Bear bile powder attenuates senecionine-induced hepatic sinusoidal obstruction syndrome in mice.
10.1016/S1875-5364(22)60169-9
- Author:
Kai-Yuan JIANG
1
,
2
;
Yi ZHANG
1
,
2
;
Xuan-Ling YE
3
;
Fen XIONG
3
;
Yan CHEN
3
;
Xia-Li JIA
3
;
Yi-Xin ZHANG
3
;
Li YANG
1
,
4
,
5
;
Ai-Zhen XIONG
1
,
6
;
Zheng-Tao WANG
1
,
2
Author Information
1. The MOE Key Laboratory for Standardization of Chinese Medicines and the SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
2. Shanghai R & D Center for Standardization of Traditional Chinese Medicines, Shanghai 201203, China.
3. The MOE Key Laboratory for Standardization of Chinese Medicines and the SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
4. Shanghai R & D Center for Standardization of Traditional Chinese Medicines, Shanghai 201203, China
5. Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address: yl7@shutcm.edu.cn.
6. Shanghai R & D Center for Standardization of Traditional Chinese Medicines, Shanghai 201203, China. Electronic address: aizhenxiong@shutcm.edu.cn.
- Publication Type:Journal Article
- Keywords:
Bear bile powder;
Bile acids;
Hepatic sinusoidal obstruction syndrome;
Liver disease;
Pyrrolizidine alkaloids
- MeSH:
Animals;
Bile;
Bile Acids and Salts;
Endothelial Cells/metabolism*;
Hepatic Veno-Occlusive Disease/pathology*;
Inflammation/pathology*;
Liver Cirrhosis/drug therapy*;
Mice;
Powders;
Pyrrolizidine Alkaloids/adverse effects*;
Ursidae
- From:
Chinese Journal of Natural Medicines (English Ed.)
2022;20(4):270-281
- CountryChina
- Language:English
-
Abstract:
Hepatic sinusoidal obstruction syndrome (HSOS) via exposure to pyrrolizidine alkaloids (PAs) is with high mortality and there is no effective treatment in clinics. Bear bile powder (BBP) is a famous traditional animal drug for curing a variety of hepatobiliary diseases such as cholestasis, inflammation, and fibrosis. Here, we aim to evaluate the protective effect of BBP against HSOS induced by senecionine, a highly hepatotoxic PA compound. Our results showed that BBP treatment protected mice from senecionine-induced HSOS dose-dependently, which was evident by improved liver histology including reduced infiltration of inflammatory cells and collagen positive cells, alleviated intrahepatic hemorrhage and hepatic sinusoidal endothelial cells, as well as decreased conventional serum liver function indicators. In addition, BBP treatment lowered matrix metalloproteinase 9 and pyrrole-protein adducts, two well-known markers positively associated with the severity of PA-induced HSOS. Further investigation showed that BBP treatment prevents the development of liver fibrosis by decreasing transforming growth factor beta and downstream fibrotic molecules. BBP treatment also alleviated senecionine-induced liver inflammation and lowered the pro-inflammatory cytokines, in which tauroursodeoxycholic acid played an important role. What's more, BBP treatment also decreased the accumulation of hydrophobic bile acids, such as cholic acid, taurocholic acid, glycocholic acid, as well. We concluded that BBP attenuates senecionine-induced HSOS in mice by repairing the bile acids homeostasis, preventing liver fibrosis, and alleviating liver inflammation. Our present study helps to pave the way to therapeutic approaches of the treatment of PA-induced liver injury in clinics.