Aspalathin and Nothofagin from Rooibos ( Aspalathus linearis ) Inhibits High Glucose-Induced Inflammation In Vitro and I
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Aspalathin and Nothofagin from Rooibos (Aspalathus linearis) Inhibits High Glucose-Induced Inflammation In Vitro and In Vivo Sae-Kwang Ku,1 Soyoung Kwak,2 Yaesol Kim,2 and Jong-Sup Bae2,3
Abstract—Vascular inflammation plays a key role in the initiation and progression of atherosclerosis, a major complication of diabetes mellitus. Aspalathin (Asp) and nothofagin (Not) are two major active dihydrochalcones found in green rooibos, which have been reported for their antioxidant activity. In this study, we assessed whether Asp or Not can suppress vascular inflammation induced by high glucose (HG) in human umbilical vein endothelial cells (HUVECs) and mice. We monitored the effects of Asp or Not on HG-induced vascular hyperpermeability, expression of cell adhesion molecules (CAMs), formation of reactive oxygen species (ROS), and activation of nuclear factor (NF)-κB in vitro and in vivo. Our data indicate that HG markedly increased vascular permeability, monocyte adhesion, expression of CAMs, formation of ROS, and activation of NF-κB. Remarkably, treatment of Asp or Not inhibited HG-mediated vascular hyperpermeability, adhesion of monocytes toward HUVECs, and expression of CAMs. In addition, Asp or Not suppressed the formation of ROS and the activation of NFκB. Since vascular inflammation induced by HG is critical in the development of diabetic complications, our results suggest that Asp or Not may have significant benefits in the treatment of diabetic complications. KEY WORDS: aspalathin; nothofagin; high glucose; diabetes mellitus; inflammation.
INTRODUCTION
a major public health issue that is rapidly getting worse, in part, due to its impact on adults of working age in developing countries [3]. Approximately 366 million people have diabetes, among which, 80 % resides in developing countries. Further, this number is expected to rise to 552 million by 2030 [1]. Although diabetes is generally not recorded as a cause of death, complications from diabetes are believed to be the fifth leading cause of death after communicable diseases, cardiovascular disease, cancer, and injuries [4]. Diabetes can be managed by regular exercise, diet, oral medication, or insulin. However, the available therapeutics are limited in their ability to treat diabetes mellitus due to a lack of systemic efficacy, issues with patient compliance, and adverse side effects [5]. As such, there has been a widespread effort to identify alternative therapies, such as effective hypoglycemic agents, for the treatment of diabetes mellitus. Recently, the World Health Organization (WHO) recommended evaluation of plants for the treatment of diseases that lack safe and effective therapeutics [6]. Management of diabetes without any side
Diabetes mellitus is a metabolic disorder affecting carbohydrate, fat, and protein metabolism, and it represents a heterogeneous group of disorders having hyperglycemia, which is due to impaired glucose utilization resulting from a defective or deficient insulin secretory response [1, 2]. Along with hyperglycemia and abnormalit
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