Effect of Modified Gegen Qinliantang on FXR/SHP/PPARα Signaling Pathway in Type 2 Diabetic db/db Mice
10.13422/j.cnki.syfjx.20231041
- VernacularTitle:加味葛根芩连汤对2型糖尿病db/db小鼠FXR/SHP/PPARα信号通路的影响
- Author:
Rong LIU
1
;
Jiahui WANG
2
;
Xia YANG
2
;
Yankui GAO
2
;
Miao LIU
2
;
Yonglin LIANG
2
;
Xiangdong ZHU
3
Author Information
1. School of Traditional Chinese Medicine(TCM), Jiangxi University of Chinese Medicine, Nanchang 330004, China
2. School of Basic Medicine, Gansu University of Chinese Medicine, Lanzhou 730000, China
3. School of TCM, Ningxia Medical University, Yinchuan 750000, China
- Publication Type:Journal Article
- Keywords:
type 2 diabetes mellitus;
modified Gegen Qinliantang;
farnesoid X receptor/small heterodimer partner/peroxisome proliferators-activated receptor α
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2023;29(20):1-8
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo observe the effect of modified Gegen Qinliantang on the expression levels of proteins related to the farnesoid X receptor/small heterodimer partner/peroxisome proliferator-activated receptor α (FXR/SHP/PPARα) signaling pathway in the liver tissue of db/db model mice with type 2 diabetes mellitus (T2DM) and explore the underlying mechanism of action of modified Gegen Qinliantang. MethodThirty db/db mice were randomly divided into model group, metformin group (0.2 g·kg-1), and high-, medium-, and low-dose modified Gegen Qinliantang groups (31.9, 19.1, 6.4 g·kg-1), with 6 mice in each group. An additional six m/m mice were assigned to the blank group. Respective drugs were administered via oral gavage for 12 weeks. Mouse body weight, fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) levels were measured. Oil red O staining was used to observe hepatic lipid accumulation and periodic acid-schiff (PAS) staining was used to assess hepatic glycogen deposition. Ammonium ferric sulfate staining was used to observe cholesterol deposition in intestinal tissues. Western blot was employed to detect the expression of FXR, cholesterol 7α-hydroxylase (CYP7A1), SHP, and PPARα proteins in liver tissues, and enzyme-linked immunosorbent assay (ELISA) was used to measure serum free fatty acid (FFA) levels. ResultAt the end of the treatment, compared with the blank group, the model group exhibited significant increases in mouse body weight, FBG, FFA, TC, TG, and LDL-C levels (P<0.01), along with significant hepatic lipid droplets, reduced hepatic glycogen, noticeable cholesterol accumulation in intestinal tissues, significantly decreased expression of FXR, SHP, PPARα proteins, and significantly increased expression of CYP7A1 protein in liver tissues (P<0.01). Compared with the model group, the metformin group and the high- and medium-dose modified Gegen Qinliantang groups demonstrated significant reductions in mouse body weight, FBG, FFA, TC, TG, LDL-C levels (P<0.05, P<0.01), significant increases in HDL-C levels (P<0.05, P<0.01), decreased hepatic lipid accumulation, increased hepatic glycogen, reduced intestinal cholesterol accumulation, significantly increased expression of FXR, SHP, PPARα proteins, and significantly decreased expression of CYP7A1 protein in liver tissues (P<0.01). ConclusionModified Gegen Qinliantang may regulate the FXR/SHP/PPARα signaling pathway to suppress FFA levels and improve lipid metabolism in T2DM mice.