RESUMEN
OBJECTIVE: Traditional Mongolian Medicine (TMM) exhibits useful biological activities including antifungal, antibacterial, and anti-inflammatory actions. The mechanisms of TMM in anti-inflammation were still unclear. The aim of this study was to investigate the effects of the three main monomers (geniposide, gallate, berberine hydrochloride and a mixture of them) of a traditional Mongolian medicine on cell survival and the proinflammatory cytokines signaling pathways which are activated by bacterial lipopolysaccharides (LPS). MATERIALS AND METHODS: Mouse macrophage-like cell line RAW264.7 was used as a model of inflammation to investigate the anti-inflammatory effects of three TMM momomers and their combination. RT-PCR and Western blot was used to quantify the change of mRNA and protein levels of cytokines, Toll-like receptor-4 (TLR4) and Nuclear Factor-κB (NF-κB) and its inhibitor IκB. The non-radioactive electrophoresis mobility shift assay (EMSA) was used to evaluate the binding activity of NF-κB. RESULTS: The monomers and their combination exhibited a potent anti-inflammatory effect for suppressing the LPS-evoked secretion of proinflammatory cytokines IL-1ß, IL-6 and TNFα. Furthermore, the monomers and their combination attenuated activation of NF-κB and expression of TLR4 at both mRNA and protein levels, the upstream player of the LPS-TLR4-cytokines/ NF-κB signaling pathway. CONCLUSIONS: The Mongolia herbal compound exerts a potent anti-inflammatory effect and could potentially be developed as a useful agent for the chemo-prevention of inflammatory diseases.
Asunto(s)
Antiinflamatorios/farmacología , Berberina/farmacología , Ácido Gálico/farmacología , Iridoides/farmacología , Macrófagos/efectos de los fármacos , Medicina Tradicional Mongoliana , Animales , Línea Celular , Supervivencia Celular/efectos de los fármacos , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Lipopolisacáridos/farmacología , Macrófagos/metabolismo , Ratones , FN-kappa B/metabolismo , Receptor Toll-Like 4/genética , Receptor Toll-Like 4/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
The anterior cingulate cortex (ACC) has been demonstrated to play an important role in the affective dimension of pain. Although much evidence has pointed to an increased excitatory synaptic transmission in the ACC in some of the pathological pain state, the inhibitory synaptic transmission in this process has not been well studied. Also, the overall changes of excitatory and inhibitory synaptic transmission have not been comparatively studied in an animal model displaying both long-term persistent nociception and hyperalgesia. Here we used patch clamp recordings in ACC brain slices to observe the changes in synaptic transmission in a pain model induced by peripheral bee venom injection. First, we show that, comparing with those of naive and saline controlled rats, there was a significant increase in spike frequency in ACC neurons harvested from rats after 2 h period of peripheral persistent painful stimuli. Second, it is further shown that the frequency, amplitude and half-width were all increased in spontaneous excitatory post-synaptic currents (sEPSCs), while the amplitude of spontaneous inhibitory post-synaptic currents (sIPSCs) was decreased. The recordings of miniature post-synaptic currents demonstrate an increase in frequency of miniature excitatory post-synaptic currents (mEPSCs) and a decrease in both frequency and amplitude of miniature inhibitory post-synaptic currents (mIPSCs) in rats' ACC slice of bee venom treatment. Taken together, the present results demonstrate an unparalleled change between excitatory and inhibitory synaptic transmission in the ACC under a state of peripheral persistent nociception that might be underlying mechanisms of the excessive excitability of the ACC neurons. We propose that the painful stimuli when lasts or becomes persistent may cause a disruption of the balance between excitatory and inhibitory synaptic transmission that can contribute to the functional change in the ACC.