Elucidating the Anti-Inflammatory and Anti-Diabetic Properties of Urolithin Bioactive Metabolites from Pecan

Abstract

. Pecans are a rich source of ellagitannins which are not absorbed by humans, rather they are catabolized into urolithins by human gut microbiota and enterohepatic circulation. Urolithin A and B have been studied for their antioxidant, antimicrobial, anti-inflammatory, anticancer, and antihyperglycemic properties. This project combined a holistic approach of traditional medicine with scientific evidences. A diseased state, with proper human diet, could potentially be reversed by a combination of bioactive compounds. Polyphenols mitigate insulin resistance, obesity, inflammation, cardiovascular diseases and many others. The challenge is poor systemic bioavailability of these secondary metabolites. However, biotransformation of polyphenols by intestinal microflora conserves their functions and makes them bioavailable. The aim of this investigation was to elucidate role of oxidative stresses in anti-inflammatory effect of urolithin A and B and understand their role in a diabetic model. Urolithin A and B exerted anti-inflammatory properties in inflamed colon Caco-2 and endothelial HUVEC cells by suppressing ROS and upregulating LXR⍺. ⍺. In presence of LPS and PA and TNF ⍺ urolithin A suppressed increased levels of intracellular ROS and downregulated the pathways such as inflammation and insulin signaling in cell models. Whereas urolithin B, in a ROS independent mechanism worked in HUVEC, Caco-2 and C2C12 cells. Urolithin A and B suppressed insulin resistance induced by palmitic acid in muscle C2C12 cells and AML 12 by upregulating protein expression of pIRS and pAKT. They also downregulated the glucose production in insulin resistant hepatic AML 12 cells. Thereby, this study successfully demonstrated the multifaceted nature of urolithin A and B to ameliorate inflammation and insulin resistance in in-vitro model, key events in the scenario of the metabolic syndrome