Glycyrrhizic Acid and 18β-Glycyrrhetinic Acid Modulate Lipopolysaccharide-Induced Inflammatory Response by Suppression of NF-κB through PI3K p110δ and p110γ Inhibitions

• Published in: Journal of agricultural and food chemistry 2011-07, Vol.59 (14), p.7726-7733
• Main Authors: Wang, Chung-Yi, Kao, Tzu-Chien, Lo, Wen-Hsieh, Yen, Gow-Chin
• Format: Article
• Language: English
• Subjects: Animals; Bioactive Constituents; Biological and medical sciences; Cell Line; Class Ia Phosphatidylinositol 3-Kinase - immunology; Class Ib Phosphatidylinositol 3-Kinase - immunology; Down-Regulation - drug effects; Food industries; Fundamental and applied biological sciences. Psychology; Glycyrrhetinic Acid - analogs & derivatives; Glycyrrhetinic Acid - immunology; Glycyrrhetinic Acid - pharmacology; Glycyrrhiza - chemistry; Glycyrrhizic Acid - analogs & derivatives; Glycyrrhizic Acid - immunology; Glycyrrhizic Acid - pharmacology; Inflammation - drug therapy; Inflammation - immunology; Lipopolysaccharides - immunology; Macrophages - drug effects; Macrophages - immunology; Mice; NF-kappa B - immunology; Plant Extracts - immunology; Plant Extracts - pharmacology; Signal Transduction - drug effects
• ISSN: 0021-8561; 1520-5118
• DOI: 10.1021/jf2013265

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 E2 (PGE2), 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, PGE2, 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.