Journal
JOURNAL OF BIOMEDICAL SCIENCE
Volume 12, Issue 5, Pages 791-801Publisher
SPRINGER
DOI: 10.1007/s11373-005-9003-4
Keywords
acetaldehyde; alcoholic liver disease; berberine; cytokine; nuclear factor-kappa B
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Alcoholic liver disease (ALD) is one of the most common liver diseases in the world. Increased levels of proinflammatory cytokines, including interleukin-1 beta (IL-1 beta) 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-1 beta and TNF-alpha has not been clarified. In this study, we demonstrated that acetaldehyde, the metabolic product of ethanol, was able to induce IL-1 beta and TNF-alpha production in HepG2 cells. Nuclear factor-kappa B (NF-kappa B), the transcription factor involved in the regulation of cytokine production, was also activated by acetaldehyde through inhibitory kappa B-alpha (I kappa B-alpha) phosphorylation and degradation. However, the NF-kappa B inhibitors, such as aspirin, cyclosporin A and dexamethasone, inhibited both the acetaldehyde-induced NF-kappa B activity and the induced cytokine production. Therefore, these data suggested that acetaldehyde stimulated IL-1 beta and TNF-alpha production via the regulation of NF-kappa B 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-kappa B activity. Berberine, the major ingredient of these herbs, abolished acetaldehyde-induced NF-kappa B activity and cytokine production in a dose-dependent manner. Moreover, its inhibitory ability was through the inhibition of induced I kappa B-alpha phosphorylation and degradation. In conclusion, we first linked the acetaldehyde-induced NF-kappa B activity to the induced proinflammatory cytokine production in HepG2 cells. Our findings also suggested the potential role of berberine in the treatment of ALD.
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