Effects of 4-hydroxy-2（3H）-benzoxazolone on Inflammatory and Apoptosis Signaling Pathways in Non-alcoholic Fatty Liver Disease Model Rats
- VernacularTitle:4-羟基-苯丙噁唑-2-酮对非酒精性脂肪肝病模型大鼠炎症和凋亡信号通路的影响
- Author:
Wanpeng XU
1
;
Jun LIN
1
;
Yingqin LIANG
1
;
Huanfang ZHOU
1
;
Hua ZHANG
1
;
Shizhen HUANG
2
;
Xuemei SUN
1
;
Xiugui WEI
3
;
Hongyuan WANG
1
;
Lin LIU
1
Author Information
1. School of Pharmacy，Guangxi Medical University，Guangxi 530021
2. Neurosurgery Department，the Second People’s Hospital of Nanning，Guangxi 530031
3. Pharmacy Department，the First People’s Hospital of Nanning，Guangxi 530022
- Publication Type:Journal Article
- Keywords:
4-hydroxy-2（3H）-benzoxazolone;
Non-alcoholic fatty liver disease;
Inflammation;
Apoptosis;
TLR4/MyD88/NF-
- From:
China Pharmacy
2021;32(11):1298-1303
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE：To inv estigate the effects of 4-hydroxy-2（3H）-benzoxazolone on inflammatory and apoptosis signaling pathways in non-alcoholic fatty liver disease （NAFLD）model rats. METHODS ：SD rats were divided into normal control group（10 rats）and modeling group （50 rats）. Normal control group was given basic diet ，and modeling group were given high-fat diet to induce NAFLD model. After modeling ，the rats were divided into normal control group ，model group ，silibinin group （26.25 mg/kg），and 4-hydroxy-2（3H）-benzoxazolone high-dose ，medium-dose and low-dose groups （100，50，25 mg/kg），with 8 rats in each group. Normal control group and modeling group were given 0.6％ CMC-Na intragastrically ，and other groups were given relevant medicine 10 mL/kg intragastrically ，once a day ，for consecutive 4 weeks. After last medication ，the serum levels of albumin（ALB），total protein （TP），globulin（GLB），ALB/GLB and free fatty acid （FFA）were detected ；TUNEL staining was used to observe the apoptosis of rat hepatocytes. Western blot assay was used to detect the protein expression and phosphorylation level of inflammatory signaling pathway related proteins [Toll-like receptor 4（TLR4），myeloid differentiation factor 88（MyD88）， nuclear factor-κB p65（NF-κB p65），NF-κB inhibitor protein（IκBα）] in liver tissue as well as the expression of apoptosis signaling pathway related proteins [B cell lymphoma 2（Bcl-2），Bax，caspase-3]. RESULTS ：Compared with model group ，serum levels of TP （except for low-dose group ），GLB and FFA ，the protein expression of TLR 4（except for low-dose group ），MyD88 （except for medium-dose group ）and caspase- 3，the phosphorylation levels of NF-κB p65 and IκBα protein were decreased significantly（P＜0.05 or P＜0.01）. The ratio of A LB/GLB in serum and the ratio of Bcl- 2/Bax in liver tissue were significantly increased（P＜0.05 or P＜0.01），and the phenomenon of hepatocyte apoptosis was improved. CONCLUSIONS ：4-hydroxy-2 （3H）-benzoxazolone can ameliorate NAFLD in rats ，and the mechanism may be associated with inhibiting the expression TLR 4/ MyD88/NF-κB signaling pathway-related proteins and apoptosis-related proteins in liver tissues.
