RESUMO
Arctigenin is a bioactive dibenzylbutyrolactone-type lignan exhibiting various pharmacological activities. The neuroprotective effects of arctigenin were demonstrated to be mediated via inhibition of AMPA and KA type glutamate receptors in the somatosensory cortex of the rat brain. The aim of this study was to compare the effects of arctigenin with matairesinol and trachelogenin on synaptic activity in ex vivo rat brain slices. Arctigenin, matairesinol and trachelogenin were isolated from Arctium lappa, Centaurea scabiosa and Cirsium arvense, respectively, and applied on brain slices via perfusion medium at the concentration range of 0.5â-â40 µM. The effects of the lignans were examined in the CA1 hippocampus and the somatosensory cortex by recording electrically evoked field potentials. Arctigenin and trachelogenin caused a significant dose-dependent decrease in the amplitude of hippocampal population spikes (POPS) and the slope of excitatory postsynaptic potentials (EPSPs), whereas matairesinol (1 µM and 10 µM) decreased EPSP slope but had no effect on POPS amplitude. Trachelogenin effect (0.5 µM, 10 µM, 20 µM) was comparable to arctigenin (1 µM, 20 µM, 40 µM) (p > 0.05). In the neocortex, arctigenin (10 µM, 20 µM) and trachelogenin (10 µM) significantly decreased the amplitude of evoked potential early component, while matairesinol (1 µM and 10 µM) had no significant effect (p > 0.05). The results suggest that trachelogenin and arctigenin act via inhibition of AMPA and KA receptors in the brain and trachelogenin has a higher potency than arctigenin. Thus, trachelogenin and arctigenin could serve as lead compounds in the development of neuroprotective drugs.
Assuntos
Lignanas , Ratos , Animais , Ácido alfa-Amino-3-hidroxi-5-metil-4-isoxazol Propiônico , Lignanas/farmacologia , HipocampoRESUMO
The directed causal relationship were examined between the local field potential (LFP) and the intrinsic optical signal (IOS) during induced epileptiform activity in in vitro cortical slices by the convergent cross-mapping causality analysis method. Two components of the IOS signal have been distinguished: a faster, activity dependent component (IOSh) which changes its sign between transmitted and reflected measurement, thus it is related to the reflectance or the scattering of the tissue and a slower component (IOSl), which is negative in both cases, thus it is resulted by the increase of the absorption of the tissue. We have found a strong, unidirectional, delayed causal effect from LFP to IOSh with 0.5-1s delay, without signs of feedback from the IOSh to the LFP, while the correlation was small and the peaks of the cross correlation function did not reflect the actual causal dependency. Based on these observations, a model has been set up to describe the dependency of the IOSh on the LFP power and IOSh was reconstructed, based on the LFP signal. This study demonstrates that causality analysis can lead to better understanding the physiological interactions, even in case of two data series with drastically different time scales.
Assuntos
Potenciais de Ação/fisiologia , Epilepsia/fisiopatologia , Fenômenos Ópticos , Processamento de Sinais Assistido por Computador , Animais , Simulação por Computador , Masculino , Ratos Wistar , Fatores de TempoRESUMO
Lignans are biologically active phenolic compounds related to lignin, produced in different plants. Arctigenin, a dibenzylbutyrolactone-type lignan, has been used as a neuroprotective agent for the treatment of encephalitis. Previous studies of cultured rat cerebral cortical neurones raised the possibility that arctigenin inhibits kainate-induced excitotoxicity. The aims of the present study were: 1) to analyse the effect of arctigenin on normal synaptic activity in ex vivo brain slices, 2) to determine its receptor binding properties and test the effect of arctigenin on AMPA/kainate receptor activation and 3) to establish its effects on neuronal activity in vivo. Arctigenin inhibited glutamatergic transmission and reduced the evoked field responses. The inhibitory effect of arctigenin on the evoked field responses proved to be substantially dose dependent. Our results indicate that arctigenin exerts its effects under physiological conditions and not only on hyper-excited neurons. Furthermore, arctigenin can cross the blood-brain barrier and in the brain it interacts with kainate sensitive ionotropic glutamate receptors. These results indicate that arctigenin is a potentially useful new pharmacological tool for the inhibition of glutamate-evoked responses in the central nervous system in vivo.