Effects of tanshinone ⅡA on TNBS-induced mouse model of chronic colitis through PXR/NF-κB signaling pathway
10.3969/j.issn.1001-1528.2025.04.010
- VernacularTitle:丹参酮ⅡA通过调控PXR/NF-κB信号通路对TNBS诱导小鼠慢性结肠炎的影响
- Author:
Shan-shan CHEN
1
;
Bing-bing SONG
;
Xian-qiong GONG
;
Jie ZHAO
;
Kai-qing ZHANG
;
Qiong WANG
Author Information
1. 南京中医药大学附属医院,江苏南京 210029;南京中医药大学第一临床医学院,江苏南京 210029
- Publication Type:Journal Article
- Keywords:
tanshinone ⅡA;
chronic colitis;
PXR-/-mice;
ZO-1;
Occludin;
PXR/NF-κB signaling pathway
- From:
Chinese Traditional Patent Medicine
2025;47(4):1129-1136
- CountryChina
- Language:Chinese
-
Abstract:
AIM To investigate the therapeutic mechanism of tanshinone ⅡA in a mouse model of chronic colitis induced by trinitrobenzene sulfonic acid(TNBS).METHODS The BALB/c mice were randomly divided into the control group,the model group,and the low-dose and high-dose tanshinone ⅡA groups(10,20 mg/kg).Chronic inflammatory bowel disease(IBD)was induced in the model and tanshinone ⅡA groups by epicutaneous application of 3.75 mg TNBS(dissolved in 48％ethanol),followed by intrarectal administration of TNBS(0.75,1.5 and 2.25 mg in 40％ethanol)on days 7,14 and 21.Starting on day 7 post-modeling,the mice underwent their 14-day consecutive dosing of corresponding drugs by gavage.The mice had their disease activity index(DAI)assessed;their colon length and weight measured;and their levels of inflammatory factors IFN-γ and TNF-α in the colon mucosa detected by ELISA.The wild-type and PXR-/-mice were randomly divided into the control group,the model group,and the tanshinone ⅡA group(20 mg/kg).After modeling and drug administration using the aforementioned method,Masson staining was used to assess the intestinal fibrosis;immunohistochemistry was employed to detect the colon expression of ZO-1 and Occludin proteins;and immunofluorescence was used to detect the colon expression of NF-κB p65.RESULTS Tanshinone ⅡA(20 mg/kg)reduced DAI scores,colon weight/length ratio,and the colon levels of IFN-γ and TNF-α of the mouse models(P＜0.05,P＜0.01).Compared with the WT control group,the WT model group and PXR-/-control group exhibited increased colon histopathological scores and fibrosis areas(P＜0.01),decreased protein expressions of ZO-1 and Occludin(P＜0.01),and increased expression of p-NF-κB p65(P＜0.01).Compared with the WT model group,the WT tanshinone ⅡA group showed reduced colon weight/length ratio,histopathological scores,and fibrosis areas(P＜0.01);increased protein expressions of ZO-1 and Occludin(P＜0.05,P＜0.01);and decreased expression of p-NF-κB p65(P＜0.01).However,tanshinone ⅡA showed no significant therapeutic effect upon PXR-/-model mice(P＞0.05).CONCLUSION Tanshinone ⅡA(20 mg/kg)can effectively alleviate TNBS-induced chronic colitis in mice,and this protective effect may be exerted by the modulation of PXR/NF-κB signaling pathway.
