Evogliptin Directly Inhibits Inflammatory and Fibrotic Signaling in Isolated Liver Cells

Abstract

Chronic liver inflammation can lead to fibrosis, cirrhosis, and hepatocellular carcinoma. Kupffer cells (KC) secrete proinflammatory and fibrogenic cytokines in response to lipopolysaccharide (LPS), and so play an important role in liver inflammation, where they induce hepatocellular damage. LPS also activates hepatic stellate cells and induces extracellular matrix deposition. In this study, we used isolated primary KC, primary hepatocytes, and primary hepatic stellate cells (HSC) to investigate whether evogliptin directly inhibits inflammatory and fibrotic signaling. We found that evogliptin inhibited LPS-induced secretion of inducible nitric oxide synthase and transforming growth factor β (TGF-β) from KC. Moreover, evogliptin inhibited inflammatory mediator release from hepatocytes and hepatic stellate cell activation that were induced by KC-secreted cytokines. In hepatocytes, evogliptin also inhibited LPS-induced expression of proinflammatory cytokines and fibrotic TGF-β. In addition, evogliptin inhibited TGF-β-induced increases in connective tissue growth factor levels and HSC activation. These findings indicate that evogliptin inhibits inflammatory and fibrotic signaling in liver cells. We also showed that the inhibitory effect of evogliptin on inflammatory and fibrotic signaling is associated with the induction of autophagy.

What’s New in the Treatment of Non-Alcoholic Fatty Liver Disease (NAFLD)

“…To support the need for research on the effects of DPP-4I on liver health, a study showed that evogliptin has beneficial effects in the improvement of inflammatory signaling pathways in isolated liver cells, connected with its modulation of autophagy. The above data show the potential efficiency of this group of medications in hepatic fibrosis and inflammation treatment [114].…”

Mechanism of annexin A1/N-formylpeptide receptor regulation of macrophage function to inhibit hepatic stellate cell activation through Wnt/β-catenin pathway

“…Hepatocyte injury triggers an inflammatory response, releases various cytokines and inflammatory factors, activates HSCs, and causes secretion and deposition of ECM, leading to liver fibrosis[ 26 , 27 ]. Immune cells, especially Kupffer cells and macrophages in the liver, are key regulators of inflammation[ 28 ]. Kupffer cells are intrinsic macrophages in the liver, which play an important role in the elimination of and defense against bacteria and pathogenic substances from the gastrointestinal tract[ 29 ].…”

The Effect of Evogliptin Tartrate on Controlling Inflammatory Pain

“…Evogliptin tartrate, initially designed for managing blood glucose levels in patients with type 2 diabetes, operates by inhibiting the activity of DPP-4, thereby elevating the concentrations of incretin hormones such as GLP-1 and glucose-dependent insulinotropic polypeptide [15]. These hormones assume an important role in governing glucose metabolism, and emerging research has suggested their anti-inflammatory effects [16,17]. In the current study, we observed that evogliptin tartrate effectively diminished paw thickness, heightened the pain threshold, attenuated the transmission of pain signals within nociceptive nerves, and abated inflammatory cytokines in rats with inflammation and ensuing inflammatory pain, triggered by the intraplantar subcutaneous injection of CFA into the left hind paw.…”

“…Several studies have investigated the potential anti-inflammatory effects of evogliptin tartrate in various conditions [16,17]. Seo et al suggested that treatment with evogliptin tartrate reduces the levels of inflammatory and fibrotic signaling in liver cells [17].…”