Physalin B attenuates liver fibrosis via suppressing LAP2α–HDAC1‐mediated deacetylation of the transcription factor GLI1 and hepatic stellate cell activation
Abstract
Background and purpose Liver fibrosis is one of the leading causes of morbidity and mortality worldwide but lacks any acceptable therapy. The transcription factor glioma-associated oncogene homologue 1 (GLI1) is a potentially important therapeutic target in liver fibrosis. This study investigates the anti-fibrotic activities and potential mechanisms of the phytochemical, physalin B. Experimental approach Two mouse models (CCl 4 challenge and bile duct ligation) were used to assess antifibrotic effects of physalin B in vivo. Mouse primary hepatic stellate cells (pHSCs) and human HSC line LX-2 also served as in vitro liver fibrosis models. Liver fibrogenic genes, GLI1 and GLI1 downstream genes were examined using Western blot and quantitative real-time PCR (qRT-PCR). GLI1 acetylation and LAP2α-HDAC1 interaction were analysed by co-immunoprecipitation. Key results In vivo, physalin B administration attenuated hepatic histopathological injury and collagen accumulation and decreased expression of fibrogenic genes. Physalin B dose-dependently suppressed fibrotic marker expression in LX-2 cells and mouse pHSCs. Mechanistic studies showed that physalin B inhibited GLI activity by non-canonical Hedgehog signalling. Physalin B blocked formation of lamina-associated polypeptide 2α (LAP2α)/histone deacetylase 1 (HDAC1) complexes, thus inhibiting HDAC1-mediated GLI1 deacetylation. Physalin B up-regulated acetylation of GLI1, down-regulated expression of GLI1 and subsequently inhibited HSC…
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Gli1 is a downstream effector of the Hh signaling pathway.
“Gli1 is a downstream effector of the Hh signaling pathway [30].”
From Saikosaponin b1 Attenuates Liver Fibrosis by Blocking STAT3/Gli1 Interaction and Inducing Gli1 Degradation (2025) · cites this paper as [30]
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- Authors
- Zhu, X., Ye, S., Yu, D., Zhang, Y., Li, J., Zhang, M., Leng, Y., Yang, T., Luo, J., Chen, X., Zhang, H., & Kong, L.
- Affiliations
- China Pharmaceutical University (CN)
- University of Electronic Science and Technology of China (CN)
- State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Bioactive Natural Product Research, School of Traditional Chinese Pharmacy China Pharmaceutical University Nanjing China
- Corresponding author
- Zhang, Hao
- Venue
- British Journal of Pharmacology
- Publisher
- Wiley
- Published
- 2021-05-21
- Volume
- 178
- Issue
- 17
- Pages
- 3428-3447
- ISSN
- 0007-1188 (ISSN-L)
- 1476-5381
- OpenAlex
- W3154517316
- Cited by
- 34
- References
- 5
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 12 · 2023: 4 · 2022: 1 · 2021: 3
- FWCI
- 2.78
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- British Journal of Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81872889, 82074068)
- Natural Science Foundation of Jiangsu Province (BK20181332)
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Keywords
- physalin B, liver fibrosis, Gli1, LAP2α, HDAC1, hepatic stellate cell activation, phytochemicals, antifibrotic agents, bile duct ligation, collagen deposition
- MeSH terms
- Zinc Finger Protein GLI1, Animals, Carbon Tetrachloride, Liver, Liver Cirrhosis, Secosteroids, Transcription Factors, Mice, Hedgehog Proteins, Hepatic Stellate Cells, Histone Deacetylase 1
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