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Nitidine Chloride Exerts Anti-Inflammatory Action by Targeting Topoisomerase I and Enhancing IL-10 Production

Nitidine Chloride Exerts Anti-Inflammatory Action by Targeting Topoisomerase I and Enhancing IL-10 Production

Niao Yang, Rongcai Yue, Jinzhu Ma, Wencai Li, Zeng Zhao, Huiliang Li, Yunheng Shen, Zhenlin Hu, Chao Lv, Xike Xu, Yili Yang, Xiankun Dai, Xia Liu, Yizhi Yu, Weidong Zhang

Pharmacol Res. 2019 Oct;148:104368.

PMID: 31415918

Abstract:

In the effort to identify natural products that regulate immunity and inflammation, we found that nitidine chloride (NC), an alkaloid from herb Zanthoxylum nitidum, enhanced IL-10 production in lipopolysaccharide (LPS)-stimulated myeloid cells. While NC was shown to be capable of inhibiting topoisomerase I (TOP1), NC analogs that could not inhibit TOP1 failed to increase IL-10 production. Moreover, medicinal TOP1 inhibitors TPT and SN-38 also augmented IL-10 production significantly, whereas knockdown of TOP1 prevented NC, TPT, and SN-38 from enhancing IL-10 expression. Thus, NC promoted IL-10 production by inhibiting TOP1. In LPS-induced endotoxemic mice, NC and TOP1 inhibitors increased IL-10 production, suppressed inflammatory responses, and reduced mortality remarkably. The anti-inflammatory activities of TOP1 inhibition were markedly reduced by IL-10-neutralizing antibody and largely absent in IL-10-deficient mice. In LPS-stimulated RAW264.7 cells and in peritoneal macrophages from endotoxemic mice, NC and TOP1 inhibitors significantly enhanced the activation of Akt, a critical signal transducer for IL-10 production, and inhibition of Akt prevented these compounds from enhancing IL-10 production and ameliorating endotoxemia. These data indicated that NC and TOP1 inhibitors are able to exert anti-inflammatory action through enhancing Akt-mediated IL-10 production and may assist with the treatment of inflammatory diseases.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP13063042	Nitidine chloride		13063-04-2	Price
AP3895929-B	Chelerythrine chloride		3895-92-9	Price

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