Conflict of Interest: Nothing to report
Guggulsterone attenuates activation and survival of hepatic stellate cell by inhibiting nuclear factor kappa B activation and inducing apoptosis
Version of Record online: 22 NOV 2013
© 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd
Journal of Gastroenterology and Hepatology
Volume 28, Issue 12, pages 1859–1868, December 2013
How to Cite
Kim, B. H., Yoon, J.-H., Yang, J. I., Myung, S. J., Lee, J.-H., Jung, E. U., Yu, S. J., Kim, Y. J., Lee, H.-S. and Kim, C. Y. (2013), Guggulsterone attenuates activation and survival of hepatic stellate cell by inhibiting nuclear factor kappa B activation and inducing apoptosis. Journal of Gastroenterology and Hepatology, 28: 1859–1868. doi: 10.1111/jgh.12314
- Issue online: 22 NOV 2013
- Version of Record online: 22 NOV 2013
- Accepted manuscript online: 28 JUN 2013 05:54AM EST
- Manuscript Accepted: 29 MAY 2013
- hepatic stellate cell;
- liver fibrosis;
- nuclear factor kappa B
Background and Aim
Liver fibrosis is associated with the deposition of the extracellular matrix, and hepatic stellate cells (HSCs) are the major source of these matrix proteins. Guggulsterone has recently been shown to induce apoptosis in several cell lines. Thus, the aim of this study was to evaluate whether guggulsterone has antifibrotic activities by reducing the activation and survival of HSCs.
Apoptotic and fibrosis-related signaling pathways and nuclear factor kappa B (NF-κB) activity were explored in LX-2 cells, an immortalized human HSC line, and in a mice model of liver fibrosis.
Guggulsterone suppressed LX-2 cell growth in a dose- and activation-dependent manner. This growth suppression was due to the induction of HSC apoptosis, which was mediated by the activation of c-Jun N-terminal kinase and mitochondrial apoptotic signaling. Additionally, guggulsterone regulated phosphorylation of Akt and adenosine monophosphate-activated protein kinase, which were subsequently proven responsible for the guggulsterone-induced HSC growth suppression. Guggulsterone inhibited NF-κB activation in LX-2 cells, which is one of the major mediators in HSC activation. Indeed, guggulsterone decreased collagen α1 synthesis and α-smooth muscle actin expression in these cells. Compared with the control mice or mice treated with a low dose of guggulsterone, high dose of guggulsterone significantly decreased the extent of collagen deposition and the percentage of activated HSCs undergoing apoptosis.
These results demonstrate that guggulsterone suppressed HSC activation and survival by inhibiting NF-κB activation and inducing apoptosis. Therefore, guggulsterone may be useful as an antifibrotic agent in chronic liver diseases.