Nakamura Toshiyuki, Miyoshi Noriyuki, Ishii Takeshi, Nishikawa Miyu, Ikushiro Shinichi, Watanabe Tatsuo
a School of Food and Nutritional Sciences , University of Shizuoka , Shizuoka , Japan.
b Laboratory of Food & Nutritional Sciences, Faculty of Nutrition , Kobe Gakuin University , Kobe , Japan.
Biosci Biotechnol Biochem. 2016 May;80(5):949-54. doi: 10.1080/09168451.2015.1132148. Epub 2016 Jan 25.
The agonistic activity of quercetin and its analogs towards the transient receptor potential ankyrin 1 (TRPA1) has been experimentally investigated. The human TRPA1 was expressed in HEK293T cells using a tetracycline-inducible system. The activation of TRPA1 was evaluated by a fluo-4 fluorescence assay based on calcium sensing. The results of a structure-activity relationship study led to the selection of six flavonoids, all of which activated the TRPA1 channel in a dose-dependent manner. Notably, the activation of TRPA1 by these flavonoid aglycones was completely inhibited by the co-treatment of the HEK293T cells with the TRPA1-specific antagonist, HC-030031. Several flavonoid glycosides and metabolites were also evaluated, but did not activate the TRPA1 except for methylated quercetin. On the other hand, TRPV1 (vanilloid receptor) did not respond to any of the flavonoids evaluated in this study. Therefore, these data suggest that the flavonoids would be promising ligands for the TRPA1.
槲皮素及其类似物对瞬时受体电位锚蛋白1（TRPA1）的激动活性已通过实验进行了研究。使用四环素诱导系统在HEK293T细胞中表达人TRPA1。基于钙传感的fluo-4荧光测定法评估TRPA1的激活情况。构效关系研究的结果导致选择了六种黄酮类化合物，所有这些化合物均以剂量依赖性方式激活TRPA1通道。值得注意的是，用TRPA1特异性拮抗剂HC-030031共同处理HEK293T细胞可完全抑制这些黄酮苷元对TRPA1的激活。还评估了几种黄酮苷和代谢物，但除甲基化槲皮素外，均未激活TRPA1。另一方面，TRPV1（香草酸受体）对本研究中评估的任何黄酮类化合物均无反应。因此，这些数据表明黄酮类化合物可能是TRPA1的有前景的配体。
