R Gajendra Reddy1, Lenin Veeraval1, Swati Maitra1, Marylène Chollet-Krugler2, Sophie Tomasi2, Françoise Lohézic-Le Dévéhat2, Joël Boustie3, Sumana Chakravarty4. 1. Chemical Biology, CSIR- Indian Institute of Chemical Technology, Tarnaka, Uppal Road, Hyderabad 500007, India. 2. 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. 3. 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. 4. Chemical Biology, CSIR- Indian Institute of Chemical Technology, Tarnaka, Uppal Road, Hyderabad 500007, India. Electronic address: sumana98@gmail.com.
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.
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 murineneuroblastoma 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.
Authors: Aleksandra Majchrzak-Celińska; Robert Kleszcz; Elżbieta Studzińska-Sroka; Agnieszka Łukaszyk; Anna Szoszkiewicz; Ewelina Stelcer; Karol Jopek; Marcin Rucinski; Judyta Cielecka-Piontek; Violetta Krajka-Kuźniak Journal: Cells Date: 2022-03-23 Impact factor: 6.600
Authors: Elżbieta Studzińska-Sroka; Aleksandra Majchrzak-Celińska; Przemysław Zalewski; Dominik Szwajgier; Ewa Baranowska-Wójcik; Barbara Kaproń; Tomasz Plech; Marcin Żarowski; Judyta Cielecka-Piontek Journal: Pharmaceuticals (Basel) Date: 2021-12-10