To the best of our knowledge, DHE's effect on HF has not been clarified. Dehydrocostus lactone (DHE) is the active constituent of Saussurea lappa and is widely used in traditional Chinese medicine for its multiple biological functions, including anti-inflammatory, antioxidant and anti-cancer. Heart failure (HF) is the leading cause of death around the world, the mortality caused by HF is growing rapidly, and has become a great threaten to both public health and economic growth. Elucidation of the molecular mechanisms of α-arrestin proteins would provide a new pharmacological basis for developing approaches against cancer and type 2 diabetes mellitus. The α-arrestin family possesses PPXY motifs and may function as an adaptor/scaffold for NEDD family ubiquitin ligases. Thioredoxin binding protein -2-like inducible membrane protein/ arrestin domain containing 3 regulates endocytosis of receptors such as the β(2)-adrenergic receptor. Thioredoxin binding protein -2 regulates transcription of metabolic regulating genes.
These changes are important characteristics of type 2 diabetes mellitus.
Enhancement of thioredoxin binding protein -2 expression causes impairment of insulin sensitivity and glucose-induced insulin secretion, and β-cell apoptosis. Studies have also revealed roles for thioredoxin binding protein -2 in metabolic control. Mice with mutations or knockout of the thioredoxin binding protein -2 gene are much more susceptible to carcinogenesis than wild-type mice, indicating a role for thioredoxin binding protein -2 in cancer suppression. Thioredoxin binding protein -2 expression is downregulated in tumor cells and the level of thioredoxin binding protein is correlated with clinical stage of cancer. Thioredoxin binding protein -2/ thioredoxin interacting protein is an α-arrestin protein that has attracted much attention as a multifunctional regulator.
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