Intervention effect and mechanism of breviscapine on hepatic fibrosis in rats
- VernacularTitle:灯盏花素对肝纤维化大鼠的干预作用及机制
- Author:
Dandan WEI
1
;
Shanshan LI
2
;
Minghao ZHANG
2
;
Yurun WEI
2
;
Hongling WANG
3
;
Shuangshuang CHAI
1
;
Jingjing YIN
1
;
Min ZHANG
1
;
Han ZHAO
4
;
Zongyao WU
5
;
Kuicheng ZHU
1
;
Qingbo WANG
1
Author Information
1. Dept. of Acupuncture and Moxibustion Pain,the First Affiliated Hospital of Henan University of Chinese Medicine,Zhengzhou 450099,China
2. Medical College,Henan University of Chinese Medicine,Zhengzhou 450046,China
3. Dept. of Oncology,the Third Affiliated Hospital of Henan University of Chinese Medicine,Zhengzhou 450006,China
4. Key Laboratory of Tibetan Medicine and Plateau Biology,University of Tibetan Medicine,Lhasa 850005,China
5. Experimental Animal Center,Zhengzhou University,Zhengzhou 450008,China
- Publication Type:Journal Article
- Keywords:
breviscapine;
hepatic fibrosis;
oxidative stress;
TGF-β1/Smad2/ERK1 pathway;
Keap1/Nrf2/HO-1 pathway
- From:
China Pharmacy
2024;35(6):671-677
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To investigate the intervention effect and potential mechanism of breviscapine on hepatic fibrosis (HF) in rats based on the transforming growth factor-β(1 TGF-β1)/Smad2/extracellular signal-regulated protein kinase 1(ERK1) and Kelch-like epichlorohydrin-associated protein 1(Keap1)/nuclear factor-erythroid 2-related factor 2(Nrf2)/heme oxygenase-1(HO-1) pathways. METHODS Totally 60 rats were randomly divided into normal control group, model group, breviscapine low-dose, medium-dose and high-dose groups (5.4, 10.8, 21.6 mg/kg), and colchicine group (positive control, 0.45 mg/kg), with 10 rats in each group, half male and half female. Except for the normal control group, HF model of the other groups was induced by carbon tetrachloride. Subsequently, each drug group was given corresponding medicine by gavage once a day for 28 days. The liver appearance of rats in each group was observed and their liver coefficients were calculated. The levels of alanineaminotransferase (ALT) and aspartate aminotransferase (AST)in serum, those of ALT, AST, superoxide dismutase (SOD),malondialdehyde (MDA) and glutathione peroxidase (GSH- Px) in liver tissue were detected. The liver tissue inflammatory and fibrotic changes were observed. The protein and mRNA expressions of TGF-β1, Smad2, ERK1, Nrf2, Keap1 and HO-in liver tissue were detected. RESULTS Compared with the normal control group, the model group showed large areas of white nodular lesions in the liver, obvious inflammatory cell infiltration and collagen fiber deposition. The body weight, the levels of SOD and GSH-Px in liver tissue, the protein and mRNA expressions of Nrf2 and HO-1 were significantly lowered in the model group (P<0.05); the liver coefficient, the percentage of Masson staining positive area, ALT and AST levels of serum and liver tissue, MDA level of liver tissue, the protein and mRNA expressions of TGF-β1, Smad2, ERK1 and Keap1 were significantly increased (P<0.05). Compared with the model group, the liver lesions of rats in each drug group were improved, and the above quantitative indexes were generally reversed (P<0.05). CONCLUSIONS Breviscapine has a good intervention effect on HF rats, which may be related to inhibiting TGF-β1/Smad2/ERK1 pathway for anti-fibrosis and regulating Keap1/Nrf2/HO-1 pathway to inhibit oxidative stress.