Synergistic cardioptotection by tilianin and syringin in diabetic cardiomyopathy involves interaction of TLR4/NF- κB/NLRP3 and PGC1a/SIRT3 pathways

Int Immunopharmacol. 2021 May 7;96:107728. doi: 10.1016/j.intimp.2021.107728. Online ahead of print.ABSTRACTDiabetic cardiomyopathy (DCM) is a chronic multifactorial complication of type-2 diabetes mellitus, leading to heart failure. A combination of multifaceted therapeutics for the management of DCM is needed. Here, we investigated the combined effect of syringin and tilianin on DCM by evaluating cardiac function, inflammation, oxidative stress, apoptosis and mitochondrial function, and explored the contribution of TLR4/NF-κB/NLRP3 and PGC1α/SIRT3 pathways in diabetic rats and hyperglycemic-H9c2 cells. Syringin and tilianin (50 and 60 mg/kg, i.p, respectively) were administered for eight weeks, individually or in combination, to healthy and type-2 diabetic Sprague-Dawley rats. Myocardial function was recorded using a carotid catheter, mitochondrial and histopathological changes were evaluated by fluorometric and staining methods, cardiac markers and signaling pathways' proteins expression were measured through ELISA and immunoblotting. In comparison to individual treatments, combination of syringin and tilianin effectively exerted antidiabetic effects and improved cardiac function and DCM markers, reduced NLRP3/IL-6/IL-1β/TNF-α expression, and suppressed diabetes/hyperglycemia‑induced oxidative stress in rats' heart and H9c2 cells, as demonstrated by decreased 8-isoprostane, and increased superoxide dismutase-2 levels. Mitochondrial membrane depolarization and ROS pro...
Source: International Immunopharmacology - Category: Allergy & Immunology Authors: Source Type: research