Background Baicalin has a significant anti-inflammation effect and is widely used in the clinical treatment of stroke. Most of the studies of Toll-like receptor 2/4 （TLR2/4） during cerebral ischemia had defined the...Background Baicalin has a significant anti-inflammation effect and is widely used in the clinical treatment of stroke. Most of the studies of Toll-like receptor 2/4 （TLR2/4） during cerebral ischemia had defined their specific expressions in microglia in hippocampus tissue. To explore the targets of baicalin in stroke, we detected the expressions of TLR2/4 in vitro/vivo.Methods By constructing a cerebral ischemia-reperfusion model in vivo and glucose oxygen deprivation model, we successfully induced neuron damage, then added baicalin and detected expressions of TLR2/4, nuclear factor-kB （NF-kB）, tumor necrosis factor-alpha （TNFα）, and interleukin-1β （IL-1β） in mRNA level and protein level.Results We found distinct upregulations of TLR2/4 and TNFα in both mRNA level and protein level in PC12 cells and primary neurons. Moreover, TLR2/4 and TNFα expressions were significantly higher in mice hippocampus treated with cerebral ischemia-reperfusion. Baicalin could downregulate the expressions of TLR2/4 and TNFα in the damaged cells and mice hippocampus effectively.Conclusions Neurons could respond to the damage and activate the related signal pathway directly. TLR2/4 responsed to the damage and sent the signal to downstream factor TNFα through activating NF-kB. Baicalin could inhibit the inflammatory reaction in neuron damage and TLR might be its targets, which explained why baicalin could widely be used in the clinical treatment of stroke.展开更多
Brazilein is reported to have immunosuppressive effect on cardiovascular and cerebral-vascular diseases. The essential roles of innate immunity in cerebral ischemia are increasingly identified, but no studies concerni...Brazilein is reported to have immunosuppressive effect on cardiovascular and cerebral-vascular diseases. The essential roles of innate immunity in cerebral ischemia are increasingly identified, but no studies concerning the influence of brazilein on the innate immunity receptors have been reported. The present study was designed to investigate the regulation of NOD2 （Nucleotide-binding oligomerization domain-containing protein 2） by brazilein for its protection of neuron in cerebral ischemia in vivo and oxygen-glucose deprivation in vitro. The results showed that brazilein could reverse the elevated expression of NOD2 and TNFa （tumor necrosis factor alpha） elicited by cerebral ischemia and reperfusion. This reduction could also be detected in normal mice and C 17.2 cells, indicating that this suppressive effect of brazilein was correlated with NOD2. The results from GFP reporter plasmid assay suggested brazilein inhibited NOD2 gene transcription. In conclusion, brazilein could attenuate NOD2 and TNFα expression in cerebral ischemia and NOD2 may be one possible target of brazilein for its immune suppressive effect in neuro-inflammation.展开更多
Brazilein is an active small molecular compound extracted from Caesalpinia sappan L. with favorable pharmacological properties on immune system, cardiovascular system, and nervous system. C. sappan has been used as a ...Brazilein is an active small molecular compound extracted from Caesalpinia sappan L. with favorable pharmacological properties on immune system, cardiovascular system, and nervous system. C. sappan has been used as a traditional medicine in China for hundreds of years for various diseases. However, the general reproductive toxicity of brazilein is still unknown. The purpose of the present study was to thoroughly evaluate the general reproductive toxicity of brazilein in ICR mice to support the future drug development and modernization of this potent traditional Chinese medicine. The results showed that, although no apparent toxicity on the reproducibility of the male was observed, brazilein might cause considerable risks to the fetuses and females as indicated by the ratios of dead fetuses and reabsorptions. In conclusion, our results from the present study provided some useful insights about the safety profile of brazilein, suggesting that brazilein should be used with caution in pregnant women.展开更多
基金This work was supported by grants from the National Natural Science Foundation of China （No. 30973896, No. 30801523, and No. 81073092） and the National S＆T Major Special Project for New Drug R＆D Program of China （No. 2009ZX09103-301, No. 2009ZX09502, No. 2009ZX09308-003, and No. 2011ZX09101- 002-11）.Acknowledgments： We thank specially all our colleagues in our laboratory.
文摘Background Baicalin has a significant anti-inflammation effect and is widely used in the clinical treatment of stroke. Most of the studies of Toll-like receptor 2/4 （TLR2/4） during cerebral ischemia had defined their specific expressions in microglia in hippocampus tissue. To explore the targets of baicalin in stroke, we detected the expressions of TLR2/4 in vitro/vivo.Methods By constructing a cerebral ischemia-reperfusion model in vivo and glucose oxygen deprivation model, we successfully induced neuron damage, then added baicalin and detected expressions of TLR2/4, nuclear factor-kB （NF-kB）, tumor necrosis factor-alpha （TNFα）, and interleukin-1β （IL-1β） in mRNA level and protein level.Results We found distinct upregulations of TLR2/4 and TNFα in both mRNA level and protein level in PC12 cells and primary neurons. Moreover, TLR2/4 and TNFα expressions were significantly higher in mice hippocampus treated with cerebral ischemia-reperfusion. Baicalin could downregulate the expressions of TLR2/4 and TNFα in the damaged cells and mice hippocampus effectively.Conclusions Neurons could respond to the damage and activate the related signal pathway directly. TLR2/4 responsed to the damage and sent the signal to downstream factor TNFα through activating NF-kB. Baicalin could inhibit the inflammatory reaction in neuron damage and TLR might be its targets, which explained why baicalin could widely be used in the clinical treatment of stroke.
基金supported by the National S&T Major Special Project for New Drug R&D Program of China(Nos.2012ZX09102-201-008,2012ZX09103-201-041,and 2011ZX09101-002-11)National Natural Science Foundation of China(Nos.81374006 and 81073092)
文摘Brazilein is reported to have immunosuppressive effect on cardiovascular and cerebral-vascular diseases. The essential roles of innate immunity in cerebral ischemia are increasingly identified, but no studies concerning the influence of brazilein on the innate immunity receptors have been reported. The present study was designed to investigate the regulation of NOD2 （Nucleotide-binding oligomerization domain-containing protein 2） by brazilein for its protection of neuron in cerebral ischemia in vivo and oxygen-glucose deprivation in vitro. The results showed that brazilein could reverse the elevated expression of NOD2 and TNFa （tumor necrosis factor alpha） elicited by cerebral ischemia and reperfusion. This reduction could also be detected in normal mice and C 17.2 cells, indicating that this suppressive effect of brazilein was correlated with NOD2. The results from GFP reporter plasmid assay suggested brazilein inhibited NOD2 gene transcription. In conclusion, brazilein could attenuate NOD2 and TNFα expression in cerebral ischemia and NOD2 may be one possible target of brazilein for its immune suppressive effect in neuro-inflammation.
基金supported by the National Science&Technology Major Special Project for New Drug R&D Program of China(No.2012ZX09102-201-008)
文摘Brazilein is an active small molecular compound extracted from Caesalpinia sappan L. with favorable pharmacological properties on immune system, cardiovascular system, and nervous system. C. sappan has been used as a traditional medicine in China for hundreds of years for various diseases. However, the general reproductive toxicity of brazilein is still unknown. The purpose of the present study was to thoroughly evaluate the general reproductive toxicity of brazilein in ICR mice to support the future drug development and modernization of this potent traditional Chinese medicine. The results showed that, although no apparent toxicity on the reproducibility of the male was observed, brazilein might cause considerable risks to the fetuses and females as indicated by the ratios of dead fetuses and reabsorptions. In conclusion, our results from the present study provided some useful insights about the safety profile of brazilein, suggesting that brazilein should be used with caution in pregnant women.
