interleukin-17A （IL-17A） in serum was detected by enzyme-linked immunosorbent assay （ELISA）. Polydatin was added to CD4+ T cells purified from spleen of C57BL/6 mice by magnetic-activated cell sorting （MACS） under the stimulation of cell stimulation cocktail in vitro in order to detect its impact on PKCθ and STAT3 phosphorylation. Result:Compared with normal group， the body weight was significantly decreased， and disease activity index （DAI） scores of the model group was significantly increased （P<0.01）， the colonic mucosal epithelium was damaged and inflammatory cells infiltration in the mucosa and submucosa was obvious， the proportion of Th17 in the lamina propria of colonic mucosa was significantly increased （P<0.01）， and the content of serum IL-17A was significantly increased （P<0.01）. Compared with the model group， the weight and DAI score of polydatin and sulfasalazine groups were significantly improved （P<0.01）， the degree of colon tissue damage was significantly improved， the proportion of Th17 in colon mucosa lamina propria was significantly decreased （P<0.01）， and the content of IL-17A in serum was significantly decreased （P<0.01）. In vitro experiments showed that polydatin could significantly inhibit the phosphorylation of PKCθ and STAT3 in Th17 （P<0.01） as well as IL-17A secretion. Conclusion:Polydatin can improve the ulcerative colitis in mice via inhibiting the phosphorylation of PKCθ and STAT3 to preclude IL-17A secreting in Th17.
