Flavonoids derived from liquorice suppress murine macrophage activation by up-regulating heme oxygenase-1 independent of Nrf2 activation

Rui Wang, Cheng Yue Zhang, Li Ping Bai, Hu Dan Pan, Li Min Shu, Ah Ng Tony Kong, Elaine Lai Han Leung, Liang Liu, Ting Li

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

Liquiritigenin (LQG), isoliquiritin (ILQ) and isoliquiritigenin (ILG) are flavonoids derived from liquorice and all possess a similar chemical structural backbone. In the current study, we found that ILQ and ILG had suppressive effects on lipopolysaccharide (LPS)-induced inflammatory responses in murine macrophage by suppressing the iNOS and COX-2 proteins and mRNA expression. A mechanistic study indicated that the effect was associated with an induction of antioxidant and detoxification enzymes, including UGT1A1, NQO1, and heme oxygenase-1 (HO-1) mRNA expression. The regulator of these enzymes, nuclear factor-erythroid 2-related factor 2 (Nrf2), which plays a critical role in LPS-induced inflammatory responses, could be activated by ILQ and ILG. Additionally, ILQ and ILG promoted Nrf2 signaling activation by inhibiting the Kelch-like ECH-associated protein 1 (Keap1) and increasing Nrf2 translocation, inducing the expression of these antioxidant enzymes. We further found that ILQ and ILG induced HO-1 expression independent of Nrf2 expression. With respect to the effect of these compounds on NF-κB signaling, ILG was found to markedly inhibit IκBα degradation and phosphorylation, while LQG and ILQ had no significant effects. These results indicate that there are correlations between the anti-inflammatory responses and the chemical structural properties of these flavonoids.

Original languageEnglish (US)
Pages (from-to)917-924
Number of pages8
JournalInternational Immunopharmacology
Volume28
Issue number2
DOIs
StatePublished - Oct 2015

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Pharmacology

Keywords

  • HO-1
  • Isoliquiritigenin
  • Isoliquiritin
  • Liquiritigenin
  • Nrf2

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