Glycyrrhiza uralensis flavonoids inhibit brain microglial cell TNF-α secretion, p-IκB expression, and increase brain-derived neurotropic factor (BDNF) secretion

Abstract

ObjectiveAsthma 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. MethodsBV-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-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. ResultsASHMI produced dose-dependent inhibition of TNF-α secretion by cultured-mouse microglia 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 associated with attenuation of p-NF-κB expression, and was accompanied by increased BDNF secretion. ConclusionASHMI 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 inflammatory and anti-anxiety effects.