title: 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.
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Chemical Biology, CSIR- Indian Institute of Chemical Technology, Tarnaka, Uppal Road, Hyderabad 500007, India.
authors.forename: R Gajendra
authors.initials: RG
authors.lastname: Reddy
authors.affiliation: Chemical Biology, CSIR- Indian Institute of Chemical Technology, Tarnaka, Uppal Road, Hyderabad 500007, India.
authors.forename: Lenin
authors.initials: L
authors.lastname: Veeraval
authors.affiliation: Chemical Biology, CSIR- Indian Institute of Chemical Technology, Tarnaka, Uppal Road, Hyderabad 500007, India.
authors.forename: Swati
authors.initials: S
authors.lastname: Maitra
authors.affiliation: PNSCM-UMRCNRS 6226, ISCR, Faculté des Sciences Pharmaceutiques et Biologiques, Université Européenne de Bretagne, Université de Rennes 1, 2 Av. du Pr Léon Bernard, 35043 Rennes Cedex, France.
authors.forename: Marylène
authors.initials: M
authors.lastname: Chollet-Krugler
authors.affiliation: PNSCM-UMRCNRS 6226, ISCR, Faculté des Sciences Pharmaceutiques et Biologiques, Université Européenne de Bretagne, Université de Rennes 1, 2 Av. du Pr Léon Bernard, 35043 Rennes Cedex, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Tomasi
authors.affiliation: PNSCM-UMRCNRS 6226, ISCR, Faculté des Sciences Pharmaceutiques et Biologiques, Université Européenne de Bretagne, Université de Rennes 1, 2 Av. du Pr Léon Bernard, 35043 Rennes Cedex, France.
authors.forename: Françoise Lohézic-Le
authors.initials: FL
authors.lastname: Dévéhat
authors.affiliation: PNSCM-UMRCNRS 6226, ISCR, Faculté des Sciences Pharmaceutiques et Biologiques, Université Européenne de Bretagne, Université de Rennes 1, 2 Av. du Pr Léon Bernard, 35043 Rennes Cedex, France. Electronic address: joel.boustie@univ-rennes1.fr.
authors.forename: Joël
authors.initials: J
authors.lastname: Boustie
authors.affiliation: Chemical Biology, CSIR- Indian Institute of Chemical Technology, Tarnaka, Uppal Road, Hyderabad 500007, India. Electronic address: sumana98@gmail.com.
authors.forename: Sumana
authors.initials: S
authors.lastname: Chakravarty
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001565:Benzoates / Q000494:pharmacology* / Q000627:therapeutic use; D001572:Benzofurans / Q000494:pharmacology* / Q000627:therapeutic use; D001688:Biological Products / Q000494:pharmacology / Q000627:therapeutic use; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002490:Central Nervous System / Q000187:drug effects* / Q000378:metabolism; D002493:Central Nervous System Diseases / Q000188:drug therapy / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D053630:Depsides / Q000494:pharmacology* / Q000627:therapeutic use; D003990:Dibenzoxepins / Q000494:pharmacology* / Q000627:therapeutic use; D015870:Gene Expression; D062385:Hydroxybenzoates / Q000494:pharmacology* / Q000627:therapeutic use; D007783:Lactones / Q000494:pharmacology* / Q000627:therapeutic use; D008011:Lichens / Q000737:chemistry*; D051379:Mice; D020932:Nerve Growth Factor / Q000235:genetics / Q000378:metabolism; D058953:Neural Stem Cells; D055495:Neurogenesis / Q000187:drug effects / Q000235:genetics
chemical_list: D001565:Benzoates; D001572:Benzofurans; D001688:Biological Products; D019208:Brain-Derived Neurotrophic Factor; D002800:Cholinesterase Inhibitors; D053630:Depsides; D003990:Dibenzoxepins; D062385:Hydroxybenzoates; D007783:Lactones; C522034:perlatolic acid; C073339:usnic acid; C000875:depsidone; C026304:atranorin; D020932:Nerve Growth Factor; D000110:Acetylcholinesterase; C043056:physodic acid
keywords: Lichen; Neuro2A; Neurogenic activity; Neurosphere assay; Neurotrophic activity; Perlatolic acid