TSG (2,3,4',5-tetrahydroxystilbene 2-O-β-D-glucoside) suppresses induction of pro-inflammatory factors by attenuating the binding activity of nuclear factor-κB in microglia

Background: induction of pro-inflammatory factors is one of the characteristics of microglia activation and can be regulated by numerous active components of chinese traditional herbs. suppression of pro-inflammatory factors is beneficial to alleviate microglia-mediated cell injury. the present study aims to investigate the effect and possible mechanism of 2,3,4',5-tetrahydroxystilbene 2-o-β-d-glucoside (tsg) on lps-mediated induction of pro-inflammatory factors in microglia. methods: western blot,elisa,and hoechst 33258 were used to measure the protein expression,tnf-α/il-6 content,and apoptotic nuclei,respectively. the mrna level was measured by real time-pcr. nitric oxide (no) content,lactate dehydrogenase (ldh) content,and nf-κb binding activity were assayed by commercial kits. results: tsg reduced inos protein expression as well as tnf-α,il-6,and no content in lps-stimulated bv-2 cells. tsg attenuated the increase in apoptotic nuclei,caspase-3 cleavage,and ldh content induced by bv-2 cell-derived conditioned medium in primary hippocampal neurons. mechanistic studies showed that tsg reduced the mrna level of inos,tnf-α,and il-6. tsg failed to suppress iκb-α degradation,nf-κb phosphorylation and nuclear translocation,and erk1/2,jnk,and p38 phosphorylation. tsg,however,markedly reduced the binding of nf-κb to its dna element. chromatin immunoprecipitation (chip) assays confirmed that tsg reduced nf-κb binding to the inos promoter. these findings were ascertained in primary microglia where the lps-induced increase in inos expression,no content,apoptotic nuclei,and nf-κb binding to its dna element were diminished by tsg. conclusions: these studies demonstrate that tsg attenuates lps-mediated induction of pro-inflammatory factors in microglia through reducing the binding activity of nf-κb. this might help us to further understand the pharmacological role of tsg in inflammatory response in the central nervous system. © 2013 huang et al.; licensee biomed central ltd.