Stevioside improved hyperglycemia-induced cardiac dysfunction by attenuating the development of fibrosis and promoting the degradation of established fibrosis

Abstract

Stevioside, a non-caloric sweetener, has been used for nutritional therapy to diabetic patients; but there are few reports about the effects of stevioside on hyperglycemia-induced cardiac fibrosis. This present studies showed that stevioside improved hyperglycemia-induced cardiac dysfunction by attenuating the development of cardiac fibrosis; whose mechanism is to inhibit transforming growth factor beta (TGF-β) pathway, cardiac fibroblast transformation, and reduce collagen cross-linking through down-regulating the expressions of lysyl oxidase (LOX) and lysyl oxidase like 2 (LOXL2). Moreover, after 8 weeks of glycemic control by insulin or insulin plus stevioside, insulin plus stevioside induced the stronger degradation of cardiac fibrosis compared to only insulin treatment. This mechanism was partly due to regulate the expressions of matrix metallopeptidase (MMP) 2/9 and tissue inhibitor of metalloproteinase (TIMP) 2/4. Briefly, our research revealed that in addition to hypoglycemic, stevioside also had great potential in adjuvant treatment of cardiac fibrosis caused by hyperglycemia.

Keywords

• Type 1 diabetes
• Cardiac fibrosis
• Stevioside
• Insulin
• Collagen cross-linking
• Degradation of fibrosis