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Acetaldehyde-induced interleukin-1β and tumor necrosis factor-α production is inhibited by berberine through nuclear factor-κB signaling pathway in HepG2 cells

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Journal of Biomedical Science

Summary

Alcoholic liver disease (ALD) is one of the most common liver diseases in the world. Increased levels of proinflammatory cytokines, including interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), have been correlated with the patients affected by ALD. However, the direct effect of alcohol in the induction of IL-1β and TNF-α has not been clarified. In this study, we demonstrated that acetaldehyde, the metabolic product of ethanol, was able to induce IL-1β and TNF-α production in HepG2 cells. Nuclear factor-κB (NF-κB), the transcription factor involved in the regulation of cytokine production, was also activated by acetaldehyde through inhibitory κB-α (IκB-α) phosphorylation and degradation. However, the NF-κB inhibitors, such as aspirin, cyclosporin A and dexamethasone, inhibited both the acetaldehyde-induced NF-κB activity and the induced cytokine production. Therefore, these data suggested that acetaldehyde stimulated IL-1β and TNF-α production via the regulation of NF-κB 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-κB activity. Berberine, the major ingredient of these herbs, abolished acetaldehyde-induced NF-κB activity and cytokine production in a dose-dependent manner. Moreover, its inhibitory ability was through the inhibition of induced IκB-α phosphorylation and degradation. In conclusion, we first linked the acetaldehyde-induced NF-κB 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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Acknowledgements

This work was supported by grants from National Science Council and China Medical University, Taiwan, ROC.

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Authors and Affiliations

  1. Graduate Institute of Medical Science, China Medical University, Taichung 404, Taiwan

    Chien-Yun Hsiang & Shih-Lu Wu

  2. Molecular Biology Laboratory, Graduate Institute of Chinese Medical Science, China Medical University, 91 Hsueh-Shih Road, Taichung 404, Taiwan

    Shin-Ei Cheng & Tin-Yun Ho

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  1. Chien-Yun Hsiang
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Correspondence to Tin-Yun Ho.

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Hsiang, CY., Wu, SL., Cheng, SE. et al. Acetaldehyde-induced interleukin-1β and tumor necrosis factor-α production is inhibited by berberine through nuclear factor-κB signaling pathway in HepG2 cells. J Biomed Sci 12, 791–801 (2005). https://doi.org/10.1007/s11373-005-9003-4

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  • DOI: https://doi.org/10.1007/s11373-005-9003-4

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