title: Glycyrrhizic acid and 18β-glycyrrhetinic acid modulate lipopolysaccharide-induced inflammatory response by suppression of NF-κB through PI3K p110δ and p110γ inhibitions.
abstract: The roots and rhizomes of licorice ( Glycyrrhia ) species have been used extensively as natural sweeteners and herbal medicines. The aim of this work was to determine the in vitro anti-inflammatory effects of glycyrrhizic acid (GA) and 18β-glycyrrhetinic acid (18βGA) from licorice in a lipopolysaccharide (LPS)-stimulated macrophage model. The results showed that treatment with 25-75 μM GA or 18βGA did not reduce RAW 264.7 cell viability but did significantly inhibit the production of LPS-induced nitric oxide (NO), prostaglandin E(2) (PGE(2)), and intracellular reactive oxygen species (ROS). Western blotting and reverse transcriptase polymerase chain reaction (RT-PCR) analyses revealed that GA and 18βGA significantly reduced the protein and mRNA levels of iNOS and COX-2 in LPS-induced macrophages. Both GA and 18βGA inhibited the activation of NF-κB and the activities of phosphoinositide-3-kinase (PI3K) p110δ and p110γ isoforms and then reduced the production of LPS-induced tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-1β in a dose-dependent manner. In conclusion, these results indicate that GA and 18βGA may provide an anti-inflammatory effect by attenuating the generation of excessive NO, PGE(2), and ROS and by suppressing the expression of pro-inflammatory genes through the inhibition of NF-κB and PI3K activity. Thus, the results suggest that GA and 18βGA might serve as potential agents for the treatment of inflammatory-mediated diseases.
authors.affiliation: Department of Food Science and Biotechnology, National Chung Hsing University, Taichung, Taiwan.
authors.forename: Chung-Yi
authors.initials: CY
authors.lastname: Wang
authors.forename: Tzu-Chien
authors.initials: TC
authors.lastname: Kao
authors.forename: Wen-Hsieh
authors.initials: WH
authors.lastname: Lo
authors.forename: Gow-Chin
authors.initials: GC
authors.lastname: Yen
mesh_terms: D000818:Animals; D002460:Cell Line; D058543:Class Ia Phosphatidylinositol 3-Kinase / Q000276:immunology*; D058544:Class Ib Phosphatidylinositol 3-Kinase / Q000276:immunology*; D015536:Down-Regulation / Q000187:drug effects*; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives / Q000276:immunology / Q000494:pharmacology; D006035:Glycyrrhiza / Q000737:chemistry; D019695:Glycyrrhizic Acid / Q000031:analogs & derivatives / Q000276:immunology / Q000494:pharmacology*; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D051379:Mice; D016328:NF-kappa B / Q000276:immunology*; D010936:Plant Extracts / Q000276:immunology / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D008070:Lipopolysaccharides; D016328:NF-kappa B; D010936:Plant Extracts; C119129:18alpha-glycyrrhetinic acid; D019695:Glycyrrhizic Acid; D058543:Class Ia Phosphatidylinositol 3-Kinase; D058544:Class Ib Phosphatidylinositol 3-Kinase; D006034:Glycyrrhetinic Acid