Dual Effect of Soloxolone Methyl on LPS-Induced Inflammation In Vitro and In Vivo

Autor: Marina A. Zenkova, Evgeniya B. Logashenko, Kirill V Odarenko, Vadim A Talyshev, Valeriya O. Babich, Oksana V. Salomatina, Nariman F. Salakhutdinov, Andrey V. Markov, Aleksandra V Sen'kova
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Lipopolysaccharides
Necrosis
Lipopolysaccharide
Anti-Inflammatory Agents
target prediction
Pharmacology
Antioxidants
soloxolone methyl
lcsh:Chemistry
chemistry.chemical_compound
Mice
18βH-glycyrrhetinic acid
Cell Movement
LPS-induced endotoxemia
carrageenan-induced peritonitis
anti-inflammatory activity
lcsh:QH301-705.5
Spectroscopy
chemistry.chemical_classification
NF-kappa B
General Medicine
Glutathione
Computer Science Applications
medicine.symptom
Pentacyclic Triterpenes
Cell Survival
cytokines production
Inflammation
Peritonitis
Nitric Oxide
Catalysis
Article
Nitric oxide
Inorganic Chemistry
In vivo
medicine
Animals
Physical and Theoretical Chemistry
Molecular Biology
Reactive oxygen species
Macrophages
Organic Chemistry
Membrane Proteins
molecular docking
Macrophage Activation
Endotoxemia
Disease Models
Animal
RAW 264.7 Cells
chemistry
lcsh:Biology (General)
lcsh:QD1-999
TLR4
derivatives
Glycyrrhetinic Acid
Reactive Oxygen Species
Proto-Oncogene Proteins c-akt
Heme Oxygenase-1
Zdroj: International Journal of Molecular Sciences, Vol 21, Iss 7876, p 7876 (2020)
International Journal of Molecular Sciences
Volume 21
Issue 21
ISSN: 1661-6596
1422-0067
Popis: 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 18&beta
H-glycyrrhetinic acid (18&beta
H-GA), soloxolone methyl (methyl 2-cyano-3,12-dioxo-18&beta
H-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-&kappa
B (NF-&kappa
B) 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-&alpha
(TNF-&alpha
), and interleukin-1&beta
(IL-1&beta
) 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.
Databáze: OpenAIRE
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