Recently, a selective TRPV3 antagonist has been identified by Ren Lai’s research group from Sino-Africa Joint Research Center, Kunming Institute of Zoology, Chinese Academy of Sciences. The research results were published in the British Journal of Pharmacology under the title 'A plant-derived TRPV3 inhibit or suppressing pain and itch'. (2021, 178(7):1669-1683), and has been applied for invention patent protection. Peter Muiruri Kamau, a PhD student from Kenya, is co-first author of the paper.

The transient receptor potential vanilloid 3 (TRPV3) channel is a promising target for treating pruritus. FlexStation and calcium fluorescence imaging were conducted to track the functional compounds. Whole-cell patch clamp was used torecord itch-related ion channel currents. Homologous recombination and site-directed mutagenesis were employed to construct TRPV3 channel chimeras and point mutations in order to explore the pharmacological mechanism. Mouse models were used for in vivo anti-pruritus assays. An acridone alkaloid (citrusinine-II) was purified and characterized from Atalantia monophylla. Citrusinine-II directly interacts with Y564 within the S4 helix of TRPV3 to selectively inhibit the channel with a half maximal inhibitory concentration (IC50) of 12.43 μM. Citrusinine-II showed potential efficacy to alleviate both chronic and acute itch. Intradermal administration of citrusinine-II (143ng/skin site) almost inhibited itching completely. It also showed significant analgesic effects. Little side effects of the compound have been observed. By acting as a selective and potent inhibitor of TRPV3 channel, citrusinine-II showed valuable therapeutic effects in pruritus animal models and is a promising candidate drug and/or lead molecule for the development of anti-pruritus drugs.

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