In the present study, we aimed to investigate the effects of Xiao-Xu-Ming decoction extract(XXM) on lipopolysaccaride(LPS)-induced neuroinflammation in vitro and in vivo. In vitro, the microglia BV2 cells were treated...In the present study, we aimed to investigate the effects of Xiao-Xu-Ming decoction extract(XXM) on lipopolysaccaride(LPS)-induced neuroinflammation in vitro and in vivo. In vitro, the microglia BV2 cells were treated with 200 ng/mL LPS for 24 h to induce inflammatory responses. In vivo, mice were treated with 5 mg/kg LPS to induce inflammatory responses. The NO level was determined by Griess Reagents. The levels of IL-1β, IL-6, TNF-α and MCP-1 were determined by ELISA. The expressions of Iba-1, TLR4 and MyD88 at the protein levels were determined by Western blotting analysis. The mRNA levels of TLR4 and MyD88 were determined by real-time PCR. In vitro, XXM significantly reduced the levels of various pro-inflammatory factors, including NO, IL-1β, IL-6 and TNF-α, induced by LPS in the supernatant of BV2 cells and suppressed expressions of inflammatory proteins TLR4 and MyD88 induced by LPS in BV2 cells. In vivo, XXM significantly inhibited microglia activation, attenuated LPS-induced inflammatory factors and chemokine production, such as IL-1β, IL-6, TNF-α and MCP-1, and inhibited the expressions of inflammatory proteins including TLR4 and MyD88, in the cortex of LPS-induced mice. Our findings suggested that XXM could attenuate LPS-induced neuroinflammation via down-regulating TLR4/MyD88 signaling pathway.展开更多
Stroke is a major cause of severe disability and death.Xiao-Xu-Ming decoction(XXMD)is an effective prescription for stroke and its sequelae,while its effective ingredients and mechanism are still unclear.In the presen...Stroke is a major cause of severe disability and death.Xiao-Xu-Ming decoction(XXMD)is an effective prescription for stroke and its sequelae,while its effective ingredients and mechanism are still unclear.In the present study,we aimed to explore the effective ingredients and mechanism of XXMD in treating cerebral ischemia using network pharmacology.The main chemical components and targets of 12 herbs of XXMD were obtained by the TCMSP database and analysis platform database.The active components in XXMD were screened according to oral utilization and drug-like properties.Then,the cerebral ischemia targets were obtained through GeneCards,OMIM,TTD,Diligent and Drugbank databases.We analyzed the pathophysiological processes and pathways involved in the treatment of cerebral ischemia with XXMD by using the Metascape data analysis platform.Results showed thatβ-sitosterol,kaempferol,quercetin,stigmasterol,wogonin,and catechins might be the potential core active ingredients of XXMD in the treatment of cerebral ischemia.The therapeutic effect of XXMD on stroke was mainly exerted through regulating neuroinflammatory response and neurovascular protection.Furthermore,the anti-neuroinflammation and neurovascular protection of XXMD were further confirmed using cerebral ischemia rats.Collectively,our findings revealed that the mechanism of XXMD on the treatment of cerebral ischemia was related to anti-neuroinflammation and neurovascular protection.展开更多
基金The National Natural Science Foundation of China(Grant No.81473383)the Innovation Fund for Graduate of Beijing Union Medical College(Grant No.2017-1007-02)+1 种基金the Drug Innovation Major Project(Grant No.2018ZX09711001-003-019)the Medical and Health Innovation Project of Chinese Academy of Medical Sciences(Grant No.2016-I2M-3-007,2018-1007-04)
文摘In the present study, we aimed to investigate the effects of Xiao-Xu-Ming decoction extract(XXM) on lipopolysaccaride(LPS)-induced neuroinflammation in vitro and in vivo. In vitro, the microglia BV2 cells were treated with 200 ng/mL LPS for 24 h to induce inflammatory responses. In vivo, mice were treated with 5 mg/kg LPS to induce inflammatory responses. The NO level was determined by Griess Reagents. The levels of IL-1β, IL-6, TNF-α and MCP-1 were determined by ELISA. The expressions of Iba-1, TLR4 and MyD88 at the protein levels were determined by Western blotting analysis. The mRNA levels of TLR4 and MyD88 were determined by real-time PCR. In vitro, XXM significantly reduced the levels of various pro-inflammatory factors, including NO, IL-1β, IL-6 and TNF-α, induced by LPS in the supernatant of BV2 cells and suppressed expressions of inflammatory proteins TLR4 and MyD88 induced by LPS in BV2 cells. In vivo, XXM significantly inhibited microglia activation, attenuated LPS-induced inflammatory factors and chemokine production, such as IL-1β, IL-6, TNF-α and MCP-1, and inhibited the expressions of inflammatory proteins including TLR4 and MyD88, in the cortex of LPS-induced mice. Our findings suggested that XXM could attenuate LPS-induced neuroinflammation via down-regulating TLR4/MyD88 signaling pathway.
基金National Natural Science Foundation of China(Gr ant No.81473383)the Medical and Health Innovation Project o Chinese Academy of Medical Sciences(Grant No.2016-I2M-3-007)Innovation Fund for Graduate of Beijing Union Medical College(Grant No.2018-1007-04)。
文摘Stroke is a major cause of severe disability and death.Xiao-Xu-Ming decoction(XXMD)is an effective prescription for stroke and its sequelae,while its effective ingredients and mechanism are still unclear.In the present study,we aimed to explore the effective ingredients and mechanism of XXMD in treating cerebral ischemia using network pharmacology.The main chemical components and targets of 12 herbs of XXMD were obtained by the TCMSP database and analysis platform database.The active components in XXMD were screened according to oral utilization and drug-like properties.Then,the cerebral ischemia targets were obtained through GeneCards,OMIM,TTD,Diligent and Drugbank databases.We analyzed the pathophysiological processes and pathways involved in the treatment of cerebral ischemia with XXMD by using the Metascape data analysis platform.Results showed thatβ-sitosterol,kaempferol,quercetin,stigmasterol,wogonin,and catechins might be the potential core active ingredients of XXMD in the treatment of cerebral ischemia.The therapeutic effect of XXMD on stroke was mainly exerted through regulating neuroinflammatory response and neurovascular protection.Furthermore,the anti-neuroinflammation and neurovascular protection of XXMD were further confirmed using cerebral ischemia rats.Collectively,our findings revealed that the mechanism of XXMD on the treatment of cerebral ischemia was related to anti-neuroinflammation and neurovascular protection.
