Abstract
Coptisine is the major bioactive protoberberine alkaloid found in Rhizoma Coptidis. Coptisine reduces inflammatory responses and improves glucose tolerance; nevertheless, whether coptisine has vasoprotective effect in diabetes is not fully characterized. Conduit arteries including aortas and carotid arteries were obtained from male C57BL/6J mice for ex vivo treatment with risk factors (high glucose or tunicamycin) and coptisine. Some arterial rings were obtained from diabetic mice, which were induced by high-fat diet (45% kcal% fat) feeding for 6 weeks combined with a low-dose intraperitoneal injection of streptozotocin (120 mg/kg). Functional studies showed that coptisine protected endothelium-dependent relaxation in aortas against risk factors and from diabetic mice. Coptisine increased phosphorylations of AMPK and eNOS and downregulated the endoplasmic reticulum (ER) stress markers as determined by Western blotting. Coptisine elevates NO bioavailability and decreases reactive oxygen species level. The results indicate that coptisine improves vascular function in diabetes through suppression of ER stress and oxidative stress, implying the therapeutic potential of coptisine to treat diabetic vasculopathy.
Highlights
Cardiovascular disease (CVD) is a multifactorial disease with a high mortality rate in the world, where obesity and diabetes are the major risk factors [1]
ResuMlotusse aortas were incubated with high glucose (30 mM, 48 h) to mimic the hyperglycemic condition in diabetes and we found that ex vivo high glucose exposure impaired
The present results suggest that coptisine has sufficient therapeutic value to prevent endothelial dysfunction in diabetes; this probably occurs through the inhibition of endoplasmic reticulum (ER) stress and oxidative stress, as well as the restoration of nitric oxide (NO) production in arteries, based on the following observations
Summary
Cardiovascular disease (CVD) is a multifactorial disease with a high mortality rate in the world, where obesity and diabetes are the major risk factors [1]. Studies have shown that hyperglycemia causes endothelial damage and thereby endothelial dysfunction, which is the main serious complication of diabetes [3]. The recognized complex mechanisms by which hyperglycemia modifies endothelial function include reduction in nitric oxide (NO) bioavailability [4], production of vasoconstrictors such as endothelin-1 (ET-1) [5], increased generation of reactive oxygen species (ROS) [6], and glycation of proteins and lipids [7]. Any situation in which the endothelial nitric oxide synthase (eNOS) activity is reduced or the ROS production is elevated can lead to a lowered NO bioavailability and, impair endothelium-dependent vasodilatations. The phosphorylation of eNOS is decreased in diabetic mouse aortas and AMP-activated protein kinase (AMPK) phosphorylation is one of the major types of signalling to stimulate eNOS [8,9]
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