A Strong Protective Action of Guttiferone-A, a Naturally Occurring Prenylated Benzophenone, Against Iron-Induced Neuronal Cell Damage

• Published in: Journal of Pharmacological Sciences Vol. 116; no. 1; pp. 36 - 46
• Main Authors: Figueredo, Yanier Núñez, García-Pupo, Laura, Rubio, Osmany Cuesta, Hernández, René Delgado, Naal, Zeki, Curti, Carlos, Pardo Andreu, Gilberto L.
• Format: Journal Article
• Language: English
• Published: Japan Elsevier B.V 2011; The Japanese Pharmacological Society; Elsevier
• Subjects: Animals; antioxidant; Antioxidants - chemistry; Antioxidants - pharmacology; Ascorbic Acid - chemistry; Ascorbic Acid - toxicity; Benzophenones - chemistry; Benzophenones - pharmacology; Cell Survival - drug effects; Cells, Cultured; Cerebral Cortex - cytology; Cerebral Cortex - drug effects; Deoxyribose - metabolism; Embryo, Mammalian; Ferric Compounds - chemistry; Ferric Compounds - toxicity; guttiferone-A; iron; Iron Chelating Agents - chemistry; Iron Chelating Agents - pharmacology; iron chelation; Kinetics; Malondialdehyde - metabolism; Neurons - drug effects; Neurons - metabolism; neuroprotection; Neuroprotective Agents - chemistry; Neuroprotective Agents - pharmacology; Oxidants - chemistry; Oxidants - toxicity; Oxidation-Reduction - drug effects; Oxidative Stress - drug effects; PC12 Cells; Rats; Rats, Wistar; iron chelation; iron; antioxidant; guttiferone-A; neuroprotection
• ISSN: 1347-8613; 1347-8648
• DOI: 10.1254/jphs.10273FP

Guttiferone-A (GA) is a natural occurring polyisoprenylated benzophenone with several reported pharmacological actions. We have assessed the protective action of GA on iron-induced neuronal cell damage by employing the PC12 cell line and primary culture of rat cortical neurons (PCRCN). A strong protection by GA, assessed by the 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carbox-anilide (XTT) assay, was revealed, with IC50 values <1 μM. GA also inhibited Fe3+–ascorbate reduction, iron-induced oxidative degradation of 2-deoxiribose, and iron-induced lipid peroxidation in rat brain homogenate, as well as stimulated oxygen consumption by Fe2+ autoxidation. Absorption spectra and cyclic voltammograms of GA–Fe2+/ Fe3+ complexes suggest the formation of a transient charge transfer complex between Fe2+ and GA, accelerating Fe2+ oxidation. The more stable Fe3+ complex with GA would be unable to participate in Fenton-Haber Weiss-type reactions and the propagation phase of lipid peroxidation. The results show a potential of GA against neuronal diseases associated with iron-induced oxidative stress.