Umbelliferone attenuates diabetic cardiomyopathy by suppression of JAK/STAT signaling pathway through amelioration of oxidative stress and inflammation in rats

Abstract

AbstractUmbelliferone (UMB), 7‐hydroxycoumarin, is a naturally occurring coumarin derivative that has a plethora of biological and therapeutic activities. The focus of this research was to elucidate the curative effects of two different doses of UMB on diabetic cardiomyopathy (DCM) in a type 2 diabetic rat model induced by 50 mg/kg body weight of streptozotocin (STZ). Diabetic rats orally received 10 or 30 mg/kg of UMB daily for 8 weeks. Compared to the nontreated diabetic group, both UMB treatment doses significantly decreased glucose levels, glycated hemoglobin (HbA1c), tumor necrosis factor alpha (TNF‐α), interleukin‐6 (IL‐6), creatine kinase MB (CK‐MB), cardiovascular risk indices, and oxidative stress by reducing malondialdehyde (MDA) and increasing the activity of the antioxidant enzymes. The hypercholesterolemia and hypertriglyceridemia also dramatically decreased in diabetic groups with UMB treatments accompanied by an improvement in insulin, and insulin sensitivity indices (HOMA‐IR and QUICKI). Furthermore, the cardiac gene expressions and protein levels of Janus kinase2 (JAK2), signal transducer and activator of transcription3 (STAT3), and transforming growth factor beta1 (TGF‐β1) were also markedly downregulated in a dose‐dependent manner by UMB treatments. Finally, the biochemical results were assured by the reduction of histological alterations in cardiac tissues. In conclusion, UMB is a propitious substance for the treatment of DCM by virtuousness of its antihyperglycemic, antihyperlipidemic, antioxidant, and anti‐inflammatory properties through modulating the JAK/STAT signaling pathway that may be the underlying mechanism in UMB action.