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Lichen-derived compounds show potential for central nervous system therapeutics

Abstract : Background Natural products from lichens are widely investigated for their biological properties, yet their potential as central nervous system (CNS) therapeutic agents is less explored. Purpose The present study investigated the neuroactive properties of selected lichen compounds (atranorin, perlatolic acid, physodic acid and usnic acid), for their neurotrophic, neurogenic and acetylcholine esterase (AChE) activities. Methods Neurotrophic activity (neurite outgrowth) was determined using murine neuroblastoma Neuro2A cells. A MTT assay was performed to assess the cytotoxicity of compounds at optimum neurotrophic activity. Neuro2A cells treated with neurotrophic lichen compounds were used for RT-PCR to evaluate the induction of genes that code for the neurotrophic markers BDNF and NGF. Immunoblotting was used to assess acetyl H3 and H4 levels, the epigenetic markers associated with neurotrophic and/or neurogenic activity. The neurogenic property of the compounds was determined using murine hippocampal primary cultures. AChE inhibition activity was performed using a modified Ellman's esterase method. Results Lichen compounds atranorin, perlatolic acid, physodic acid and (+)-usnic acid showed neurotrophic activity in a preliminary cell-based screening based on Neuro2A neurite outgrowth. Except for usnic acid, no cytotoxic effects were observed for the two depsides (atranorin and perlatolic acid) and the alkyl depsidone (physodic acid). Perlatolic acid appears to be promising, as it also exhibited AChE inhibition activity and potent proneurogenic activity. The neurotrophic lichen compounds (atranorin, perlatolic acid, physodic acid) modulated the gene expression of BDNF and NGF. In addition, perlatolic acid showed increased protein levels of acetyl H3 and H4 in Neuro2A cells. Conclusion These lichen depsides and depsidones showed neuroactive properties in vitro (Neuro2A cells) and ex vivo (primary neural stem or progenitor cells), suggesting their potential to treat CNS disorders. © 2016 Elsevier GmbH
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https://hal-univ-rennes1.archives-ouvertes.fr/hal-01381131
Contributor : Laurent Jonchère <>
Submitted on : Friday, October 14, 2016 - 9:18:33 AM
Last modification on : Friday, July 10, 2020 - 4:19:03 PM

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R.G. Reddy, L. Veeraval, S. Maitra, M. Chollet-Krugler, S. Tomasi, et al.. Lichen-derived compounds show potential for central nervous system therapeutics. Phytomedicine, Elsevier, 2016, 23 (12), pp.1527--1534. ⟨10.1016/j.phymed.2016.08.010⟩. ⟨hal-01381131⟩

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