Shugan Heluo Xingpi Decoction inhibits liver fibrosis through regulation of Wnt/β-Catenin signaling pathway
10.3969/j.issn.1001-5256.2022.10.013
- VernacularTitle:舒肝和络醒脾方对肝纤维化模型大鼠肝组织Wnt/β-Catenin信号通路的影响
- Author:
Kuisong WANG
1
;
Qiuju ZHANG
2
;
Shuyao WEI
3
;
Shipeng YIN
4
;
Jieyu LI
1
;
Shiyu CHEN
1
;
Jiaqi GUO
1
;
Kunpeng ZHAO
1
Author Information
1. School of Clinical Medicine, Gansu University of Traditional Chinese Medicine, Lanzhou 730000, China
2. School of Basic Medicine, Gansu University of Traditional Chinese Medicine, Lanzhou 730000, China
3. School of Public Health, Gansu University of Traditional Chinese Medicine, Lanzhou 730000, China
4. Department of Ancient Books of Library, Gansu University of Traditional Chinese Medicine, Lanzhou 730000, China
- Publication Type:Original Article_Liver Fibrosis and Liver Cirrhosis
- Keywords:
Liver Cirrhosis;
Wnt Signaling Pathway;
Shugan Heluo Xingpi Decoction
- From:
Journal of Clinical Hepatology
2022;38(10):2265-2272
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the therapeutic effect of Shugan Heluo Xingpi Decoction on CCl 4 -induced liver fibrosis in rats, and the underlying molecular mechanism. Methods Sixty male SPF Wistar rats were randomly assigned to six groups: blank control, model, positive control, high, medium or low dose groups of Shugan Heluo Xingpi Decoction ( n =10 per group). The liver fibrosis rat model was induced by an intraperitoneal injection of 40% CCl 4 oil solution. Rats in the blank control and model groups were administered 10 mL/kg normal saline by gavage, rats in the positive control group were administered 50 mg/kg silibinin meglumine by gavage, while rats in high-dose, medium-dose and low-dose groups of Shugan Heluo Xingpi Decoction were administered 12.42 g/kg, 6.21 g/kg and 3.11 g/kg (crude drug/body weight) by gavage, respectively, daily for 8 weeks. Rats was sacrificed after 8 weeks, during which the physiological status of rats in each group was dynamically monitored. Following sacrifice, serum was collected to detect HYP using alkaline hydrolysis colorimetry and the expression levels of AST, ALT, total protein (TP), and Alb using an automatic biochemical analyzer. The pathological morphological changes in the liver were detected by H & E staining and Masson staining, and the mRNA and protein levels of Wnt1, β-Catenin and Cyclin D1 were detected by RT-qPCR and Western Blot. Measurement data were compared across groups using one-way ANOVA with post-hoc LSD- t test. Results Compared with the model group, after silibinin meglumine and Shugan Heluo Xingpi Decoction intervention, the physiological status of rats was significantly improved; serum levels of HYP, ALT, AST and Glo were significantly decreased, while serum levels of TP, Alb and A/G were significantly increased (all P < 0.05). Compared with the positive control group, serum levels of ALT and AST were significantly increased (all P < 0.05), while the levels of TP, Alb and A/G were significantly decreased (all P < 0.05) in low-dose group of Shugan Heluo Xingpi Decoction. H&E staining showed mild portal vein fibrosis with a few fibrous septa and mild steatosis of hepatocytes in the positive control group, obvious portal vein fibrosis with a few fiber septum in the low dose group, a few portal vein fibrosis in the medium dose group, while no obvious abnormality in the high dose group of Shugan Heluo Xingpi Decoction. Masson staining revealed that the therapeutic effect of high dose group of Shugan Heluo Xingpi Decoction on collagen deposition was superior to silibinin meglumine and medium and low dose of Shugan Heluo Xingpi Decoction (all P < 0.05), and was generally equivalent to high dose of Shugan Heluo Xingpi Decoction. Silibinin meglumine and medium and high doses of Shugan Heluo Xingpi Decoction inhibited more significantly the mRNA and protein expression of Wnt1, β-catenin and Cyclin D1 (all P < 0.05). Conclusion Shugan Heluo Xingpi Decoction shows anti-hepatic fibrosis effect, with a greater effect at higher doses. Regulating Wnt/β-Catenin signaling pathway may be one of the underlying molecular mechanisms.
