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首页> 外文期刊>Life sciences >Effects of 13-alkyl-substituted berberine alkaloids on the expression of COX-II, TNF-alpha, iNOS, and IL-12 production in LPS-stimulated macrophages.
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Effects of 13-alkyl-substituted berberine alkaloids on the expression of COX-II, TNF-alpha, iNOS, and IL-12 production in LPS-stimulated macrophages.

机译：13烷基取代的小ber碱生物碱对LPS刺激的巨噬细胞中COX-II，TNF-α，iNOS和IL-12产生的表达的影响。

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摘要

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.
机译：小ber碱是黄连的主要生物碱成分，具有抗菌活性，抗炎作用，抗肿瘤和抗运动作用。我们建议，小ber碱抗菌活性的可能机制之一可能是基于白介素（IL）-12的产生。最近，13-烷基取代的小ber碱对某些细菌和人类癌细胞系的活性优于小ber碱。因此，在本研究中，使用巨噬细胞研究了13-甲基小ber碱（13-MB）和13-乙基小ber碱（13-EB）对IL-12产生以及iNOS，TNF-α和COX-II表达的影响。在文化中。在LPS刺激的RAW 264.7细胞中，这些生物碱浓度依赖性地降低了亚硝酸盐。 13 MB和13-EB对NO产生（IC50）的50％抑制浓度分别为11.64和9.32 microM。 iNOS蛋白表达的抑制是NO产生减少的原因。 iNOS，COX-II和TNF-α的mRNA表达或COX-II和TNF-α的蛋白均不受13-MB和13-EB的影响，但是LPS刺激的RAW 264.7细胞中PGE2的产生显着减少。本研究的另一个惊人发现是13-MB和13-EB增加了LPS处理的脾巨噬细胞中IL-12的产生。这些结果表明，涉及13-MB和13-EB的iNOS基因表达的转录后调控机制，而COX-II活性分别被13-MB和13-EB抑制。总之，本研究证明13-甲基和13-乙基小ber碱生物碱可用作诱导IL-12的免疫治疗化合物，其可能适用于肿瘤，传染病和气道炎症。

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