Columbianadin Dampens In Vitro Inflammatory Actions and Inhibits Liver Injury via Inhibition of NF-κB/MAPKs: Impacts on ∙OH Radicals and HO-1 Expression
| Autor: | Chih Wei Hsia, Shaw Min Hou, Chih Hsuan Hsia, Manjunath Manubolu, Yen Jen Chen, Thanasekaran Jayakumar, Joen Rong Sheu, Tsorng Harn Fong, Wei-Chieh Huang, Chao Chien Chang, Periyakali Saravanabhavan |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway LPS Physiology Clinical Biochemistry Pharmacology medicine.disease_cause Biochemistry Article 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine NF-κB/MAPK signaling pathways Molecular Biology Liver injury Chemistry hydroxyl radicals lcsh:RM1-950 columbianadin NF-κB Cell Biology medicine.disease IκBα liver-injury 030104 developmental biology lcsh:Therapeutics. Pharmacology 030220 oncology & carcinogenesis HO-1 expression Phosphorylation Signal transduction Cell activation Oxidative stress |
| Zdroj: | Antioxidants Antioxidants, Vol 10, Iss 553, p 553 (2021) Volume 10 Issue 4 |
| ISSN: | 2076-3921 |
| Popis: | Columbianadin (CBN), a natural coumarin isolated from Angelica decursiva, is reported to have numerous biological activities, including anticancer and platelet aggregation inhibiting properties. Here, we investigated CBN’s anti-inflammatory effect in lipopolysaccharide (LPS)-stimulated RAW 264.7 cell activation and deciphered the signaling process, which could be targeted by CBN as part of the mechanisms. Using a mouse model of LPS-induced acute liver inflammation, the CBN effects were examined by distinct histologic methods using trichrome, reticulin, and Weigert’s resorcin fuchsin staining. The result showed that CBN decreased LPS-induced expressions of TNF-α, IL-1β, and iNOS and NO production in RAW 264.7 cells and mouse liver. CBN inhibited LPS-induced ERK and JNK phosphorylation, increased IκBα levels, and inhibited NF-κB p65 phosphorylation and its nuclear translocation. Application of inhibitors for ERK (PD98059) and JNK (SP600125) abolished the LPS-induced effect on NF-κB p65 phosphorylation, which indicated that ERK and JNK signaling pathways were involved in CBN-mediated inhibition of NF-κB activation. Treatment with CBN decreased hydroxyl radical (•OH) generation and increased HO-1 expression in RAW 264.7 cells. Furthermore, LPS-induced liver injury, as indicated by elevated serum levels of liver marker enzymes (aspartate aminotransferase (AST) and alanine aminotransferase (ALT)) and histopathological alterations, were reversed by CBN. This work demonstrates the utility of CBN against LPS-induced inflammation, liver injury, and oxidative stress by targeting JNK/ERK and NF-κB signaling pathways. |
| Databáze: | OpenAIRE |
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