Pharmacopsychiatry 2021; 54(01): 37-46
DOI: 10.1055/a-1293-8585
Original Paper

Neurotrophic Properties of Silexan, an Essential Oil from the Flowers of Lavender-Preclinical Evidence for Antidepressant-Like Properties

Kristina Friedland
1   Pharmacology and Toxicology, Institute for Pharmacy and Biomedical Sciences, Johannes Gutenberg-University Mainz, Germany
,
Giacomo Silani
2   Department of Pharmacology, Biocenter, Goethe-University Frankfurt, Germany
,
Anita Schuwald
2   Department of Pharmacology, Biocenter, Goethe-University Frankfurt, Germany
,
Carola Stockburger
2   Department of Pharmacology, Biocenter, Goethe-University Frankfurt, Germany
,
Egon Koch
3   Preclinical Research, Dr. Willmar Schwabe Pharmaceuticals, Karlsruhe, Germany
,
Michael Nöldner
3   Preclinical Research, Dr. Willmar Schwabe Pharmaceuticals, Karlsruhe, Germany
,
Walter E. Müller
2   Department of Pharmacology, Biocenter, Goethe-University Frankfurt, Germany
› Author Affiliations
Funding The experiments were supported by a resaearch grant from Dr. Willmar Schwabe Pharmaceuticals (Karlsruhe, Germany).

Abstract

Background Silexan, a special essential oil from flowering tops of lavandula angustifolia, is used to treat subsyndromal anxiety disorders. In a recent clinical trial, Silexan also showed antidepressant effects in patients suffering from mixed anxiety-depression (ICD-10 F41.2). Since preclinical data explaining antidepressant properties of Silexan are missing, we decided to investigate if Silexan also shows antidepressant-like effects in vitro as well as in vivo models.

Methods We used the forced swimming test (FST) in rats as a simple behavioral test indicative of antidepressant activity in vivo. As environmental events and other risk factors contribute to depression through converging molecular and cellular mechanisms that disrupt neuronal function and morphology—resulting in dysfunction of the circuitry that is essential for mood regulation and cognitive function—we investigated the neurotrophic properties of Silexan in neuronal cell lines and primary hippocampal neurons.

Results The antidepressant activity of Silexan (30 mg/kg BW) in the FST was comparable to the tricyclic antidepressant imipramine (20 mg/kg BW) after 9-day treatment. Silexan triggered neurite outgrowth and synaptogenesis in 2 different neuronal cell models and led to a significant increase in synaptogenesis in primary hippocampal neurons. Silexan led to a significant phosphorylation of protein kinase A and subsequent CREB phosphorylation.

Conclusion Taken together, Silexan demonstrates antidepressant-like effects in cellular as well as animal models for antidepressant activity. Therefore, our data provides preclinical evidence for the clinical antidepressant effects of Silexan in patients with mixed depression and anxiety.



Publication History

Received: 04 May 2020
Received: 27 September 2020

Accepted: 30 September 2020

Article published online:
30 November 2020

© 2020. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

  • 1 Kumar V. Characterization of anxiolytic and neuropharmacological activities of Silexan. Wiener Medizinische Wochenschrift 2013; 163: 89-94
  • 2 Schuwald AM, Nöldner M, Wilmes T. et al. Lavender oil-potent anxiolytic properties via modulating voltage dependent calcium channels. PLoS One 2013; 8: e59998
  • 3 Müller WE, Schuwald A, Nöldner N. et al. Pharmacological basis of the therapeutical use of Silexan (Lasea). Psychopharmakotherapie 2015; 22: 3-14
  • 4 Kasper S, Müller WE, Volz H-P. et al. Silexan in anxiety disorders: Clinical data and pharmacological background. World J Biol Psychiatry 2018; 19: 412-420
  • 5 Kasper S, Gastpar M, Müller WE. et al. Efficacy and safety of silexan, a new, orally administered lavender oil preparation, in subthreshold anxiety disorder - evidence from clinical trials. Wien Med Wochenschr 2010; 160: 547-556
  • 6 Kasper S. An orally administered lavandula oil preparation (Silexan) for anxiety disorder and related conditions: An evidence based review. Int J Psychiatry Clin Pract 2013; 17: 15-22
  • 7 Kasper S. Phytopharmaceutical treatment of anxiety, depression, and dementia in the elderly: evidence from randomized, controlled clinical trials. Wien Med Wochenschr 2015; 165: 217-228
  • 8 Kasper S, Gastpar M, Müller WE. et al. Lavender oil preparation Silexan is effective in generalized anxiety disorder - a randomized, double-blind comparison to placebo and paroxetine. Int J Neuropsychopharmacol 2014; 1-11
  • 9 López V, Nielsen B, Solas M. et al. K. Exploring pharmacological mechanisms of lavender (Lavandula angustifolia) essential oil on central nervous system targets. Front Pharmacol 2017; 8: 280
  • 10 El Alaoui C, Chemin J, Fechtali T. et al. Modulation of T-type Ca2+ channels by Lavender and Rosemary extracts. PLoS One 2017; 12: e0186864
  • 11 Kavoussi R. Pregabalin: From molecule to medicine. Eur Neuropsychopharmacol 2006; 16 Suppl 2 S128-S133
  • 12 Kaur S, Maslov LN, Singh N. et al. Dual role of T-type calcium channels in anxiety-related behavior. J Basic Clin Physiol Pharmacol 2019;
  • 13 Kasper S, Dienel A. Silexan (WS® 1265) vermindert begleitende depressive Symptome bei Patienten mit Angsterkrankungen. Zeitschrift für Phyther 2013; 34: V01
  • 14 Kasper S, Volz H-P, Dienel A. et al. Efficacy of Silexan in mixed anxiety-depression – A randomized, placebo-controlled trial. Eur Neuropsychopharmacol 2016; 26: 331-340
  • 15 Pavlovicova M, Lacinova L, Dremencov E. Review Cellular and molecular mechanisms underlying the treatment of depression: Focusing on hippocampal G-protein-coupled receptors and voltage-dependent calcium channels. Gen Physiol Biophys 2015; 34: 353-366
  • 16 Nanou E, Catterall WA. Calcium channels, synaptic plasticity, and neuropsychiatric disease. Neuron 2018; 98: 466-481
  • 17 Normann C, Frase S, Haug V. et al. Antidepressants rescue stress-induced disruption of synaptic plasticity via serotonin transporter–independent inhibition of l-type calcium channels. Biol Psychiatry 2018; 84: 55-64
  • 18 Leuner K, Kazanski V, Müller M. et al. Hyperforin – a key constituent of St. John’s wort specifically activates TRPC6 channels. FASEB J 2007; 21: 4101-4111
  • 19 Heiser JH, Schuwald AM, Sillani G. et al. TRPC6 channel-mediated neurite outgrowth in PC12 cells and hippocampal neurons involves activation of RAS/MEK/ERK, PI3K, and CAMKIV signaling. J Neurochem 2013; 127: 303-313
  • 20 Stockburger C, Gold VAM, Pallas T. et al. A cell model for the initial phase of sporadic Alzheimer’s disease. J Alzheimers Dis 2014; 42: 395-411
  • 21 Leuner K, Li W, Amaral MD. et al. Hyperforin modulates dendritic spine morphology in hippocampal pyramidal neurons by activating Ca(2+) -permeable TRPC6 channels. Hippocampus 2013; 23: 40-52
  • 22 Porsolt RD, Le Pichon M, Jalfre M. Depression: A new animal model sensitive to antidepressant treatments [27]. Nature 1977; 266: 730-732
  • 23 Gururajan A, Reif A, Cryan JF. et al. The future of rodent models in depression research. Nat Rev Neurosci 2019; 20: 686-701
  • 24 Boczek T, Ferenc B, Lisek M. et al. Regulation of GAP43/calmodulin complex formation via calcineurin-dependent mechanism in differentiated PC12 cells with altered PMCA isoforms composition. Mol Cell Biochem 2015; 407: 251-262
  • 25 Duman RS, Aghajanian GK, Sanacora G. et al. Synaptic plasticity and depression: new insights from stress and rapid-acting antidepressants. Nat Med 2016; 22: 238-249
  • 26 Gerdin MJ, Eiden LE. Regulation of PC12 cell differentiation by cAMP signaling to ERK independent of PKA: do all the connections add up?. Sci STKE 2007; 2007: 11-15
  • 27 Vaudry D, Stork PJS, Lazarovici P. et al. Signaling pathways for PC12 cell differentiation: Making the right connections. Science (80- ) 2002; 296: 1648-1649
  • 28 Sheng B, Wang X, Su B. et al. Impaired mitochondrial biogenesis contributes to mitochondrial dysfunction in Alzheimer’s disease. J Neurochem 2012; 120: 419-429
  • 29 Sánchez-Vidaña DI, Po KKT, Fung TKH. et al. Lavender essential oil ameliorates depression-like behavior and increases neurogenesis and dendritic complexity in rats. Neurosci Lett 2019; 701: 180-192
  • 30 Sanna MD, Les F, Lopez V. et al. Lavender (Lavandula angustifolia Mill.) essential oil alleviates neuropathic pain in mice with spared nerve injury. Front Pharmacol 2019; 10: 472
  • 31 Duman RS, Aghajanian GK. Synaptic dysfunction in depression: Potential therapeutic targets. Science 2012; 338: 68-72
  • 32 Harmer CJ, Duman RS, Cowen PJ. How do antidepressants work? New perspectives for refining future treatment approaches. The lancet Psychiatry 2017; 4: 409-418
  • 33 Yamamoto XK, Kobayashi XM. Opposite Roles in Short-Term Plasticity for N-Type and P / Q-Type Voltage-Dependent Calcium Channels in GABAergic Neuronal Connections in the Rat Cerebral Cortex 2018; 38: 9814-9828
  • 34 Catterall WA, Leal K, Nanou E. Calcium channels and short-term synaptic plasticity. J Biol Chem 2013; 288: 10742-10749
  • 35 Grewal SS, York RD, Stork PJ. Extracellular-signal-regulated kinase signalling in neurons. Curr Opin Neurobiol 1999; 9: 544-553