Objective:Asthma sufferers exhibit high prevalence of anxiety/depression.Elevated tumor-necrosis factor-alpha(TNF-α)levels in peripheral system and central nervous system(CNS)are associated with anxiety/depression,wh...Objective:Asthma sufferers exhibit high prevalence of anxiety/depression.Elevated tumor-necrosis factor-alpha(TNF-α)levels in peripheral system and central nervous system(CNS)are associated with anxiety/depression,whereas brain-derived neurotropic factor(BDNF)has anti-depressant effects.An anti-asthma herbal medicine intervention ASHMI inhibits peripheral TNF-αsecretion in an animal model of asthma.We hypothesize that ASHMI and its compounds may have modulatory effects on CNS TNF-αand BDNF production.We sought to determine the effect of ASHMI and individual herb constituents on brain microglial cell TNF-αproduction,and identify the active compounds that suppress TNF-αand increase BDNF.Methods:BV-2 mouse microglial cells were pre-treated with ASHMI or extracts of Ganoderma lucidum(G.lucidum),Sophora flavescens Ait(S.flavescens),and Glycyrrhiza uralensis Fischer(G.uralensis),the herbal constituents in ASHMI,or individual compounds isolated from G.uralensis at different concentrations and then stimulated with LPS.TNF-αlevels in culture supernatants were measured by ELISA.The effect of active compounds on NFkB signaling pathway and on BDNF production were determined by western blotting and ELISA,respectively.Results:ASHMI produced dose-dependent inhibition of TNF-αsecretion by cultured-mousemicroglia BV2 cells.Of the three herb extracts in ASHMI,only G.uralensis significantly and dosedependently inhibited TNF-αproduction.Among the 5 flavonoids isolated from G.uralensis,isoliquiritigeninwas themost effective.Isoliquiritigenin suppression of TNF-αproduction was associated with attenuation of p-NF-kB expression,andwas accompanied by increased BDNF secretion.Conclusion:ASHMI and its effective flavonoid,isoliquiritigenin,inhibited TNF-αproduction by LPS stimulatedmicroglial cells and elevated BDNF levels,which may prove to have anti-CNS inflammatory and anti-anxiety effects.展开更多
基金This work was supported by NIH/NCCAM center grants#P01 AT002647-0101“Center for Chinese Herbal Therapy(CHT)for Asthma”,the Sean Parker Foundation for(ASHMI Active Compounds for Asthma Therapy),and the Winston Wolkoff Fund for Integrative Medicine for Allergies and Wellness to XM Li.
文摘Objective:Asthma sufferers exhibit high prevalence of anxiety/depression.Elevated tumor-necrosis factor-alpha(TNF-α)levels in peripheral system and central nervous system(CNS)are associated with anxiety/depression,whereas brain-derived neurotropic factor(BDNF)has anti-depressant effects.An anti-asthma herbal medicine intervention ASHMI inhibits peripheral TNF-αsecretion in an animal model of asthma.We hypothesize that ASHMI and its compounds may have modulatory effects on CNS TNF-αand BDNF production.We sought to determine the effect of ASHMI and individual herb constituents on brain microglial cell TNF-αproduction,and identify the active compounds that suppress TNF-αand increase BDNF.Methods:BV-2 mouse microglial cells were pre-treated with ASHMI or extracts of Ganoderma lucidum(G.lucidum),Sophora flavescens Ait(S.flavescens),and Glycyrrhiza uralensis Fischer(G.uralensis),the herbal constituents in ASHMI,or individual compounds isolated from G.uralensis at different concentrations and then stimulated with LPS.TNF-αlevels in culture supernatants were measured by ELISA.The effect of active compounds on NFkB signaling pathway and on BDNF production were determined by western blotting and ELISA,respectively.Results:ASHMI produced dose-dependent inhibition of TNF-αsecretion by cultured-mousemicroglia BV2 cells.Of the three herb extracts in ASHMI,only G.uralensis significantly and dosedependently inhibited TNF-αproduction.Among the 5 flavonoids isolated from G.uralensis,isoliquiritigeninwas themost effective.Isoliquiritigenin suppression of TNF-αproduction was associated with attenuation of p-NF-kB expression,andwas accompanied by increased BDNF secretion.Conclusion:ASHMI and its effective flavonoid,isoliquiritigenin,inhibited TNF-αproduction by LPS stimulatedmicroglial cells and elevated BDNF levels,which may prove to have anti-CNS inflammatory and anti-anxiety effects.
