Luteolin Inhibits Hyperglycemia‐Induced Proinflammatory Cytokine Production and Its Epigenetic Mechanism in Human Monocytes

Abstract

Hyperglycemia is a key feature in diabetes. Hyperglycemia has been implicated as a major contributor to several complications of diabetes. High glucose levels induce the release of proinflammatory cytokines. Luteolin is a flavone isolated from celery, green pepper, perilla leaf, and chamomile tea. Luteolin has been reported to possess antimutagenic, antitumorigenic, antioxidant, and anti-inflammatory properties. In this study, we investigated the effects of luteolin on proinflammatory cytokine secretion and its underlying epigenetic regulation in high-glucose-induced human monocytes. Human monocytic (THP-1) cells were cultured under controlled (14.5 mM mannitol), normoglycemic (NG, 5.5 mM glucose), or hyperglycemic (HG, 20 mM glucose) conditions, in the absence or presence of luteolin. Luteolin (3-10 μM) was added for 48 h. While hyperglycemic conditions significantly induced histone acetylation, NF-κB activation, and proinflammatory cytokine (IL-6 and TNF-α) release from THP-1 cells, luteolin suppressed NF-κB activity and cytokine release. Luteolin also significantly reduced CREB-binding protein/p300 (CBP/p300) gene expression, as well as the levels of acetylation and histone acetyltransferase (HAT) activity of the CBP/p300 protein, which is a known NF-κB coactivator. These results suggest that luteolin inhibits HG-induced cytokine production in monocytes, through epigenetic changes involving NF-κB. We therefore suggest that luteolin may be a potential candidate for the treatment and prevention of diabetes and its complications.

Beneficial effects of celery (Apium graveolens) on metabolic syndrome: A review of the existing evidences

“…Kim et al studies determined that luteolin treatment as a natural compound found in celery, in hyperglycemic conditions, could lead to suppress cytokine release in monocytes and NF‐κB‐dependent signaling pathway, increased histone deacetylases activity, and suppressed histone acetyltransferase activity in vitro. Luteolin significantly decreased acetylation of p65 and NF‐κB activation and also reduced histone acetyltransferase (p300) expression and its interaction with NF‐κB (Kim, Lee, et al, ). In another study, superoxide dismutase (SOD), CAT, GSH‐transferase, GSH‐reductase, and GSH have been studied.…”

“…Chemokines, inflammatory cytokines, p38 mitogen-activated protein kinase, protein kinase C, reactive oxygen species, and NF-κB activity in both clinical and experimental systems may release in the face of high levels of glucose. The exchange in inflammatory genes and proteins, which is caused by hyperglycemia, plays a critical role in the progress of diabetes (Kim, Lee, & Yun, 2014). In diabetes, as a chronic metabolic disorder, the free radicals are produced in oxidative stress (Mehrzad, Devriendt, Baert, & Cox, 2014).…”

Effect of Trimeric Myricetin Rhamnoside (TMR) in Carrageenan‐induced Inflammation and Caecal Ligation and Puncture‐induced Lung Oxidative Stress in Mice

“…Flavonoids function as powerful antioxidants and antiinflammatory agents in vitro (Fu et al, 2013;Kim et al, 2014) and in vivo (Parhiz et al, 2015) and are widely sought to provide wide ranging health protection (Catarino et al, 2014). Chronic inflammation is involved in the onset and development of several pathological disturbances such as arteriosclerosis, obesity, diabetes, neurodegenerative diseases and even cancer.…”

Linarin Enriched Extract Attenuates Liver Injury and Inflammation Induced by High‐Fat High‐Cholesterol Diet in Rats

“…One of the anti-inflammation mechanisms is through inhibiting the secretion and expression of proinflammatory factors [35]. For example, the activation of NF- κ B and release of TNF- α and IL-6 in human monocytes in response to hyperglycemia were suppressed by 3–10 mM luteolin [36]. Quercetin attenuated the high-fat diet induced pancreatic histopathological damage and reduced the mRNA and protein expression of NF- κ B, IL-1 β , IL-6, and TNF- α [37].…”