Therapeutic potential of oxymatrine in impeding the cardiomyopathy in the STZ- nicotinamide induced diabetes through SIRT1/Nrf2 signaling activation

Author:

Seksaria Sanket1,Mehan Sidharth1,Dutta Bhaskar Jyoti1,Gupta Ghanshyam Das1,Singh Amrita1

Affiliation:

1. ISF College of Pharmacy

Abstract

Abstract Aims Diabetes mellitus increases the risk of heart failure independently of underlying hypertention and ischemic heart disease, leads to the cardiomyopathy. Molecular mechanism underlying these pathological changes in the diabetic cardiomyopathy (DCM) are most likely to multifactorial, but clearer pathogenesis is partially understood. Literature showed that insulin resistance was associated with the dysfunction of SIRT1, TGF-β1 protein expression and pro-apoptotic pathways. In the current research, we aimed to investigate the ameliorative effect of oxymatrine (OMT) against streptozotocin-nicotinamide (STZ-NA) induced DCM in the experimental animals. Method Male wistar rats (120–150 g) were pre-treated with the NA (110 mg/kg, i.p) followed by administration of STZ (60 mg/kg, i.p) after 15 min. After observed the onset of cardiomyopathy evaluated by increased diastolic dysfunction followed by systolic, two weeks later of STZ-NA administration, animals were divided in to various treatment groups. Diabetic animals were treated with pioglitazone (10mg/kg, p.o) and OMT(25, 100, 150 mg/kg, i.p) for 3 weeks. Various biochemical parameters were checked after completion of the experimental protocol. Key findings: Diabetic animals showed hyperglycemia, impaired glucose tolerance and lipid profile. In addition, increased blood pressure, serum LDH, CK-MB levels, and abnormal hemodynamic. Apart from this, pro-inflammatory cytokines, apoptotic markers, TGF-β1 activity were increased and SIRT1 activity was decreased in thediabetic animals. While, treatment with the OMT, restored all these abnormalities. Additionally, OMT treatment dose dependently restored the anti-oxidants, pro-inflammatory, and apoptotic marker. On the basis of these observations, we concluded that OMT can protect diabetic rats from insulin resistance through the regulation of SIRT1/Nrf2, TGF-β1 and pro-apoptotic pathways.

Publisher

Research Square Platform LLC

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