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  • Title: Effects of 13-alkyl-substituted berberine alkaloids on the expression of COX-II, TNF-alpha, iNOS, and IL-12 production in LPS-stimulated macrophages.
    Author: Lee DU, Kang YJ, Park MK, Lee YS, Seo HG, Kim TS, Kim CH, Chang KC.
    Journal: Life Sci; 2003 Aug 01; 73(11):1401-12. PubMed ID: 12850501.
    Abstract:
    Berberine, a major alkaloidal component of Coptidis Rhizoma, has antibacterial activity, anti-inflammatory effect, antitumor and antimotility actions. We suggested that one of possible mechanisms of anti-bacterial activity of berberine may be based on the production of interleukin (IL)-12. Recently 13-alkyl-substituted berberines were shown to be better activity than berberine against certain bacteria species and human cancer cell lines. In the present study, therefore, the effects of 13-methylberberine (13-MB) and 13-ethylberberine (13-EB) on the production of IL-12 and expression of iNOS, TNF-alpha and COX-II were investigated using macrophages in culture. In LPS-stimulated RAW 264.7 cells, these alkaloids decreased the nitrites, concentration-dependently. The concentration of 50% inhibition of NO production (IC50) by 13-MB and 13-EB was 11.64 and 9.32 microM, respectively. The suppressed expression of iNOS protein was responsible for the reduction of NO production. Neither the expression of mRNA of iNOS, COX-II and TNF- alpha nor protein of COX-II and TNF-alpha was affected by both 13-MB and 13-EB, but production of PGE2 in LPS-stimulated RAW 264.7 cells was significantly reduced. Another striking finding of the present study is that 13-MB and 13-EB increased production of IL-12 in LPS-treated splenic macrophages. These results indicate that posttranscriptional regulatory mechanism of iNOS gene expression by 13-MB and 13-EB is involved, and COX-II activity is inhibited by 13-MB and 13-EB, respectively. In conclusion, the present study demonstrates that 13-methyl- and 13-ethylberberine alkaloids can be useful as an immunotherapeutic compound for induction of IL-12, which is potentially applicable for tumors, infectious disease, and airway inflammation.
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