title: Evaluation of the cytotoxic and mutagenic potential of three ginkgolic acids.
abstract: Ginkgolic acids (GAs) are alkylphenols which can be found in the fruits and leaves of Ginkgo biloba L. (Ginkgoaceae) used in herbal teas, drugs and food supplements. Standardized leaf extracts of G. biloba are widely used in the therapy of cognitive decline including Alzheimer's diseases. However, GAs are known to have cytotoxic and allergenic potential and are suspected to possess genotoxic properties. Therefore, we examined in this study the cytotoxicity and mutagenicity of three major GAs with different alkyl or alkenyl groups (13:0, 15:1, 17:1). Cytotoxicity was assessed in male Chinese hamster lung fibroblasts (V79 cells) using the resazurin reduction assay. The substances showed concentration dependent cytotoxic effects after 24h of incubation at concentrations of 50μM and higher. Mutagenicity was determined by using the Ames fluctuation assay in different Salmonella typhimurium strains (TA97a, TA98, TA100 and TA102) with and without exogenous metabolic activation (S9 mix). Furthermore, we analyzed the mutagenic potency of the three major GAs in V79 cells by performing the hypoxanthine phosphoribosyl transferase (HPRT) assay which detects gene mutations at the HPRT locus. None of the mutagenic assays showed any increase in mutagenicity above background. Therefore, these data provide evidence that the GAs tested have some cytotoxic potency but are not mutagenic. Thus, our findings contribute to the risk assessment of preparations containing plant extracts from G. biloba.
authors.affiliation: Food Chemistry and Toxicology, University of Kaiserslautern, Erwin-Schrödinger-Str. 52, 67663 Kaiserslautern, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Berg
authors.affiliation: Food Chemistry and Toxicology, University of Kaiserslautern, Erwin-Schrödinger-Str. 52, 67663 Kaiserslautern, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Braun
authors.affiliation: Food Chemistry and Toxicology, University of Kaiserslautern, Erwin-Schrödinger-Str. 52, 67663 Kaiserslautern, Germany.
authors.forename: Isabel
authors.initials: I
authors.lastname: Krug
authors.affiliation: Food Chemistry and Toxicology, University of Kaiserslautern, Erwin-Schrödinger-Str. 52, 67663 Kaiserslautern, Germany. Electronic address: schrenk@rhrk.uni-kl.de.
authors.forename: Dieter
authors.initials: D
authors.lastname: Schrenk
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D006224:Cricetinae; D003412:Cricetulus; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D008297:Male; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D012459:Salicylates / Q000737:chemistry / Q000633:toxicity*; D018675:Toxicity Tests
chemical_list: D009153:Mutagens; D012459:Salicylates; C112485:ginkgolic acid; D007041:Hypoxanthine Phosphoribosyltransferase
keywords: Ames’ test; Cytotoxicity; Ginkgobiloba; Ginkgolic acids; HPRT assay; Mutagenicity