Diabetic cardiomyopathy: Mechanisms and new treatment strategies targeting antioxidant signaling pathways

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality among patients with diabetes mellitus (DM). DM can lead to multiple cardiovascular complications, including coronary artery disease (CAD), cardiac hypertrophy, and heart failure (HF). HF represents one of the most common causes of death in patients with DM and results from DM-induced CAD and diabetic cardiomyopathy. Oxidative stress is closely associated with the pathogenesis of DM and results from overproduction of reactive oxygen species (ROS). ROS overproduction is associated with hyperglycemia and metabolic disorders, such as impaired antioxidant function in conjunction with impaired antioxidant activity. Long-term exposure to oxidative stress in DM induces chronic inflammation and fibrosis in a range of tissues, leading to formation and progression of disease states in these tissues. Indeed, markers for oxidative stress are overexpressed in patients with DM, suggesting that increased ROS may be primarily responsible for the development of diabetic complications. Therefore, an understanding of the pathophysiological mechanisms mediated by oxidative stress is crucial to the prevention and treatment of diabetes-induced CVD. The current review focuses on the relationship between diabetes-induced CVD and oxidative stress, while highlighting the latest insights into this relationship from findings on diabetic heart and vascular disease.

/pdf/diabetic-cardiovascular-disease-induced-by-oxidative-stress-46z5qwsl5g.pdf

Diabetic Cardiovascular Disease Induced by Oxidative Stress

Objectives
Even with great advances in modern medicine and therapeutic agent development, the search for effective antidiabetic drugs remains challenging. Coumarins are secondary metabolites found widely in nature plants and used mainly in anticoagulation and antithrombotic therapy. Over the past two decades, however, there has been an increasing body of literatures related to the effects of coumarins and their derivatives on diabetes and its complications. This review aimed to focus on research findings concerning the effects of coumarins against diabetes and its complications using in-vitro and in-vivo animal models, and also to discuss cellular and molecular mechanisms underlying these effects.

Key findings
The search for new coumarins against diabetes and it complications, either isolated from traditional medicine or chemically synthesized, has been constantly expanding. The cellular and molecular mechanisms involved include protecting pancreatic beta cells from damage, improving abnormal insulin signalling, reducing oxidative stress/inflammation, activating AMP-activated protein kinase (AMPK), inhibiting α-glucosidases and ameliorating diabetic complications.

Conclusions
The effects and mechanisms of coumarins and their derivatives upon diabetes and its complications are discussed in current review. Further investigations remain to be carried out to develop a promising antidiabetic agent based on coumarin cores.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/jphp.12774

Coumarins as potential antidiabetic agents.

Plants are widely used in many indigenous systems of medicine for therapeutic purposes and are increasingly becoming popular in modern society as alternatives to synthetic medicines. Bioactive principles are derived from the products of plant primary metabolites, which are associated with the process of photosynthesis. The present review highlighted the chemical diversity and medicinal potentials of bioactive principles as well inherent toxicity concerns associated with the use of these plant products, which are of relevance to the clinician, pharmacist or toxicologist. Plant materials are composed of vast array of bioactive principles of which their isolation, identification and characterization for analytical evaluation requires expertise with cutting edge analytical protocols and instrumentations. Bioactive principles are responsible for the therapeutic activities of medicinal plants and provide unlimited opportunities for new drug leads because of their unmatched availability and chemical diversity. For the most part, the beneficial or toxic outcomes of standardized plant extracts depend on the chemical peculiarities of the containing bioactive principles.

Dhamodaran Prabakaran

Papers

Protective effect of esculetin on hyperglycemia-mediated oxidative damage in the hepatic and renal tissues of experimental diabetic rats.

Antihyperglycemic effect of esculetin modulated carbohydrate metabolic enzymes activities in streptozotocin induced diabetic rats