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Dual Effect of Soloxolone Methyl on LPS-Induced Inflammation In Vitro and In Vivo
| Content Provider | MDPI |
|---|---|
| Author | Aleksandra, Sen’Kova Markov, Andrey Babich, Valeriya Odarenko, Kirill Talyshev, Vadim Salomatina, Oksana Salakhutdinov, Nariman Zenkova, Marina Logashenko, Evgeniya |
| Copyright Year | 2020 |
| Description | Plant-extracted triterpenoids belong to a class of bioactive compounds with pleotropic functions, including antioxidant, anti-cancer, and anti-inflammatory effects. In this work, we investigated the anti-inflammatory and anti-oxidative activities of a semisynthetic derivative of 18βH-glycyrrhetinic acid (18βH-GA), soloxolone methyl (methyl 2-cyano-3,12-dioxo-18βH-olean-9(11),1(2)-dien-30-oate, or SM) in vitro on lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and in vivo in models of acute inflammation: LPS-induced endotoxemia and carrageenan-induced peritonitis. SM used at non-cytotoxic concentrations was found to attenuate the production of reactive oxygen species and nitric oxide (II) and increase the level of reduced glutathione production by LPS-stimulated RAW264.7 cells. Moreover, SM strongly suppressed the phagocytic and migration activity of activated macrophages. These effects were found to be associated with the stimulation of heme oxigenase-1 (HO-1) expression, as well as with the inhibition of nuclear factor-κB (NF-κB) and Akt phosphorylation. Surprisingly, it was found that SM significantly enhanced LPS-induced expression of the pro-inflammatory cytokines interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) in RAW264.7 cells via activation of the c-Jun/Toll-like receptor 4 (TLR4) signaling axis. In vivo pre-exposure treatment with SM effectively inhibited the development of carrageenan-induced acute inflammation in the peritoneal cavity, but it did not improve LPS-induced inflammation in the endotoxemia model. |
| Starting Page | 7876 |
| e-ISSN | 14220067 |
| DOI | 10.3390/ijms21217876 |
| Journal | International Journal of Molecular Sciences |
| Issue Number | 21 |
| Volume Number | 21 |
| Language | English |
| Publisher | MDPI |
| Publisher Date | 2020-10-23 |
| Access Restriction | Open |
| Subject Keyword | International Journal of Molecular Sciences Integrative and Complementary Medicine 18βh-glycyrrhetinic Acid Derivatives Soloxolone Methyl Anti-inflammatory Activity Cytokines Production Lps-induced Endotoxemia Carrageenan-induced Peritonitis Target Prediction Molecular Docking |
| Content Type | Text |
| Resource Type | Article |
