Identification of Natural Compound Carnosol as a Novel TRPA1 Receptor Agonist
Chenxi Zhai,
Qing Liu,
Yuxin Zhang,
Shifeng Wang,
Yanling Zhang,
Shiyou Li,
Yanjiang Qiao
Affiliations
Chenxi Zhai
Key Laboratory of TCM-information Engineer of State Administration of TCM, School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China
Qing Liu
Key Laboratory of TCM-information Engineer of State Administration of TCM, School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China
Yuxin Zhang
Key Laboratory of TCM-information Engineer of State Administration of TCM, School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China
Shifeng Wang
Key Laboratory of TCM-information Engineer of State Administration of TCM, School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China
Yanling Zhang
Key Laboratory of TCM-information Engineer of State Administration of TCM, School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China
Shiyou Li
Laboratory of Genome Variations and Precision Bio-Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China
Yanjiang Qiao
Key Laboratory of TCM-information Engineer of State Administration of TCM, School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China
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.
