Anti-inflammatory effects of liquiritigenin as a consequence of the inhibition of NF-kappaB-dependent iNOS and proinflammatory cytokines production.

ABSTRACT: Glycyrrhizae radix has been widely used as a cytoprotective, plant-derived medicine. We have identified a flavanoid, liquiritigenin, as an active component in extracts of Glycyrrhizae radix. This research investigated the effects of liquiritigenin on the induction of inducible NOS (iNOS) and proinflammatory cytokines by lipopolysaccharide (LPS) in Raw264.7 cells, and on paw oedema in rats.iNOS expression was determined by western blotting, real-time reverse transcription-PCR and reporter gene analyses. Tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta and IL-6 were assayed by ELISA. Gel shift assay and immunoblotting were used to assess NF-kappaB activation. The effect of liquiritigenin on acute inflammation in vivo was evaluated using carrageenan-induced paw oedema.Treatment of Raw264.7 cells with liquiritigenin caused inhibition of LPS-induced NF-kappaB DNA binding activity, due to repression of I-kappaBalpha phosphorylation and degradation. Liquiritigenin treatment prevented LPS from increasing the levels of iNOS protein and mRNA in a concentration-dependent manner. Liquiritigenin also suppressed the production of TNF-alpha, IL-1beta and IL-6 from Raw264.7 cells after LPS. In rats, liquiritigenin treatment inhibited formation of paw oedema induced by carrageenan.These results demonstrate that liquiritigenin exerts anti-inflammatory effects, which results from the inhibition of NF-kappaB activation in macrophages, thereby decreasing production of iNOS and proinflammatory cytokines. Our findings showing inhibition by liquiritigenin of paw oedema as well as inflammatory gene induction will help to understand the pharmacology and mode of action of liquiritigenin, and of the anti-inflammatory use of Glycyrrhizae radix.

SUBMITTER: Kim YW 

PROVIDER: S-EPMC2438972 | biostudies-other | 2008 May

REPOSITORIES: biostudies-other