Cultured bear bile powder ameliorates acute liver injury in cholestatic mice via inhibition of hepatic inflammation and apoptosis

Jingyi Cai; Jiasheng Wu; Su Fang; Shaoyong Liu; Tianming Wang; Yuanyuan Li; Juan Zou; Rong Shi; Zhengtao Wang; Li Yang; Yueming Ma

doi:10.1016/j.jep.2021.114829

Cultured bear bile powder ameliorates acute liver injury in cholestatic mice via inhibition of hepatic inflammation and apoptosis

J Ethnopharmacol. 2022 Feb 10:284:114829. doi: 10.1016/j.jep.2021.114829. Epub 2021 Nov 8.

Authors

Jingyi Cai¹, Jiasheng Wu¹, Su Fang¹, Shaoyong Liu², Tianming Wang¹, Yuanyuan Li¹, Juan Zou¹, Rong Shi¹, Zhengtao Wang³, Li Yang⁴, Yueming Ma⁵

Affiliations

¹ Department of Pharmacology, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
² Shanghai Kai Bao Pharmaceutical CO. Ltd., Shanghai, 201401, China.
³ Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
⁴ Center for Traditional Chinese Medicine of Complexity Systems, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. Electronic address: yl7@shutcm.edu.cn.
⁵ Department of Pharmacology, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; Shanghai Key Laboratory of Compound Chinese Medicines, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. Electronic address: mayueming@shutcm.edu.cn.

PMID: 34763041
DOI: 10.1016/j.jep.2021.114829

Abstract

Ethnopharmacological relevance: Natural bear bile powder (NBBP) is a traditional Chinese medicine used for treating liver dysfunction. Cultured bear bile powder (CBBP), which is produced using biotransformation of chicken bile, acts as an appropriate substitute for NBBP when treating cholestatic liver injury.

Aim of the study: To investigate the molecular mechanisms underlying the hepatoprotective effects of CBBP in an α-naphthylisothiocyanate (ANIT)-induced cholestatic mouse model.

Materials and methods: Cholestatic mice were pretreated with CBBP or NBBP via oral gavage once a day for two weeks. Their blood biochemistry and liver histopathology were then evaluated using standard protocols. Western blot analyses, real-time polymerase chain reaction, and immunohistochemistry were used to evaluate changes in the protein levels and gene expression profiles of factors associated with hepatic inflammation and apoptosis in cholestatic mice.

Results: CBBP significantly decreased the serum indices of liver injury, and ameliorated neutrophil infiltration and hepatocyte necrosis within liver tissue of cholestatic mice. Expression of the inflammatory factors, such as tumor necrosis factor-α, interleukin-1β (IL-1β), IL-6, monocyte chemoattractant protein-1, and intercellular adhesion molecule 1, was significantly reduced in CBBP-treated cholestatic mice. Moreover, proteins involved in the toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-kappa B (TLR4/Myd88/NF-κB) signaling pathway, such as CD14, TLR4, Myd88, and NF-κB, that were increased in cholestatic mice, were downregulated by CBBP. Meanwhile, increased expression of the apoptosis-related proteins, caspase-3 and Bax, in cholestatic mice was reversed by CBBP treatment.

Conclusion: CBBP treatment alleviates ANIT-induced cholestasis and liver injury by reducing hepatocyte inflammation and apoptosis.

Keywords: Apoptosis; Cholestasis; Cultured bear bile powder; Inflammation; Liver injury; Natural bear bile powder.

MeSH terms

1-Naphthylisothiocyanate / toxicity
Animals
Apoptosis / drug effects
Bile*
Chickens
Cholestasis / chemically induced*
Cholestasis / drug therapy*
Inflammation / drug therapy*
Male
Medicine, Chinese Traditional
Medicine, East Asian Traditional
Mice
Mice, Inbred C57BL
Powders*
Random Allocation
Ursidae*

Substances

Powders
1-Naphthylisothiocyanate