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J Bioenerg Biomembr (2010) 42:165172 DOI 10.1007/s10863-010-9275-x
Effects of Ginkgo biloba extract on heart and liver mitochondrial functions: mechanism(s) of action
Giedre Baliutyte & Rasa Baniene &
Sonata Trumbeckaite & Vilmante Borutaite &
Adolfas Toleikis
Received: 7 November 2009 /Accepted: 22 February 2010 /Published online: 19 March 2010 # Springer Science+Business Media, LLC 2010
Abstract Though extracts of Ginkgo biloba leaves (GBE) have a wide pharmacological application, little is known about GBE effects on mitochondria. In this work, effects of ethanolic GBE on the respiration of isolated rat heart and liver mitochondria were investigated. We found that GBE stimulates the pyruvate + malate-dependent State 2 respiration of heart mitochondria and decreases mitochondrial membrane potential. Uncoupling effect of GBE was found to be due to its protonophoric action and is likely to be mediated by the ATP/ADP-translocator and uncoupling proteins. The effect of GBE was less in liver than in heart mitochondria. State 3 respiration of heart mitochondria was slightly stimulated at low and depressed at higher GBE concentrations. Inhibition of State 3 respiration of heart mitochondria was not relieved by uncoupler indicating that GBE may inhibit the respiratory chain complexes or the substrate transport. However, Complex IV of the respiratory chain was not inhibited by GBE. H2O2 generation was attenuated by low concentration of GBE probably due to mild uncoupling. The data suggest that mild but not severe
uncoupling activity of GBE may be important in providing pharmacological protection of cellular functions in pathological situations.
Keywords Ginkgo biloba extract (GBE) . Mitochondria . Permeabilized fibers . Respiration . Uncoupling of oxidative phosphorylation
AbbreviationsANT Adenine nucleotide translocaseCAT CarboxyatractilosideCCCP Carbonylcyanide pchloromethoxyphenylhydrazoneROS Reactive oxygen speciesUCP Uncoupling proteinTMPD N,N,N,N-tetramethyl-p-phenylenediamine TPP+ Tetraphenylphosphonium
Introduction
Ginkgo biloba L. (Ginkgoaceae), originated from China, first introduced to Europe in the 18th century (Stromgaard and Nakanishi 2004), is now distributed all over the world. Over the past 20 years, Ginkgo biloba-derived preparations have become widely used in medical practice. A wide pharmacological application of Ginkgo biloba extracts (GBE) is determined by the main active substances: flavonoids (flavone glycosides, primarily composed of quercetin) and terpenoids (ginkolides and bilobalides). Due to their vasorelaxing, anticoagulant, antioxidative and anti-inflammatory properties, GBE have been most frequently prescribed as preparations that improve cerebral blood circulation and memory (Christen 2004; Luo 2001).