Synthesis and anti-inflammatory activities of glycyrrhetinic acid derivatives containing disulfide bond.
Bioorg Chem
; 119: 105542, 2022 02.
Article
en En
| MEDLINE
| ID: mdl-34902645
ABSTRACT
A series of glycyrrhetinic acid (GA, aglycone of glycyrrhizic acid) derivatives containing disulfide bond were synthesized and their anti-inflammatory and anti-fibrosis activities were evaluated in vivo and in vitro. Among them, compound 7 displayed the highest toxicity to all the tested cell lines including macrophages. Compounds 3 and 4 showed higher activities than GA in the cell and animal model. In the anti-inflammatory tests, compounds 3 and 4 down-regulated the expressions of several inflammatory factors, such as HMGB1, TLR4, IL-1ß, TNF-α and TGF-ß1 in LPS-treated RAW264.7 cells in a dose-dependent manner. Compounds 3 and 4 at 30 µM respectively reduced the levels of HMGB1 in the LPS group to 42.7% and 38.2%. In addition, the level of TLR4 decreased to close to that of control group when treated by compound 4 at the concentration of 30 µM. In the process of anti-fibrosis tests using TGF-ß1-induced A549 cell line as the model, compounds 3 and 4 also decreased the expression levels of Col1 and α-SMA in a dose-dependent manner. Compound 3 and 4 at 30 µM respectively reduced the expression of α-SMA level by 2.2-fold and 2.6-fold compared to the TGF-ß1-treated control group. Moreover, they influenced the ROS level and mitochondrial membrane potential (MMP) in A549 cells. In the paraquat-induced pulmonary fibrosis mice model, the symptoms of inflammation and fibrosis of mice were alleviated after administration of compound 3 or 4. The above results suggest that compounds 3 and 4 may be promising candidates for inflammation and lung fibrosis treatment.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Antiinflamatorios no Esteroideos
/
Disulfuros
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Ácido Glicirretínico
Tipo de estudio:
Prognostic_studies
Límite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Bioorg Chem
Año:
2022
Tipo del documento:
Article
País de afiliación:
China