crocin and Diabetic-Cardiomyopathies

Diabetic cardiomyopathy is diagnosed by the development of abnormality in the structure and performance of myocardium in diabetic mellitus (DM) patients. Recent studies reported the association between altered gut microbiota and metabolic disorders like diabetes and cardiovascular diseases. Here, we aimed to investigate the gut-heart axis in an experimental animal model where we developed a novel therapeutic combination of dapagliflozin, crocin prebiotic and Lactobacilli probiotic to correct induced diabetic cardiomyopathy.. Diabetes mellitus was induced by Intraperitoneal (i.p) streptozotocin in male rats. The experimental design includes the administration of the tested drugs (Crocin, Dapagliflozin) solely and with Lactobacillus, or in combination therapy with and without Lactobacillus to the diabetic rats for six weeks. Clinical and microscopic evaluation scoring for cardiac tissues were determined. Biochemical markers including blood glucose level, adiponectin, resistin, cardiac injury markers, lipid profile, antioxidant enzymes, pro and anti-inflammatory markers were assessed. In addition, quantitative relative expression of PPARγ and TXINP genes and capsase-3 levels were measured. The change in the microbiota abundance was investigated using real-time PCR.. This study demonstrated the synergistic effect of the triple combination; dapagliflozin, crocin prebiotic, and Lactobacillus fermentum and Lactobacillus delbrueckii probiotic in treating diabetic cardiomyopathy in rats. The triple combination significantly reduced the oxidative, inflammatory, apoptotic activities induced by streptozotocin STZ and helped in restoring the symbiotic gut microbiota.. It is worthy to perform this study in clinical trials as a primary step to include crocin and Lactobacilli in the therapeutic protocols of diabetic cardiomyopathy.

Topics: Animals; Benzhydryl Compounds; Carotenoids; Diabetes Mellitus, Experimental; Diabetic Cardiomyopathies; Gastrointestinal Microbiome; Glucosides; Lactobacillus; Male; Oxidative Stress; PPAR gamma; Rats; Rats, Wistar; Streptozocin

The association of diabetes mellitus (DM) and poor metabolic control with high incidence of cardiovascular diseases is well established. The aim of this study was to investigate the potential cardioprotective effect of crocin (Crocus sativus L. extract) on diabetic heart dysfunction and to elucidate the mediating molecular mechanisms.. Streptozotocin (STZ)-induced diabetic rats were treated with two different concentrations of crocin (10 or 20 mg/kg), while isolated cardiac myocytes exposed to 25 mM glucose, were treated with 1 or 10 μM of crocin. Treatment of STZ-diabetic rats with crocin resulted in normalization of plasma glucose levels, inhibition of cardiac hypertrophy and fibrosis, and improvement of cardiac contractile function. Heat Shock Response was enhanced. Myocardial AMPK phosphorylation was increased after treatment with crocin, resulting in normalization of autophagy marker proteins (LC3BII/LC3BI ratio, SQSTM1/p62 and Beclin-1), while the diabetes-induced myocardial apoptosis was decreased. Similar results regarding the effect of crocin on autophagy and apoptosis pathways were obtained in isolated cardiac myocytes exposed to high concentration of glucose.. The results suggest that crocin improves the deteriorated cardiac function in diabetic animals by enhancing the heat shock response, inhibiting apoptosis and normalizing autophagy in cardiac myocytes. Thus, treatment with crocin may represent a novel approach for treating diabetic cardiomyopathy.

Topics: Animals; Apoptosis; Apoptosis Regulatory Proteins; Autophagy; Autophagy-Related Proteins; Blood Glucose; Carotenoids; Diabetes Mellitus, Experimental; Diabetic Cardiomyopathies; HSP70 Heat-Shock Proteins; Male; Myocytes, Cardiac; Rats, Wistar; Recovery of Function; Signal Transduction; Streptozocin; Ventricular Function, Left; Ventricular Remodeling

Background Oxidative stress plays a critical role in the pathogenesis and progression of type 2 diabetes and diabetic-associated cardiovascular complications. This study investigated the impact of crocin combined with voluntary exercise on heart oxidative stress indicator in high-fat diet-induced type 2 diabetic rats. Materials and methods Rats were divided into four groups: diabetes, diabetic-crocin, diabetic-voluntary exercise, diabetic-crocin-voluntary exercise. Type 2 diabetes was induced by high-fat diet (4 weeks) and injection of streptozotocin (intraperitoneally, 35 mg/kg). Animals received crocin orally (50 mg/kg); voluntary exercise was performed alone or combined with crocin treatment for 8 weeks. Finally, malondialdehyde (MDA), activity of antioxidant enzymes, superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) were measured spectrophotometrically. Results Treatment of diabetic rats with crocin and exercise significantly decreased the levels of MDA (p < 0.001) and increased the activity of SOD, GPx, and CAT compared with the untreated diabetic group. In addition, combination of exercise and crocin amplified their effect on antioxidant levels in the heart tissue of type 2 diabetic rats. Conclusion We suggest that a combination of crocin with voluntary exercise treatment may cause more beneficial effects in antioxidant defense system of heart tissues than the use of crocin or voluntary exercise alone.

Topics: Animals; Antioxidants; Carotenoids; Catalase; Combined Modality Therapy; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Diabetic Cardiomyopathies; Diet, High-Fat; Exercise Therapy; Glutathione Peroxidase; Lipid Peroxidation; Male; Malondialdehyde; Myocardium; Oxidative Stress; Rats, Wistar; Streptozocin; Superoxide Dismutase