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The precise mechanism of this action has not been established. It is likely that several different components of the plant contribute to the effect. Valerenic acid is thought to be at least partly responsible for the sedative effects.
A study in 2004 found valerenic acid to act as a subtype-selective GABAA receptor positive allosteric modulator in neonatal rat brainstem preparations. The mechanism of this action could not be elucidated in this study.
A study in 2007 on GABA receptors of various composition, expressed in Xenopus oocytes (frog eggs), found valerenic acid to act mainly at α1β2 and α1β3 subtypes of these receptors. Only channels incorporating β2 or β3 subunits were stimulated by valerenic acid. Modulation of ion channel action was not significantly dependent on incorporation of α1, α2, α3 or α5 subunits.
A study in 2005, in vitro (receptor material not specified in abstract), found valerian extract as well as valerenic acid to be 5-HT5A receptor (serotonin receptor) partial agonists. Part of the binding studies focused on the 5HT5A receptor, which is distributed in the suprachiasmatic nucleus. This is a tiny region of the brain, which is implicated in the sleep-wake cycle.
A study in 2006 found valerian extract as well as valerenic acid to inhibit NF-κB, a protein complex that controls the transcription of DNA, in HeLa (cultured human cancer) cells. This was measured with the IL-6 / Luc (Interleukin-6 luciferase) assay as a measurement tool. The study mentioned that such inhibition may be connected to the reported anti-inflammatory action of the valerian plant.
- Yuan, C. S.; Mehendale, S.; Xiao, Y.; Aung, H. H.; Xie, J. T.; Ang-Lee, M. K. (2004). "The gamma-aminobutyric acidergic effects of valerian and valerenic acid on rat brainstem neuronal activity" (pdf). Anesthesia and Analgesia 98 (2): 353–358. doi:10.1213/01.ANE.0000096189.70405.A5. PMID 14742369.
- Khom, S.; Baburin, I.; Timin, E.; Hohaus, A.; Trauner, G.; Kopp, B.; Hering, S. (2007). "Valerenic acid potentiates and inhibits GABAA receptors: Molecular mechanism and subunit specificity". Neuropharmacology 53 (1): 178–187. doi:10.1016/j.neuropharm.2007.04.018. PMID 17585957.
- Dietz, B.; Mahady, G.; Pauli, G.; Farnsworth, N. (2005). "Valerian extract and valerenic acid are partial agonists of the 5-HT receptor in vitro". Molecular Brain Research 138 (2): 191–197. doi:10.1016/j.molbrainres.2005.04.009. PMID 15921820.
- Jacobo-Herrera, N. J.; Vartiainen, N.; Bremner, P.; Gibbons, S.; Koistinaho, J.; Heinrich, M. (2006). "F-κB modulators from Valeriana officinalis". Phytotherapy Research 20 (10): 917–919. doi:10.1002/ptr.1972. PMID 16909443.
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