Skimmin protects diabetic cardiomyopathy in streptozotocin‐induced diabetic rats

Abstract

Skimmin, a natural coumarin derivate, has been showed to be protective against experimental diabetic nephropathy; however, its protective effect on diabetic cardiomyopathy (DCM) is not clarified. By using in vitro and in vivo models, we investigated skimmin's protective effect on impaired heart tissues in DCM. DCM was induced by streptozotocin (STZ, 60 mg/kg) using Sprague Dawley rats, and diabetic rats were treated with either skimmin (15 or 30 mg/kg) or the vehicle for 16 weeks, and normal rats were used as a control. Hematoxylin and eosin and Masson's trichrome staining were performed to evaluate the cardiac histopathology, and the oxidative stress and proinflammation cytokines in heart tissues were measured. The protein levels of key mediators in fibrosis, pyroptosis, and autophagy in heart tissues were investigated using western blotting. In vitro, primary neonatal cardiomyocytes were treated with skimmin (2 and 10 μM) under stimulation by high glucose (30 mM) and low glucose (5 mM) respectively, and the molecular mechanisms on pyroptosis and autophagy were studied. Compared to the vehicle‐treated DCM group, skimmin treatment significantly improved the ejection fraction and fractional shortening of the left ventricle and reduced the oxidative stress by increasing the glutathione level and activity of superoxide dismutase and catalase. Skimmin also reduced cardiac fibrosis, and decreased proinflammation cytokines in cardiac tissues. Mechanism studies showed skimmin may enhance the autophagy and ameliorate NLRP3 inflammasome activation to play a protective role in DCM. This study, for the first time, indicates that skimmin might be a promising lead compound for DCM.

Comparative metabolomics analysis of different sesame (Sesamum indicum L.) tissues reveals a tissue-specific accumulation of metabolites

“…These suggest that the sesamin accumulation in sesame leaves might be influenced by the genotype and growing conditions. Sesaminol, a potent therapeutic lignan [ 15 ], and skimmin, an anti-diabetes coumarin [ 56 ], were detected both in all the tissues but in relatively high quantity in leaves followed by fresh carpels. The distribution of sesaminol suggests its possible involvement in sesame plant defense mechanisms or oxidative stress modulation.…”

Pyroptosis and Its Regulation in Diabetic Cardiomyopathy

“…It can reduce blood glucose and improve fibrosis in diabetic rats. Of note, skimmin enhances autophagy, which diminishes ROS generation and inflammatory reaction in a diabetic heart with decreased pyroptosis-related cytokines ( Liang et al, 2021 ). Skimmin could serve as a promising protective medicine in DbCM.…”

Fucoxanthin ameliorated myocardial fibrosis in STZ-induced diabetic rats and cell hypertrophy in HG-induced H9c2 cells by alleviating oxidative stress and restoring mitophagy

“…The rats were assigned to the normal control group (n = 8) and the diabetic model group (n = 24), which was induced with an intraperitoneal injection of fresh STZ (60 mg kg −1 ). The rats with FBG ≥ 16.7 mmol L −1 were considered as diabetic rats, 22,23 which is recognized as being highly similar to the type 1 diabetes model. The diabetic rats were randomized into the administration group (n = 8) to receive FX (200 mg per kg daily i.g.)…”