Effects of formononetin on the apoptosis of intestinal epithelial cells in rats with inflammatory bowel disease by regulating the Hippo/YAP signaling pathway
- VernacularTitle:芒柄花素调节Hippo/YAP信号通路对炎症性肠病大鼠肠上皮细胞凋亡的影响
- Author:
Dong XIE
1
;
Yuanyuan LIU
2
;
Zhengxiang LI
1
;
Hengjie YUAN
1
;
Xiaocang CAO
3
Author Information
1. Dept. of Pharmacy，Tianjin Medical University General Hospital，Tianjin 300052，China
2. Dept. of Genetics，School of Basic Medical Sciences，Tianjin Medical University，Tianjin 300070，China
3. Dept. of Gastroenterology，Tianjin Medical University General Hospital，Tianjin 300052，China
- Publication Type:Journal Article
- Keywords:
formononetin;
Hippo/YAP signaling pathway;
inflammatory bowel disease;
intestinal epithelial cells;
cell apoptosis
- From:
China Pharmacy
2024;35(13):1564-1569
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To investigate the effects of formononetin （FMN） on the apoptosis of intestinal epithelial cells in inflammatory bowel disease （IBD） rats and its possible mechanism. METHODS IBD rat model was constructed by using trinitrobenzene sulfonic acid （TNBS） induction. Forty-eight rats with successful modeling were divided into model group （normal saline）， low-dose and high-dose FMN groups （20 and 40 mg/kg FMN）， and high-dose FMN+YAP inhibitor Verteporfin （VTPF） group （40 mg/kg FMN+10 mg/kg VTPF）， with 12 rats in each group. Another 12 rats were set as the normal group （normal saline）. They were given drug/normal saline， once a day， for 7 consecutive days. After the last administration， the disease activity index （DAI） of rats was calculated， and the colon length of rats in each group was measured. The pathological changes in the colon tissue of rats were observed. The levels of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6） and IL-10 in serum were detected， and the apoptosis of intestinal epithelial cells was detected. The expressions of Yes associated protein （YAP）， cleaved cysteine-containing aspartate proteolytic enzyme 3 （cleaved-caspase-3）， B-cell lymphoma-2 （Bcl-2） and Bcl-2 associated X protein （Bax） were detected in colon tissue of rats. RESULTS Compared with the normal group， DAI score， the levels of TNF-α and IL- 6， the apoptotic rate of intestinal epithelial cells， and the expressions of cleaved-caspase-3 and Bax protein in the model group were increased greatly （P＜0.05）； the length of the colon was greatly decreased （P＜0.05）， and the serum level of IL-10 and the protein expressions of YAP and Bcl-2 were greatly reduced （P＜0.05）. The cell morphology of colon tissue was abnormal， with disordered arrangement and inflammatory cell infiltration. Compared with IBD group， the above indexes of rats were improved significantly in low-dose and high-dose FMN groups （P＜0.05）， in dose-dependent manner （P＜0.05）. VTPF significantly alleviated the effects of FMN on the above indexes of IBD rats （P＜0.05）. CONCLUSIONS FMN may promote the expression of YAP by inhibiting the Hippo/YAP signaling pathway， thereby inhibiting apoptosis of intestinal epithelial cells in IBD rats.
