title: Chemo-protective and regenerative effects of diarylheptanoids from the bark of black alder (Alnus glutinosa) in human normal keratinocytes.
abstract: Medicinal plants are recognized from ancient times as a source of diverse therapeutic agents and many of them are used as dietary supplements. Comprehensive approaches are needed that would identify bioactive components with evident activity against specific indications and provide a better link between science (ethno-botany, chemistry, biology and pharmacology) and market. Recently, the bark of black alder (Alnus glutinosa) appeared at market in the form of food supplement for treatment of different skin conditions. This study aimed to evaluate protective effects of two diarylheptanoids isolated from the bark of black alder: platyphylloside, 5(S)-1,7-di(4-hydroxyphenyl)-3-heptanone-5-O-β-D-glucopyranoside (1) and its newly discovered analog 5(S)-1,7-di(4-hydroxyphenyl)-5-O-β-D-[6-(E-p-coumaroylglucopyranosyl)]heptane-3-one (2) towards doxorubicin damaging activity. To that end, we employed HaCaT cells, non-cancerous human keratinocytes commonly used for skin regenerative studies. Diarylheptanoids significantly antagonized the effects of doxorubicin by lowering the sensitivity of HaCaT cells to this drug. Compound 2 prevented doxorubicin-induced cell death by activating autophagy. Both 1 and 2 protected HaCaT cells against doxorubicin-induced DNA damage. They significantly promoted migration and affected F-actin distribution. These results indicate that chemo-protective effects of diarylheptanoids may occur at multiple subcellular levels. Therefore, diarylheptanoids 1 and 2 could be considered as protective agents for non-cancerous dividing cells during chemotherapy.
authors.affiliation: Institute for Biological Research, Department of Neurobiology, University of Belgrade, Bulevar Despota Stefana 142, Belgrade, Serbia. Electronic address: jelena.dinic@ibiss.bg.ac.rs.
authors.forename: Jelena
authors.initials: J
authors.lastname: Dinić
authors.affiliation: Institute for Biological Research, Department of Neurobiology, University of Belgrade, Bulevar Despota Stefana 142, Belgrade, Serbia.
authors.forename: Teodora
authors.initials: T
authors.lastname: Ranđelović
authors.affiliation: Institute for Biological Research, Department of Neurobiology, University of Belgrade, Bulevar Despota Stefana 142, Belgrade, Serbia.
authors.forename: Tijana
authors.initials: T
authors.lastname: Stanković
authors.affiliation: Institute for Biological Research, Department of Neurobiology, University of Belgrade, Bulevar Despota Stefana 142, Belgrade, Serbia.
authors.forename: Miodrag
authors.initials: M
authors.lastname: Dragoj
authors.affiliation: Faculty of Medicine, University of Belgrade, Doktora Subotića 8, Belgrade, Serbia.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Isaković
authors.affiliation: Institute for Chemistry, Technology and Metallurgy, University of Belgrade, Studentski trg 12-16, Belgrade, Serbia.
authors.forename: Miroslav
authors.initials: M
authors.lastname: Novaković
authors.affiliation: Institute for Biological Research, Department of Neurobiology, University of Belgrade, Bulevar Despota Stefana 142, Belgrade, Serbia. Electronic address: camala@ibiss.bg.ac.rs.
authors.forename: Milica
authors.initials: M
authors.lastname: Pešić
mesh_terms: D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D018736:DNA Adducts; D004249:DNA Damage / Q000187:drug effects; D036381:Diarylheptanoids / Q000737:chemistry* / Q000302:isolation & purification; D004317:Doxorubicin; D005960:Glucosides / Q000737:chemistry / Q000302:isolation & purification; D006801:Humans; D030017:Ilex / Q000737:chemistry*; D015603:Keratinocytes / Q000187:drug effects*; D015394:Molecular Structure; D024301:Plant Bark / Q000737:chemistry*; D020011:Protective Agents / Q000737:chemistry / Q000302:isolation & purification
chemical_list: C000603097:5-1,7-di(4-hydroxyphenyl)-5-O-(6-(p-coumaroylglucopyranosyl))heptane-3-one; D018736:DNA Adducts; D036381:Diarylheptanoids; D005960:Glucosides; D020011:Protective Agents; C031902:doxorubicin-DNA; C000603096:platyphylloside 1,7-di(4-hydroxyphenyl)-3-heptanone-5-O-glucopyranoside; D004317:Doxorubicin
keywords: Cell motility; Chemoprotection; Curcumin; DNA damage; Diarylheptanoid; Doxorubicin