title: Identification of natural compound carnosol as a novel TRPA1 receptor agonist.
abstract: The transient receptor potential ankyrin 1 (TRPA1) cation channel is one of the well-known targets for pain therapy. Herbal medicine is a rich source for new drugs and potentially useful therapeutic agents. To discover novel natural TRPA1 agonists, compounds isolated from Chinese herbs were screened using a cell-based calcium mobilization assay. Out of the 158 natural compounds derived from traditional Chinese herbal medicines, carnosol was identified as a novel agonist of TRPA1 with an EC50 value of 12.46 µM. And the agonistic effect of carnosol on TRPA1 could be blocked by A-967079, a selective TRPA1 antagonist. Furthermore, the specificity of carnosol was verified as it showed no significant effects on two other typical targets of TRP family member: TRPM8 and TRPV3. Carnosol exhibited anti-inflammatory and anti-nociceptive properties; the activation of TRPA1 might be responsible for the modulation of inflammatory nociceptive transmission. Collectively, our findings indicate that carnosol is a new anti-nociceptive agent targeting TRPA1 that can be used to explore further biological role in pain therapy.
authors.affiliation: Key Laboratory of TCM-information Engineer of State Administration of TCM, School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China. zhaichenxi1991@163.com.
authors.forename: Chenxi
authors.initials: C
authors.lastname: Zhai
authors.affiliation: Key Laboratory of TCM-information Engineer of State Administration of TCM, School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China. liuqingtcm@gmail.com.
authors.forename: Qing
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Key Laboratory of TCM-information Engineer of State Administration of TCM, School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China. zhangyuxinwjzy@163.com.
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Key Laboratory of TCM-information Engineer of State Administration of TCM, School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China. alana6268@126.com.
authors.forename: Shifeng
authors.initials: S
authors.lastname: Wang
authors.affiliation: Key Laboratory of TCM-information Engineer of State Administration of TCM, School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China. zhangyuxinwjzy@163.com.
authors.forename: Yanling
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Laboratory of Genome Variations and Precision Bio-Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China. lishiyou@big.ac.cn.
authors.forename: Shiyou
authors.initials: S
authors.lastname: Li
authors.affiliation: Key Laboratory of TCM-information Engineer of State Administration of TCM, School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China. yjqiao@263.net.
authors.forename: Yanjiang
authors.initials: Y
authors.lastname: Qiao
mesh_terms: D045784:Abietanes / Q000737:chemistry / Q000494:pharmacology; D000700:Analgesics / Q000737:chemistry / Q000494:pharmacology; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology; D015220:Calcium Channels / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D009419:Nerve Tissue Proteins / Q000819:agonists / Q000037:antagonists & inhibitors* / Q000235:genetics; D010091:Oximes / Q000494:pharmacology; D059408:Pain Management; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels / Q000819:agonists / Q000037:antagonists & inhibitors* / Q000235:genetics
chemical_list: C560402:A 967079; D045784:Abietanes; D000700:Analgesics; D000893:Anti-Inflammatory Agents; D015220:Calcium Channels; D009419:Nerve Tissue Proteins; D010091:Oximes; D000074025:TRPA1 Cation Channel; C473350:TRPA1 protein, human; D050051:Transient Receptor Potential Channels; C068623:carnosol