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.

Anti-Inflammatory Activities of the Ethanol Extract of Prasiola japonica, an Edible Freshwater Green Algae, and Its Various Solvent Fractions in LPS-Induced Macrophages and Carrageenan-Induced Paw Edema via the AP-1 Pathway

“…Medicinal plants with natural sources still offer promising options and are recognized as therapeutic agents. In addition, understanding the mechanisms of therapeutic action could lead to the discovery of new drugs from natural sources with reduced or no side effects [ 21 , 22 , 23 ]. The edible freshwater green algae, P. japonica , has been described to possess pharmacological benefits.…”

“…Strengthening these findings, immunoblot analyses of the level of phosphorylation of AP-1 subunits, c-jun and c-Fos, revealed that Pj-EE-CF modulates the transcriptional activation of AP-1. Previous studies reported the essential role and mechanism of MAPKs in activating AP-1 pathways [ 7 , 23 , 25 ]. Consequently, we checked signaling molecules upstream of this AP-1 activation, and Pj-EE-CF specifically inhibited ERK and p38 activation.…”

“…The phytochemical screening of Pj-EE-CF was characterized by LC-MS/MS. LC-MS/MS analyses were performed as previously described [ 23 ].…”

Caragana rosea Turcz Methanol Extract Inhibits Lipopolysaccharide-Induced Inflammatory Responses by Suppressing the TLR4/NF-κB/IRF3 Signaling Pathways

“…The bands were documented, and band intensity was measured using ImageJ software. For preparing lung lysate samples, the upper lobes of the right lungs of the mice used in the ALI experiment (see below) were collected, frozen in liquid nitrogen, and stored at −80 • C. The tissues were thawed and homogenized, and whole protein lysates were prepared as previously described [68].…”

Anti-Inflammatory Effects of Huberia peruviana Cogn. Methanol Extract by Inhibiting Src Activity in the NF-κB Pathway

“…To perform the LC-MS/MS analysis, Xevo G2-XS Q-TOF-LC/MS (Waters, Milford, MA, USA) was used as reported previously [33]. A reverse-phase BEH C18, 2.1 × 100 mm, 1.7 µm column (Waters, Milford, MA, USA) was used for UPLC.…”