title: Antioxidant activity of rosmarinic acid and its principal metabolites in chemical and cellular systems: Importance of physico-chemical characteristics.
abstract: Persistent accumulation of reactive oxygen species causes cellular oxidative stress which contributes strongly towards the induction and progression of various diseases. Therapeutic focus has therefore shifted towards the use of antioxidants, with recent interest in those of plant origin. In the current study, rosmarinic acid (RA) and its key metabolites were evaluated in non-cellular and cellular antioxidant assays, using quercetin (Q) as a positive control. The non-cellular assay was performed as scavenging of DPPH radical, whilst the cellular assay was performed as protection from an oxidant stress. Radical-scavenging activity of RA and two of its primary metabolites, CA and DHPLA, were comparable to that of Q, whilst FA was of lower potency and m-CoA was inactive. In the cellular assay, RA and CA were markedly less potent than Q, with DHPLA, FA and m-CoA being inactive, this being true in short-term (5-h) or long-term (20-h) exposure conditions. However, antioxidant potency of Q and methyl rosmarinate, a non-ionisable ester of RA, was similar in the non-cellular and short-term cellular assays. It is proposed that marked ionisation of organic acids such as RA and its metabolites at physiological pH greatly limits their intracellular accumulation, and so attenuates intrinsic antioxidant ability demonstrated in the non-cellular assay. This study demonstrates some of the factors that prevent well-known phytochemicals from progressing further along the drug discovery chain.
authors.affiliation: School of Life Sciences, University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, UK. Electronic address: mbxaa12@nottingham.ac.uk.
authors.forename: Amma G
authors.initials: AG
authors.lastname: Adomako-Bonsu
authors.affiliation: School of Life Sciences, University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, UK.
authors.forename: Sue Lf
authors.initials: SL
authors.lastname: Chan
authors.affiliation: School of Life Sciences, University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, UK.
authors.forename: Margaret
authors.initials: M
authors.lastname: Pratten
authors.affiliation: School of Life Sciences, University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, UK.
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Fry
mesh_terms: D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000737:chemistry; D002109:Caffeic Acids / Q000737:chemistry / Q000494:pharmacology; D002934:Cinnamates / Q000737:chemistry / Q000494:pharmacology*; D003373:Coumaric Acids / Q000737:chemistry / Q000494:pharmacology; D053630:Depsides / Q000737:chemistry / Q000494:pharmacology*; D056945:Hep G2 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D018384:Oxidative Stress / Q000187:drug effects; D010851:Picrates / Q000737:chemistry; D011794:Quercetin / Q000737:chemistry / Q000494:pharmacology; D000097123:Rosmarinic Acid
chemical_list: D000975:Antioxidants; D001713:Biphenyl Compounds; D002109:Caffeic Acids; D002934:Cinnamates; D003373:Coumaric Acids; D053630:Depsides; D010851:Picrates; D011794:Quercetin; D000097123:Rosmarinic Acid; C043332:3-coumaric acid; C004999:ferulic acid; C004931:1,1-diphenyl-2-picrylhydrazyl; C040048:caffeic acid
keywords: Cytoprotection; HepG2 cells; Metabolites; Oxidative stress; Quercetin; Rosmarinic acid