Esculetin reverses histone H2A/H2B ubiquitination, H3 dimethylation, acetylation and phosphorylation in preventing type 2 diabetic cardiomyopathy

Insulin sensitizing and cardioprotective effects of Esculetin and Telmisartan combination by attenuating Ang II mediated vascular reactivity and cardiac fibrosis

“…Briefly, the rats were allocated to two dietary regimens: Normal control (NC); fed with normal pellet diet (NPD, n¼ 6) and insulin resistant group; fed with HFD (n ¼24) ad libitum for six weeks, respectively. Recently, we have studied Esculetin at two doses (50 and 100 mg/kg/day) against cardiovascular dysfunction associated with IR and type 2 diabetes and it showed batter cardiovascular protective effect at 100 mg/kg/day dose (Kadakol et al, 2015a(Kadakol et al, , 2015b. Hence, in the present study we have used lower dose of Esculetin (50 mg/kg/day) to evaluate its additive effect with combination of Telmisartan in prevention of IR and associated cardiac fibrosis.…”

“…Insulin was estimated by ultra-sensitive rat insulin kit (Kadakol et al, 2015a(Kadakol et al, , 2015b.…”

“…Histopathology and immunohistochemistry were performed as per the protocol described earlier (Kadakol et al, 2015a(Kadakol et al, , 2015b. In brief, heart tissue samples from each rat were collected and fixed in 10% (v/v) formalin in phosphate buffered saline and embedded in paraffin.…”

“…For each group at least 25 sections were observed under Olympus BX41 microscope (Melville, NY, USA) and images were captured. The images were analyzed semi-quantitative by using Image J software for measurement of % extracellular matrix (ECM) accumulation (PSR) and % DAB positive area (IHC) and final data were analyzed by GraphPad 5 Prism software (Kadakol et al, 2015b).…”

“…Esculetin also shows a potential therapeutic role in cancer (Cho et al, 2015), obesity (Kim and Lee, 2015;Sim et al, 2015), and diabetes (Surse et al, 2011). Recently, we have reported that Esculetin shows cardioprotective effect by reversing post translational histone modifications associated with IR and type 2 diabetes (Kadakol et al, 2015b). We have also demonstrated that Esculetin improved vascular responsiveness and reduced the expression of Ang II receptors in thoracic aorta of hyperglycaemic and hyperinsulinemic rats (Kadakol et al, 2015a).…”