844-P: Jatupalathika Extract Acts via G-Protein-Coupled Receptors to Stimulate GLP-1 Secretion in STC-1 Cell Line

Abstract

One of the most important molecular targets for the prevention and treatment of diabetes is glucagon-like peptide-1 (GLP-1) , a molecule secreted by enteroendocrine L cells in the intestine. It has been reported that nutrients, as well as non-nutritional dietary factors, can activate GLP-1 secretion. Jatupalathika (JPT) is a traditional herbal formulation of four dried fruits: Terminalia bellirica (Gaertn.) Roxb., Terminalia chebula Retz., Terminalia arjuna (Roxb.) Wight & Arn., and Phyllanthus emblica Linn. JPT extracts have traditionally been used for their anti-oxidant, anti-aging, body fat depletion, and weight loss properties. However, its effects on glucose metabolism and GLP-1 are not known. Thus, we evaluated the antidiabetes potential of JPT aqueous extracts by assessing its ability to induce GLP-1 secretion in a mouse intestinal cell line (STC-1) . The MTT assay was used to assess the cytotoxicity, and the LUMINEX multiplex assays were used to assess GLP-1 hormone secretion. When compared to control, JPT extracts (125 µg/ml) increased GLP-1 secretion after 45-120 minutes of incubation without any effects on cell survival. The mechanism of action of GLP-1 secretion activity in cells was studied using real-time PCR. We discovered an increase in expression of six genes related to GLP-1 secretion: SLC5A1 (encoding SGLT1) , FFAR2 (encoding GPR43) , FFAR3 (encoding GPR41) , GPR119, GPBAR1, and CABP1. This finding demonstrated that JTP extract significantly increased GLP-1 hormone production via G-protein-coupled receptor activation, which also promotes Ca2+ release from the endoplasmic reticulum. Phytochemical profiling and molecular docking study revealed that Ellagic acid and Orientin are abundant metabolites with a favorable ability to bind the FFAR2/3 protein, acting as potential agents that aid in GLP-1 production. The findings showed that JPT might be useful in the prevention and treatment of diabetes. However, more research on in vivo effects is required. Disclosure C.Chaichana: None. N.Khumkhana: None. P.Wongshaya: None. W.Deekum: None. P.Pramyothin: Research Support; Novo Nordisk, Speaker's Bureau; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk.