Anti-Inflammatory Mechanisms of Koreanaside A, a Lignan Isolated from the Flower of Forsythia koreana, against LPS-Induced Macrophage Activation and DSS-Induced Colitis Mice: The Crucial Role of AP-1, NF-κB, and JAK/STAT Signaling

Abstract

The current treatment options for inflammatory bowel disease (IBD) are unsatisfactory. Therefore, novel and safer therapies are needed. We previously reported that koreanaside A (KA) showed high radical scavenging activity and suppressed vascular cell adhesion molecule 1 (VCAM-1) expression in vascular smooth muscle cells. However, the molecular mechanisms involved in its anti-inflammatory effect have not been reported. KA inhibited pro-inflammatory mediators such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), nitric oxide (NO), and prostaglandin E2 (PGE2). KA inhibited the production and mRNA expression of interleukin (IL)-6 and tumor necrosis factor-α (TNF-α) induced by LPS. KA downregulated the myeloid differentiation primary response 88 (MyD88)-dependent inflammatory gene expressions in the MyD88-overexpressed cells. KA suppressed the LPS-induced transcriptional and DNA-binding activities of activator protein-1 (AP-1) and nuclear factor-kappa B (NF-κB). KA was found to inhibit the phosphorylation of Janus kinase 1/2 (JAK1/2) and signal transducers and activators of transcription 1/3 (STAT1/3). In DSS-induced colitis mice, KA relieved the symptoms of colitis by suppressing inflammatory cell infiltration, restoring tight junction (TJ)- and epithelial–mesenchymal transition (EMT)-related protein expression, and inactivating AP-1, NF-κB, and STAT1/3. Therefore, KA reduced inflammatory responses by downregulating AP-1, NF-κB, and JAK/STAT signaling in LPS-induced macrophages and DSS-induced colitis mice.

GDF3 Protects Mice against Sepsis-Induced Cardiac Dysfunction and Mortality by Suppression of Macrophage Pro-Inflammatory Phenotype

“…Hence, wild-type mice were administered with rGDF3 (10 μg/kg) or the same dose of BSA 12 h prior to LPS injection, mouse sera were collected for cytokine assays 12 h after LPS injection. ELISA results showed that serum levels of TNF-α, IL-6, and MCP-1 both were significantly increased in LPS-treated mice, compared with controls ( Figure 5A-C), which are consistent with previous reports [20]. However, pre-administration of mice with rGDF3 remarkably decreased serum levels of TNF-α, IL-6, and MCP-1 upon LPS challenge ( Figure 5A-C).…”

Disruption of FGF Signaling Ameliorates Inflammatory Response in Hepatic Stellate Cells

“…It contains sinusoidal endothelial cells, Kupffer cells, HSCs, and others ( Bottcher et al, 2018 ). Treating HSCs with proinflammatory cytokines and LPS results in the activation of proinflammatory signaling pathways, including the NF-κB pathway, and subsequent production of chemokines and cytokines ( Chen et al, 2017 ; Kim et al, 2019 ). It has been predicted that HSCs regulate inflammation during acute liver injury ( Breitkopf-Heinlein et al, 2017 ).…”

Anti-Inflammatory Activity and ROS Regulation Effect of Sinapaldehyde in LPS-Stimulated RAW 264.7 Macrophages

“…Macrophages exposed to LPS during microorganism infections stimulate the immune system to produce cytokines and chemokines, followed by inflammatory events. Thus, inhibiting macrophage activation by LPS is an important focus for therapeutic strategies aimed at treating inflammatory diseases [ 11 , 12 , 13 , 14 ].…”