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- Title
Cissus subtetragona Planch. Ameliorates Inflammatory Responses in LPS-induced Macrophages, HCl/EtOH-induced Gastritis, and LPS-induced Lung Injury via Attenuation of Src and TAK1.
- Authors
Rahmawati, Laily; Aziz, Nur; Oh, Jieun; Hong, Yo Han; Woo, Byoung Young; Hong, Yong Deog; Manilack, Philaxay; Souladeth, Phetlasy; Jung, Ji Hwa; Lee, Woo Shin; Jeon, Mi Jeong; Kim, Taewoo; Hossain, Mohammad Amjad; Yum, Jinwhoa; Kim, Jong-Hoon; Cho, Jae Youl
- Abstract
Several Cissus species have been used and reported to possess medicinal benefits. However, the anti-inflammatory mechanisms of Cissus subtetragona have not been described. In this study, we examined the potential anti-inflammatory effects of C. subtetragona ethanol extract (Cs-EE) in vitro and in vivo, and investigated its molecular mechanism as well as its flavonoid content. Lipopolysaccharide (LPS)-induced macrophage-like RAW264.7 cells and primary macrophages as well as LPS-induced acute lung injury (ALI) and HCl/EtOH-induced acute gastritis mouse models were utilized. Luciferase assays, immunoblotting analyses, overexpression strategies, and cellular thermal shift assay (CETSA) were performed to identify the molecular mechanisms and targets of Cs-EE. Cs-EE concentration-dependently reduced the secretion of NO and PGE2, inhibited the expression of inflammation-related cytokines in LPS-induced RAW264.7 cells, and decreased NF-κB- and AP-1-luciferase activity. Subsequently, we determined that Cs-EE decreased the phosphorylation events of NF-κB and AP-1 pathways. Cs-EE treatment also significantly ameliorated the inflammatory symptoms of HCl/EtOH-induced acute gastritis and LPS-induced ALI mouse models. Overexpression of HA-Src and HA-TAK1 along with CETSA experiments validated that inhibited inflammatory responses are the outcome of attenuation of Src and TAK1 activation. Taken together, these findings suggest that Cs-EE could be utilized as an anti-inflammatory remedy especially targeting against gastritis and acute lung injury by attenuating the activities of Src and TAK1.
- Subjects
LUNG injuries; GASTRITIS; INFLAMMATION; CISSUS; LABORATORY mice; LUNGS; LIPOPOLYSACCHARIDES
- Publication
Molecules, 2021, Vol 26, Issue 19, p6073
- ISSN
1420-3049
- Publication type
Article
- DOI
10.3390/molecules26196073