Dietary Advanced Glycation Endproducts Decrease Glucocorticoid Sensitivity In Vitro

Abstract

Glucocorticoids are very effective anti-inflammatory drugs and widely used for inflammatory bowel disease (IBD) patients. However, approximately 20% of IBD patients do not respond to glucocorticoids and the reason for this is largely unknown. Dietary advanced glycation endproducts (AGEs) are formed via the Maillard reaction during the thermal processing of food products and can induce a pro-inflammatory reaction in human cells. To investigate whether this pro-inflammatory response could be mitigated by glucocorticoids, human macrophage-like cells were exposed to both LPS and AGEs to induce interleukin-8 (IL8) secretion. This pro-inflammatory response was then modulated by adding pharmacological compounds interfering in different steps of the anti-inflammatory mechanism of glucocorticoids: rapamycin, quercetin, and theophylline. Additionally, intracellular reactive oxygen species (ROS) were measured and the glucocorticoid receptor phosphorylation state was assessed. The results show that AGEs induced glucocorticoid resistance, which could be mitigated by quercetin and rapamycin. No change in the phosphorylation state of the glucocorticoid receptor was observed. Additionally, intracellular ROS formation was induced by AGEs, which was mitigated by quercetin. This suggests that AGE-induced ROS is an underlying mechanism to AGE-induced glucocorticoid resistance. This study shows for the first time the phenomenon of dietary AGE-induced glucocorticoid resistance due to the formation of ROS. Our findings indicate that food products with a high inflammatory potential can induce glucocorticoid resistance; these results may be of great importance to IBD patients suffering from glucocorticoid resistance.

Investigating the active compounds and mechanism of HuaShi XuanFei formula for prevention and treatment of COVID-19 based on network pharmacology and molecular docking analysis

“…Quercetin was reported to show virucidal activity, which could prevent or cure murine coronavirus, herpes simplex, influenza virus (H1N1/H3N2/H9N2) infection, and respiratory syncytium [40][41][42][43]. Quercetin could also reduce the production of reactive oxygen species (ROS) to mitigate the pro-inflammatory response [44]. Luteolin and chrysoeriol were revealed to show antioxidant, anti-inflammatory, antiviral, and antimicrobial activities [45].…”

Can network pharmacology identify the anti-virus and anti- inflammatory activities of Shuanghuanglian oral liquid used in Chinese medicine for respiratory tract infection?

“…Moreover, quercetin could not only influence the bioavailability of anticancer and antiviral drugs in vivo but also alleviate endotoxin-stimulated apoptosis and inflammation by up-regulation of relevant micro-RNA [41,42]. Additionally, quercetin could mitigate the intracellular formation of reactive oxygen species (ROS) to reduce the pro-inflammatory response [43]. Luteolin is proved to have significant protective effects of antivirus and anti-inflammatory in vivo.…”

Natural Antioxidants to the Rescue?

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