A plant-derived TRPV3 inhibitor suppresses pain and itch

	A plant-derived TRPV3 inhibitor suppresses pain and itch
	Han, YL; Luo, AN; Kamau, PM; Takomthong, P; Hu, JM; Boonyarat, C; Luo, L; Lai, R
	2021
发表期刊	BRITISH JOURNAL OF PHARMACOLOGY
ISSN	0007-1188
卷号	178 期号:7 页码:1669-1683
摘要	Background and Purpose Itching is the most frequent pathology in dermatology that has significant impacts on people's mental health and social life. Transient receptor potential vanilloid 3 (TRPV3) channel is a promising target for treating pruritus. However, few selecetive and potent antagonists have been reported. This study was designed to identify selective TRPV3 antagonist and elucidate its anti-pruritus pharmacology. Experimental Approach FlexStation and calcium fluorescence imaging were conducted to track the functional compounds. Whole-cell patch clamp was used to record itch-related ion channel currents. Homologous recombination and site-directed mutagenesis were employed to construct TRPV3 channel chimeras and point mutations for exploring pharmacological mechanism. Mouse models were used for in vivo anti-pruritus assay. Key Results An acridone alkaloid (citrusinine-II) was purified and characterized from Atalantia monophylla. It directly interacts with Y564 within S4 helix of TRPV3 to selectively inhibit the channel with a half maximal inhibitory concentration (IC50) of 12.43 mu M. Citrusinine-II showed potential efficacy to attenuate both chronic and acute itch. Intradermal administration of citrusinine-II (143 ng/skin site) nearly completely inhibited itch behaviours. It also shows significant analgesic effects. Little side effects of the compound are observed. Conclusion and Implications By acting as a selective and potent inhibitor of TRPV3 channel, citrusinine-II shows valuable therapeutic effects in pruritus animal models and is a promising candidate drug and/or lead molecule for the development of anti-pruritus drugs.
收录类别	sci
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/13216
专题	科研部门_天然药物功能蛋白质学科组（赖仞）
推荐引用方式 GB/T 7714	Han, YL,Luo, AN,Kamau, PM,et al. A plant-derived TRPV3 inhibitor suppresses pain and itch[J]. BRITISH JOURNAL OF PHARMACOLOGY,2021,178(7):1669-1683.
APA	Han, YL.,Luo, AN.,Kamau, PM.,Takomthong, P.,Hu, JM.,...&Lai, R.(2021).A plant-derived TRPV3 inhibitor suppresses pain and itch.BRITISH JOURNAL OF PHARMACOLOGY,178(7),1669-1683.
MLA	Han, YL,et al."A plant-derived TRPV3 inhibitor suppresses pain and itch".BRITISH JOURNAL OF PHARMACOLOGY 178.7(2021):1669-1683.

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