Next Article in Journal
Dimacrolide Sesquiterpene Pyridine Alkaloids from the Stems of Tripterygium regelii
Next Article in Special Issue
Anti-Inflammatory Chemical Profiling of the Australian Rainforest Tree Alphitonia petriei (Rhamnaceae)
Previous Article in Journal
In Vivo Targeted MR Imaging of Endogenous Neural Stem Cells in Ischemic Stroke
Previous Article in Special Issue
Neuroprotection by Combined Administration with Maslinic Acid, a Natural Product from Olea europaea, and MK-801 in the Cerebral Ischemia Model
Article Menu
Issue 9 (September) cover image

Export Article

Open AccessArticle
Molecules 2016, 21(9), 1145; doi:10.3390/molecules21091145

Cardamonin, a Novel Antagonist of hTRPA1 Cation Channel, Reveals Therapeutic Mechanism of Pathological Pain

1
Key Laboratory of TCM-Information Engineer of State Administration of TCM, School of Chinese Materia Medica, Beijing University of Chinese Medicine, No. 6 Wangjing Zhonghuan South Road, Chaoyang District, Beijing 100102, China
2
HD Biosciences, Co., Ltd., 590 Ruiqing Road, Zhangjiang Hi-Tech Park East Campus, Pudong New Area, Shanghai 201201, China
3
Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, No. 1 Beichen West Road, Chaoyang District, Beijing 100101, China
*
Authors to whom correspondence should be addressed.
Academic Editor: Peter Koulen
Received: 12 July 2016 / Revised: 25 August 2016 / Accepted: 25 August 2016 / Published: 29 August 2016
View Full-Text   |   Download PDF [2125 KB, uploaded 29 August 2016]   |  

Abstract

The increasing demand for safe and effective treatments of chronic pain has promoted the investigation of novel analgesic drugs. Some herbals have been known to be able to relieve pain, while the chemical basis and target involved in this process remained to be clarified. The current study aimed to find anti-nociceptive candidates targeting transient receptor potential ankyrin 1 (TRPA1), a receptor that implicates in hyperalgesia and neurogenic inflammation. In the current study, 156 chemicals were tested for blocking HEK293/TRPA1 ion channel by calcium-influx assay. Docking study was conducted to predict the binding modes of hit compound with TRPA1 using Discovery Studio. Cytotoxicity in HEK293 was conducted by Cell Titer-Glo assay. Additionally, cardiotoxicity was assessed via xCELLigence RTCA system. We uncovered that cardamonin selectively blocked TRPA1 activation while did not interact with TRPV1 nor TRPV4 channel. A concentration-dependent inhibitory effect was observed with IC50 of 454 nM. Docking analysis of cardamonin demonstrated a compatible interaction with A-967079-binding site of TRPA1. Meanwhile, cardamonin did not significantly reduce HEK293 cell viability, nor did it impair cardiomyocyte constriction. Our data suggest that cardamonin is a selective TRPA1 antagonist, providing novel insight into the target of its anti-nociceptive activity. View Full-Text
Keywords: Alpinia katsumadai hayata; cardamonin; TRPA1 antagonist; hyperalgeisa; cardiotoxicity Alpinia katsumadai hayata; cardamonin; TRPA1 antagonist; hyperalgeisa; cardiotoxicity
Figures

Figure 1a

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Wang, S.; Zhai, C.; Zhang, Y.; Yu, Y.; Zhang, Y.; Ma, L.; Li, S.; Qiao, Y. Cardamonin, a Novel Antagonist of hTRPA1 Cation Channel, Reveals Therapeutic Mechanism of Pathological Pain. Molecules 2016, 21, 1145.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]

Molecules EISSN 1420-3049 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top