Spergularia marina Induces Glucagon-Like Peptide-1 Secretion in NCI-H716 Cells Through Bile Acid Receptor Activation

Abstract

Spergularia marina Griseb. (SM) is a halophyte that grows in mud flats. The aerial portions of SM have been eaten as vegetables and traditionally used to prevent chronic diseases in Korea. However, there has been no scientific report that demonstrates the pharmacological effects of SM. Glucagon-like peptide-1 (GLP-1) is important for the maintenance of glucose and energy homeostasis through acting as a signal in peripheral and neural systems. To discover a functional food for regulating glucose and energy homeostasis, we evaluated the effect of an aqueous ethanolic extract (AEE) of SM on GLP-1 release from enteroendocrine NCI-H716 cells. In addition, we explored the Takeda G-protein-coupled receptor 5 (TGR5) agonist activity of AEE-SM in Chinese hamster ovary (CHO)-K1 cells transiently transfected with human TGR5. As a result, treatment of NCI-H716 cells with AEE-SM increased GLP-1 secretion and intracellular Ca 2 + and cyclic AMP (cAMP) levels in a dose-dependent manner. Transfection of NCI-H716 cells with TGR5-specific small interference RNA inhibited AEE-SMinduced GLP-1 secretion and the increase in Ca 2 + and cAMP levels. Moreover, AEE-SM showed that the TGR5 agonist activity in CHO-K1 cells transiently transfected with TGR5. The results suggest that AEE-SM might be a candidate for a functional food to regulate glucose and energy homeostasis.

Modulation of Diabetes by Natural Products and Medicinal Plants via Incretins

“…Transfection of cells with ▶ Table 2 Medicinal plants and natural products as inhibitors of DPP-4. TGR5-specific small interference RNA inhibited all these effects, which demonstrated that S. marina-stimulated GLP-1 secretion involved TGR5 activation and is a possible candidate for antidiabetic purposes [87]. The roots of Gentiana scabra Bunge (Gentianaceae) are used in traditional Korean medicine for treatment of T2D, and its properties were associated with the intestinal bitter taste sensation, which stimulates GLP-1 secretion.…”

Effect of six Korean plants on glucagon like peptide-1 release

“…Cell culture and GLP-1 secretion studies NCI-H716 cells (the American Type Culture Collection, Manassas, VA, USA) were cultured and differentiated as reported (Reimer et al, 2001). GLP-1 secretion from the cells was measured using the method previously described (Kim et al, 2014). In brief, the cells were plated at 5 9 10 4 cells per well in 96-well microplates coated with Matrigel EC50 was calculated when the response to 250 mM glucose was considered to be the maximum and incubated for 48 h. The cells were incubated with the extracts in Krebs-Ringer bicarbonate buffer (128.8 mM NaCl, 4.8 mM KCl, 1.2 mM KH 2 PO 4 , 1.2 mM MgSO 4 , 2.5 mM CaCl 2 , 5 mM NaHCO 3 , 10 mM HEPES, and 0.2% bovine serum albumin, pH 7.4) for 1 h. GLP-1 in the supernatants were measured by a GLP-1 active ELISA kit (Millipore, Billerica, MA, USA) and expressed as folds of the untreated control.…”

“…Measurement of Ca 21 response in NCI-H716 cells Ca 2? response in the cells was measured as described previously (Kim et al, 2014). The cells (5 9 10 4 cells per well) were differentiated in Matrigel coated 96-well clearbottom plates for 48 h at 37°C.…”

“…GLP-1 is secreted when stimulated by nutrients such as glucose, amino acids, and fatty acids. Meanwhile, recent studies have showed that non-nutrient edible plant extracts such as green tea extract (Liu et al, 2014), sweet potato leaf extract (Nagamine et al, 2014), and Spergularia marina extract (Kim et al, 2014) stimulated GLP-1 secretion. By means of established model such as the human cell line NCI-H716, derived from a caecal adenocarcinoma (Parker et al, 2009), the GLP-1-secreting function of various components can be assessed.…”

A phenyl lipid alkaloid and flavone C-diglucosides from Spergularia marina

“…Spergularia marina Griseb, which is called 'sebalnamul' in Korean, is an annual halophyte (11) and a popular winter seasoned vegetable in Korea. Several studies have reported that S. marina has biological effects, such as reducing insulin resistance, and antioxidant, antiinflammation, antimicrobial, and anti-adipogenic activities (12)(13)(14)(15)(16). S. marina contains amino acids, vitamins, and minerals (11).…”