Effects of the Kielmeyera coriacea extract on energy metabolism in the rat liver
Introduction
Kielmeyera coriacea Mart is a tree of the Clusiaceae family, popularly known in Brazil as “pau-santo”. Crude aqueous extracts of the plant are traditionally used by the native population of Brazil in the treatment of several tropical diseases including schistosomiasis, leishmaniasis, malaria, and fungal or bacterial infections (Audi et al., 2002). The hydroethanolic extract of Kielmeyera coriacea seems also to act on the central nervous system in rats. This was deduced from a study in which anxiolytic and antidepressant effects were observed (Martins et al., 2004). A more recent work reports that the hydroethanolic extract of Kielmeyera coriacea is able to increase the resistance of the gastric mucosa against necrotizing agents, a property which manifests as an antiulcer activity (Goulart et al., 2005).
Analysis of the dichloromethane and hydroalcoholic extracts of Kielmeyera coriacea leaves and stems revealed the presence of several xanthones (Bennet and Lee, 1989, Cortez et al., 1998). Phytochemical investigation of these extracts resulted in the isolation and identification of 10 xanthones, two triterpenes and one biphenylic compound. Four xanthones and the biphenylic compound exhibited antifungal activity against the plant pathogenic fungus Cladosporium cucumerinum, while two prenylated xanthones inhibited the growth of Candida albicans (Cortez et al., 1998). Antimicrobial activities against Bacillus subtilis and Staphylococcus aureus by one xanthone and the biphenylic compound aucuparin, respectively, have also been reported (Cortez et al., 2002).
As mentioned above preparations of the crude plant are used for treating several infectious diseases (Audi et al., 2002), but biochemical and physiological studies are lacking. There are several reports, however, about biochemical effects of xanthone derivatives, which as mentioned above, are abundant in extracts of Kielmeyera coriacea leaves and stems (Cortez et al., 1998). Xanthones seem to be particularly active on mitochondrial functions (Kawai et al., 1983, Kawai et al., 1984). On the other hand, an action on the mitochondrial functions could bear some relation to the popular use of Kielmeyera coriacea against protozoan, fungal and bacterial infections. For example, there are well documented examples of drugs used in protozoal infections (hydroxynaphthoquinones) whose mechanism of action includes inhibition of mitochondrial functions (Hudson et al., 1985, Tracy and Webster, 1996). An action of Kielmeyera coriacea extracts on energy metabolism is thus a real possibility which is explored in the present work by experiments with isolated mitochondria and with the perfused rat liver. In isolated rat liver mitochondria the respiratory activity, oxidative phosphorylation and several membrane-bound enzymatic activities were measured. In order to see how possible effects of the Kielmeyera coriacea extracts manifest in intact cells, several parameters related to energy metabolism were measured in the perfused rat liver. These parameters include, oxygen uptake, glycogenolysis, glycolysis and gluconeogenesis.
Section snippets
Plant material
Kielmeyera coriacea was collected near Mogi-Guaçu (São Paulo, Brazil) in April, 2003 and identified by Dr. Young, of the Botany Institute of São Paulo (Avenida Miguel Stefano, 3687, P.O. Box 4005, São Paulo, Brazil). A voucher specimen (number SP 298-463) has been deposited in the Botany Institute of São Paulo. The standardized extract of Kielmeyera coriacea stems was registered by the University of Maringá under patent application #001342 in the Brazilian National Patents Institute (INPI) on 9
Effects of the extract of Kielmeyera coriacea on oxygen consumption in isolated mitochondria
Oxygen consumption by intact mitochondria was measured using NAD+-dependent (α-ketoglutarate) and FAD-dependent (succinate) substrates in the presence of exogenously added ADP (state III respiration) or after ADP exhaustion (state IV respiration). The extract of the Kielmeyera coriacea stem was added to the incubation medium for final concentrations between 0.6 and 10 μg/ml when α-ketoglutarate was the substrate, while concentrations in the range of 0.6–20 μg/ml were tested with succinate. The
Discussion
The results of the present work show that the extract of Kielmeyera coriacea exerts multiple effects on liver metabolism. The rat liver perfusion experiments provide evidence that the Kielmeyera coriacea extract influences glucose and glycogen metabolism. It activates oxygen consumption either in livers from fed or fasted rats. It is unlikely that this activation could be a consequence of increases in the energy requirement of the liver, because a significant reduction in gluconeogenesis
Acknowledgements
This work was supported by grants from the Programa Nacional de Núcleos de Excelência (PRONEX), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq).
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