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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.


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.

SUBMITTER: Rahmawati L 

PROVIDER: S-EPMC8512965 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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<i>Cissus subtetragona</i> Planch. Ameliorates Inflammatory Responses in LPS-induced Macrophages, HCl/EtOH-induced Gastritis, and LPS-induced Lung Injury via Attenuation of Src and TAK1.

Rahmawati Laily L   Aziz Nur N   Oh Jieun J   Hong Yo Han YH   Woo Byoung Young BY   Hong Yong Deog YD   Manilack Philaxay P   Souladeth Phetlasy P   Jung Ji Hwa JH   Lee Woo Shin WS   Jeon Mi Jeong MJ   Kim Taewoo T   Hossain Mohammad Amjad MA   Yum Jinwhoa J   Kim Jong-Hoon JH   Cho Jae Youl JY  

Molecules (Basel, Switzerland) 20211008 19


Several <i>Cissus</i> species have been used and reported to possess medicinal benefits. However, the anti-inflammatory mechanisms of <i>Cissus subtetragona</i> have not been described. In this study, we examined the potential anti-inflammatory effects of <i>C. subtetragona</i> 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 L  ...[more]

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