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Abstract
BackgroundRhodiola rosea (Rhodiola) is a plant in the Crassulaceae family that grows in cold regions of the world. It is mainly used in clinics as an adaptogen. Recently, it has been mentioned that Rhodiola increases plasma β-endorphin to lower blood pressure. Thus, the present study aims to investigate the antidiabetic action of Rhodiola in relation to opioids in streptozotocin-induced diabetic rats (STZ-diabetic rats).MethodsIn the present study, the plasma glucose was analyzed with glucose oxidase method, and the determination of plasma β-endorphin was carried out using a commercially available enzyme-linked immunosorbent assay. The adrenalectomy of STZ-diabetic rats was used to evaluate the role of β-endorphin. In addition, quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blotting analysis were performed to investigate mRNA and protein expressions.ResultsRhodiola-water extract dose-dependently lowered the plasma glucose in STZ-diabetic rats and this action was reversed by blockade of opioid μ-receptors using cyprodime. An increase of plasma β-endorphin by rhodiola-water extract was also observed in same manner. The plasma glucose lowering action of rhodiola-water extract was attenuated in bilateral adrenalectomized rats. In addition, continuous administration of rhodiola-water extract for 3 days in STZ-diabetic rats resulted in an increased expression of glucose transporter subtype 4 (GLUT 4) in skeletal muscle and a marked reduction of phosphoenolpyruvate carboxykinase (PEPCK) expression in liver. These effects were also reversed by blockade of opioid μ-receptors.ConclusionsTaken together, rhodiola-water extract improves hyperglycemia via an increase of β-endorphin secretion from adrenal gland to activate opioid μ-receptors in STZ-diabetic rats.
Highlights
Rhodiola rosea (Rhodiola) is a plant in the Crassulaceae family that grows in cold regions of the world
Effects of rhodiola-water extract on plasma glucose concentration and plasma β-endorphin-like immunoreactivity (BER) level in STZ-diabetic rats STZ-diabetic rats treated with rhodiola-water extract at 50 mg/kg through intraperitoneal injection produced the plasma glucose-lowering activities as 8.3 ± 1.2% at 30 min later, 22.1 ± 0.8% at 60 min later, 18.7 ± 1.4% at 90 min later and 6.7 ± 2.1% at 120 min later (n = 8)
Many actions of endogenous β-endorphin are recognized to be mediated by the opioid μ-receptors including the regulation of glucose homeostasis [34,35], but the mediation of opioid delta-receptor located in skeletal muscle regarding to the hypoglycemic effect of BER has been demonstrated [36,37]
Summary
Rhodiola rosea (Rhodiola) is a plant in the Crassulaceae family that grows in cold regions of the world. It is mainly used in clinics as an adaptogen. Rhodiola-water extract has been reported to improve hypertension via the release of β-endorphin in animal model [15]. Some chemical agents or exogenous β-endorphin might improve hyperglycemia through an activation of opioid μ-receptors in STZ-diabetic rats lacking insulin [18,19,20]. Rhodiola-water extract is used to screen the effect on hyperglycemia in diabetic rats. The mediation of β-endorphin in this action of rhodiola-water extract is further identified
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