GABA A receptors as in vivo substrate for the anxiolytic action of valerenic acid, a major constituent of valerian root extracts
- PMID: 18602406
- DOI: 10.1016/j.neuropharm.2008.06.013
GABA A receptors as in vivo substrate for the anxiolytic action of valerenic acid, a major constituent of valerian root extracts
Abstract
Valerian extracts have been used for centuries to alleviate restlessness and anxiety albeit with unknown mechanism of action in vivo. We now describe a specific binding site on GABA(A) receptors with nM affinity for valerenic acid and valerenol, common constituents of valerian. Both agents enhanced the response to GABA at multiple types of recombinant GABA(A) receptors. A point mutation in the beta2 or beta3 subunit (N265M) of recombinant receptors strongly reduced the drug response. In vivo, valerenic acid and valerenol exerted anxiolytic activity with high potencies in the elevated plus maze and the light/dark choice test in wild type mice. In beta3 (N265M) point-mutated mice the anxiolytic activity of valerenic acid was absent. Thus, neurons expressing beta3 containing GABA(A) receptors are a major cellular substrate for the anxiolytic action of valerian extracts.
Similar articles
-
The anxiolytic effects of a Valerian extract is based on valerenic acid.BMC Complement Altern Med. 2014 Jul 28;14:267. doi: 10.1186/1472-6882-14-267. BMC Complement Altern Med. 2014. PMID: 25066015 Free PMC article.
-
Valerenic acid potentiates and inhibits GABA(A) receptors: molecular mechanism and subunit specificity.Neuropharmacology. 2007 Jul;53(1):178-87. doi: 10.1016/j.neuropharm.2007.04.018. Epub 2007 May 13. Neuropharmacology. 2007. PMID: 17585957
-
Valerian extract characterized by high valerenic acid and low acetoxy valerenic acid contents demonstrates anxiolytic activity.Phytomedicine. 2012 Oct 15;19(13):1216-22. doi: 10.1016/j.phymed.2012.08.003. Epub 2012 Sep 1. Phytomedicine. 2012. PMID: 22944521
-
The genetic basis of the pharmacological effects of anxiolytics: a review based on rodent models.Behav Pharmacol. 2001 Nov;12(6-7):451-60. doi: 10.1097/00008877-200111000-00005. Behav Pharmacol. 2001. PMID: 11742138 Review.
-
Mechanism of action of anxiolytic drugs.Prog Drug Res. 1987;31:315-47. doi: 10.1007/978-3-0348-9289-6_10. Prog Drug Res. 1987. PMID: 2894040 Review. No abstract available.
Cited by 26 articles
-
Acute and subacute toxicity of Ammi visnaga on rats.Interdiscip Toxicol. 2019 Sep;12(1):26-35. doi: 10.2478/intox-2019-0004. Epub 2020 Feb 20. Interdiscip Toxicol. 2019. PMID: 32189984 Free PMC article.
-
Natural Compounds for the Management of Parkinson's Disease and Attention-Deficit/Hyperactivity Disorder.Biomed Res Int. 2018 Nov 22;2018:4067597. doi: 10.1155/2018/4067597. eCollection 2018. Biomed Res Int. 2018. PMID: 30596091 Free PMC article. Review.
-
The roles of valerenic acid on BDNF expression in the SH-SY5Y cell.Saudi Pharm J. 2018 Nov;26(7):960-964. doi: 10.1016/j.jsps.2018.05.005. Epub 2018 Jun 8. Saudi Pharm J. 2018. PMID: 30416353 Free PMC article.
-
An Emerging Circuit Pharmacology of GABAA Receptors.Trends Pharmacol Sci. 2018 Aug;39(8):710-732. doi: 10.1016/j.tips.2018.04.003. Epub 2018 Jun 11. Trends Pharmacol Sci. 2018. PMID: 29903580 Free PMC article. Review.
-
Anesthetic Agents of Plant Origin: A Review of Phytochemicals with Anesthetic Activity.Molecules. 2017 Aug 18;22(8):1369. doi: 10.3390/molecules22081369. Molecules. 2017. PMID: 28820497 Free PMC article. Review.
MeSH terms
Substances
LinkOut - more resources
-
Full Text Sources
-
Other Literature Sources
