Dual effect of soloxolone methyl on LPS-induced inflammation in vitro and in vivo

Dual effect of soloxolone methyl on LPS-induced inflammation in vitro and in vivo Full article

Journal

International Journal of Molecular Sciences
ISSN: 1661-6596

Output data

Year: 2020, Volume: 21, Number: 21, Article number : 7876, Pages count : 35 DOI: 10.3390/ijms21217876

Tags

18βH-glycyrrhetinic acid; Anti-inflammatory activity; Carrageenan-induced peritonitis; Cytokines production; Derivatives; LPS-induced endotoxemia; Molecular docking; Soloxolone methyl; Target prediction

Authors

Markov A.V. ¹ , Se?kova A.V. ¹ , Babich V.O. ¹ , Odarenko Kirill V. ¹ , Talyshev Vadim A. ¹ , Salomatina O.V. ² , Salakhutdinov N.F. ² , Zenkova M.A. ¹ , Logashenko E.B. ¹

Affiliations

1	(Scopus) Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, 630090, Russian Federation
2	(Scopus) N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, 630090, Russian Federation

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. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.

Markov A.V. , Se?kova A.V. , Babich V.O. , Odarenko K.V. , Talyshev V.A. , Salomatina O.V. , Salakhutdinov N.F. , Zenkova M.A. , Logashenko E.B.
Dual effect of soloxolone methyl on LPS-induced inflammation in vitro and in vivo

International Journal of Molecular Sciences. 2020. V.21. N21. 7876 :1-35. DOI: 10.3390/ijms21217876 WOS Scopus РИНЦ

Full text from publisher

Published online:

Oct 23, 2020

Web of science	WOS:000589018600001
Scopus	2-s2.0-85093859369
Elibrary	45200976
OpenAlex	W3093627210