Protective effect of soloxolone derivatives in carrageenan- and LPS-driven acute inflammation: Pharmacological profiling and their effects on key inflammation-related processes Full article
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Biomedicine & Pharmacotherapy
ISSN: 1950-6007 |
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| Output data | Year: 2023, Volume: 159, Pages: 114231 Pages count : 1 DOI: 10.1016/j.biopha.2023.114231 | ||||
| Tags | Inflammation, Soloxolone methyl, Cyanoenone-bearing triterpenoids, Carrageenan, Acute lung injury, Epithelial-mesenchymal transition, Apoptosis, Thrombin | ||||
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Abstract:
The anti-inflammatory potential of three cyanoenone-containing triterpenoids, including soloxolone methyl (SM), soloxolone (S) and its novel derivative bearing at the C-30 amidoxime moiety (SAO), was studied in murine models of acute inflammation. It was found that the compounds effectively suppressed the development of carrageenan-induced paw edema and peritonitis as well as lipopolysaccharide (LPS)-driven acute lung injury (ALI) with therapeutic outcomes comparable with that of the reference drugs indomethacin and dexamethasone. Non-immunogenic carrageenan-stimulated inflammation was more sensitive to the transformation of C-30 of SM compared with immunogenic LPS-induced inflammation: the anti-inflammatory properties of the studied compounds against carrageenan-induced paw edema and peritonitis decreased in the order of SAO > S > > SM, whereas the efficiency of these triterpenoids against LPS-driven ALI was similar (SAO ≈ S ≈ SM). Further studies demonstrated that soloxolone derivatives significantly inhibited a range of immune-related processes, including granulocyte influx and the expression of key pro-inflammatory cytokines and chemokines in the inflamed sites as well as the functional activity of macrophages. Moreover, SM was found to prevent inflammation-associated apoptosis of A549 pneumocytes and effectively inhibited the protease activity of thrombin (IC50 = 10.3 µM) tightly associated with rodent inflammatome. Taken together, our findings demonstrate that soloxolone derivatives can be considered as novel promising anti-inflammatory drug candidates with multi-targeted mechanism of action.
Cite:
Sen’kova A.V.
, Savin I.A.
, Odarenko K.V.
, Salomatina O.V.
, Salakhutdinov N.F.
, Zenkova M.A.
, Markov A.V.
Protective effect of soloxolone derivatives in carrageenan- and LPS-driven acute inflammation: Pharmacological profiling and their effects on key inflammation-related processes
Biomedicine & Pharmacotherapy. 2023. V.159. P.114231. DOI: 10.1016/j.biopha.2023.114231 WOS Scopus РИНЦ OpenAlex
Protective effect of soloxolone derivatives in carrageenan- and LPS-driven acute inflammation: Pharmacological profiling and their effects on key inflammation-related processes
Biomedicine & Pharmacotherapy. 2023. V.159. P.114231. DOI: 10.1016/j.biopha.2023.114231 WOS Scopus РИНЦ OpenAlex
Dates:
| Submitted: | Dec 21, 2022 |
| Accepted: | Jan 8, 2023 |
| Published online: | Jan 12, 2023 |
Identifiers:
| Web of science: | WOS:000925124200001 |
| Scopus: | 2-s2.0-85147101171 |
| Elibrary: | 60808818 |
| OpenAlex: | W4316340109 |