title: Taxodione and Extracts from Salvia austriaca Roots as Human Cholinesterase Inhibitors.
abstract: Taxodione, an abietane diterpenoid, was isolated from Salvia austriaca transformed roots grown in in vitro conditions. The compound is known to have antibacterial, cytotoxic and anti-tumour properties. This study evaluates the ability of pure taxodione and extracts obtained from the S. austriaca hairy roots and roots from field-grown plants to inhibit human acetylcholinesterase and butyrylcholinesterase. Both extracts were found to have similar actions against acetylcholinesterase. The IC50 for extracts from transformed and untransformed roots were 142.5 and 139.5 µg ml(-1), respectively. The highest activity towards human acetylcholinesterase was demonstrated by taxodione (IC50  = 54.84 µg ml(-1)). With respect to BChE inhibition, the root extracts demonstrated stronger activity (IC50  = 23.6 µg ml(-1): field-grown plants and 41.6 µg ml(-1): transformed roots) than taxodione (IC50  = 195.9 µg ml(-1)). Taxodione showed significant cytotoxicity against A549 cell line (IC50  = 9.1 µg ml(-1)), whereas the activities for the extracts from S. austriaca roots of field-grown plants (IC50  = 75.7 µg ml(-1)) and hairy roots (IC50  = 86.2 µg ml(-1)) were lower. Computer modelling suggests that taxodione should not demonstrate cardiotoxic or genotoxic activity. It also indicates that taxodione should demonstrate very rapid transport from the body with very good blood-brain barrier penetration, but with no cumulative effect on the human body. The obtained results indicate that taxodione is a safe compound and may be used for further investigations in pharmacological activities.
authors.affiliation: Department of Biology and Pharmaceutical Botany, Medical University, Muszyńskiego 1, 90-151, Łódź, Poland.
authors.forename: Łukasz
authors.initials: Ł
authors.lastname: Kuźma
authors.affiliation: Department of Biology and Pharmaceutical Botany, Medical University, Muszyńskiego 1, 90-151, Łódź, Poland.
authors.forename: Halina
authors.initials: H
authors.lastname: Wysokińska
authors.affiliation: Department of Pharmaceutical Chemistry, Drug Analyses and Radiopharmacy, Medical University, Muszyńskiego 1, 90-151, Łódź, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Sikora
authors.affiliation: Department of Pharmaceutical Chemistry, Drug Analyses and Radiopharmacy, Medical University, Muszyńskiego 1, 90-151, Łódź, Poland.
authors.forename: Paulina
authors.initials: P
authors.lastname: Olszewska
authors.affiliation: Department of Pharmaceutical Chemistry, Drug Analyses and Radiopharmacy, Medical University, Muszyńskiego 1, 90-151, Łódź, Poland.
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Mikiciuk-Olasik
authors.affiliation: Laboratory of Radiopharmacy, Department of Pharmaceutical Chemistry, Drug Analyses and Radiopharmacy, Medical University, Muszyńskiego 1, 90-151, Łódź, Poland.
authors.forename: Paweł
authors.initials: P
authors.lastname: Szymański
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000187:drug effects; D002091:Butyrylcholinesterase / Q000378:metabolism; D002460:Cell Line; D002800:Cholinesterase Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D004224:Diterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D008956:Models, Chemical; D010936:Plant Extracts / Q000494:pharmacology*; D018517:Plant Roots / Q000737:chemistry; D027544:Salvia / Q000737:chemistry*
chemical_list: D002800:Cholinesterase Inhibitors; D004224:Diterpenes; D010936:Plant Extracts; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase; C009387:taxodione
keywords: Ellman method; cholinesterase inhibitors; diterpenoids; transformed roots