Identification of 4 '-Demethyltangeretin as a Major Urinary Metabolite of Tangeretin in Mice and Its Anti-inflammatory Activities

文献类型： 外文期刊

第一作者： Guo, Shanshan

作者： Guo, Shanshan;Wu, Xian;Zheng, Jinkai;Dong, Ping;Xiao, Hang;Guo, Shanshan;Wu, Xian;Smith, Sarah A.;Zheng, Jinkai;Dong, Ping

作者机构：

关键词： tangeretin; 4 '-demethyltangeretin; biotransformation; metabolite; inflammation

期刊名称：JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY （ 影响因子：4.192； 五年影响因子：4.289 ）

ISSN： 0021-8561

年卷期： 2021 年 69 卷 15 期

页码：

收录情况： SCI

摘要： The present study showed that oral administration of tangeretin (TAN) in mice resulted in the production of 4'-demethyltangeretin (4DT) as a major urinary metabolite. The anti-inflammatory efficacy of TAN and 4DT was determined in RAW 264.7 macrophages stimulated by lipopolysaccharides (LPS). 4DT produced considerably stronger inhibition on the overproduction of prostaglandin E-2 and nitric oxide than TAN did at the same concentrations. Western blot and quantitative polymerase chain reaction analyses indicated that 4DT exerted more potent suppressive activity on the over-expression of interleukin-1 beta, inducible nitric oxide synthase, and cyclooxygenase-2 than TAN. Treatments with TAN and 4DT diminished LPS-stimulated nuclear factor kappa B (NF kappa B) translocation via suppressing the degradation of inhibitor kappa B (I kappa B alpha). Furthermore, both compounds attenuated mitogenactivated protein kinases (MAPKs) and Akt signaling upregulated by LPS. Overall, our findings showed that TAN and 4DT inhibited the LPS-stimulated inflammatory response in macrophages by suppressing Akt/MAPKs/NF kappa B proinflammatory pathways, while 4DT showed more potent activity than TAN, its parent compound.

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