Abstract
Phloroglucinol is a phenolic compound that is one of the major compounds in Ecklonia cava (brown alga). It has many pharmacological activities, but its anti-diabetic effect is not yet fully explored. In this study, we investigated the effect of phloroglucinol on the control of blood glucose levels and the regulation of hepatic glucose production. Phloroglucinol significantly improved glucose tolerance in male C57BL/6J mice fed a high fat diet (HFD) and inhibited glucose production in mouse primary hepatocytes. The expression of phosphoenol pyruvate carboxykinase (PEPCK) and glucose-6-phosphatase mRNA and protein (G6Pase), enzymes involved in gluconeogenesis, were inhibited in liver tissue from phloroglucinol-treated mice and in phloroglucinol-treated HepG2 cells. In addition, phloroglucinol treatment increased phosphorylated AMP-activated protein kinase (AMPK)α in HepG2 cells. Treatment with compound C, an AMPKα inhibitor, inhibited the increase of phosphorylated AMPKα and the decrease of PEPCK and G6Pase expression caused by phloroglucinol treatment. We conclude that phloroglucinol may inhibit hepatic gluconeogenesis via modulating the AMPKα signaling pathway, and thus lower blood glucose levels.
Highlights
Hepatic glucose production is a key physiological process that becomes altered in diabetic patients and represents the main target of the anti-hyperglycemic effect of biguanides [1,2]
To address whether phloroglucinol has an effect on blood glucose levels, six-week-old C57BL6 male mice were fed an high fat diet (HFD) for 10 weeks and orally administered 100 mg/kg of phloroglucinol daily for 9 weeks
In order to investigate whether phloroglucinol treatment affects phosphoenol pyruvate carboxykinase (PEPCK) and glucose-6-phosphatase mRNA and protein (G6Pase) gene expression in the liver, we performed Western blotting analysis for PEPCK and G6Pase protein expression in liver tissue of the HFD + phloroglucinol and HFD + phosphate-buffered saline (PBS)
Summary
Hepatic glucose production is a key physiological process that becomes altered in diabetic patients and represents the main target of the anti-hyperglycemic effect of biguanides [1,2]. E. cava extract reduces blood glucose levels and increases insulin levels in streptozotocin-induced diabetic mice, a model of type 1 diabetes [10], and the dieckol-rich extract of E. cava improves glucose and lipid metabolism in C57BL/KsJ-db/db mice, a model of type 2 diabetes [11]. The extract of E. cava produced from the Gijang area in Korea is more effective for weight loss and reducing hyperglycemia in high fat diet (HFD)-induced obese mice compared to the extract of E. cava from the Jeju area in Korea [12,13]. Further study showed that Gijang E. cava extract has higher concentrations of phloroglucinol than Jeju E. cava extract [12]
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