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-α secretion in an animal model of asthma.We hypothesize that ASHMI and its compounds may have modulatory effects on CNS TNF-α and BDNF production.We sought to determine the effect of ASHMI and individual herb constituents on brain microglial cell TNF-α production,and identify the active compounds that suppress TNF-α and increase BDNF.Methods:BV-2 mouse microglial cells were pre-treated with ASHMI or extracts of Ganoderma lu-cidum (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-α levels in culture supernatants were measured by ELISA.The effect of active compounds on NFκB signaling pathway and on BDNF production were determined by western blotting and ELISA,respectively.Results:ASHMI produced dose-dependent inhibition of TNF-α secretion by cultured-mouse micro-glia BV2 cells.Of the three herb extracts in ASHMI,only G.uralensis significantly and dose-dependently inhibited TNF-α production.Among the 5 flavonoids isolated from G.uralensis,isoliquiritigenin was the most effective.Isoliquiritigenin suppression of TNF-α production was asso-ciated with attenuation of p-NF-κB expression,and was accompanied by increased BDNF secretion.Conclusion:ASHMI and its effective flavonoid,isoliquiritigenin,inhibited TNF-α production by LPS stimulated microglial cells and elevated BDNF levels,which may prove to have anti-CNS inflamma-tory and anti-anxiety effects.