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J Biomed Sci. 2005 Oct;12(5):791-801. Epub 2005 Nov 9.

Acetaldehyde-induced interleukin-1beta and tumor necrosis factor-alpha production is inhibited by berberine through nuclear factor-kappaB signaling pathway in HepG2 cells.

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1
Graduate Institute of Medical Science, China Medical University, Taichung 404, Taiwan. cyhsiang@mail.cmu.edu.tw

Abstract

Alcoholic liver disease (ALD) is one of the most common liver diseases in the world. Increased levels of proinflammatory cytokines, including interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha), have been correlated with the patients affected by ALD. However, the direct effect of alcohol in the induction of IL-1beta and TNF-alpha has not been clarified. In this study, we demonstrated that acetaldehyde, the metabolic product of ethanol, was able to induce IL-1beta and TNF-alpha production in HepG2 cells. Nuclear factor-kappaB (NF-kappaB), the transcription factor involved in the regulation of cytokine production, was also activated by acetaldehyde through inhibitory kappaB-alpha (IkappaB-alpha) phosphorylation and degradation. However, the NF-kappaB inhibitors, such as aspirin, cyclosporin A and dexamethasone, inhibited both the acetaldehyde-induced NF-kappaB activity and the induced cytokine production. Therefore, these data suggested that acetaldehyde stimulated IL-1beta and TNF-alpha production via the regulation of NF-kappaB signaling pathway. By screening 297 controlled Chinese medicinal herbs supervised by Committee on Chinese Medicine and Pharmacy at Taiwan, we found that Coptis chinensis (Huang-Lien) and Phellodendron amurense (Huang-Po) were capable of inhibiting acetaldehyde-induced NF-kappaB activity. Berberine, the major ingredient of these herbs, abolished acetaldehyde-induced NF-kappaB activity and cytokine production in a dose-dependent manner. Moreover, its inhibitory ability was through the inhibition of induced IkappaB-alpha phosphorylation and degradation. In conclusion, we first linked the acetaldehyde-induced NF-kappaB activity to the induced proinflammatory cytokine production in HepG2 cells. Our findings also suggested the potential role of berberine in the treatment of ALD.

PMID:
16132116
DOI:
10.1007/s11373-005-9003-4
[Indexed for MEDLINE]
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