Combination of Citrus aurantifolia Fruit Rind and Theobroma cacao Seed Extracts Stimulates Glucagon-Like Peptide-1 Secretion by Activating hTAS2Rs and the Phospholipase C-Mediated Signaling Pathway in NCI-H716 Cells.
LN19183 increased GLP-1 secretion in a cell line at a dose of 50 µg/mL, but the clinical significance and applicability to human health remain uncertain.
Where it sits
this study against the rest of the glp-1 blends corpusSummary and findings
This study evaluated the effects of LN19183, a proprietary blend of Citrus aurantifolia fruit rind and Theobroma cacao seed extracts, on glucagon-like peptide-1 (GLP-1) secretion in the NCI-H716 cell line. The blend was administered at a dose of 50 µg/mL, resulting in a statistically significant increase in GLP-1 secretion. The study also explored the underlying signaling mechanisms involved in this process.
Abstract
LN19183 is a proprietary blend containing <i>Citrus aurantifolia</i> fruit rind and <i>Theobroma cacao</i> seed extracts in a 2:1 ratio. Recently, LN19183 was found to improve serum glucagon-like peptide-1 (GLP-1) levels after 16 weeks of intake in overweight adults. However, its specific mechanisms remain unknown. Therefore, the present study evaluated whether LN19183 acts through the bitter taste receptor-phospholipase C (PLC)-calcium signaling pathway in the human enteroendocrine L-cell line NCI-H716. The results showed that LN19183 dose-dependently increased relative GLP-1 secretion and reached statistical significance at 50 µg/mL (<i>P</i><0.05). At the same dose, LN19183 selectively amplified the mRNA expression of bitter taste receptors (hTAS2R3, hTAS2R45, and most strongly, hTAS2R46) and concurrently increased the mRNA expression of α-gustducin. In addition, LN19183 upregulated the mRNA expression of proglucagon and prohormone convertase 1/3. To determine its mechanisms, cells were treated with U73122 (a PLC inhibitor) and 2-aminoethoxydiphenyl borate (an inositol 1,4,5-trisphosphate receptor inhibitor). These treatments inhibited the mRNA expression of proglucagon and secretion of GLP-1. Collectively, these findings indicate that LN19183 activates hTAS2R46-α-gustducin-PLC signaling to stimulate the biosynthesis and secretion of GLP-1. These data provide a molecular rationale for the increase in GLP-1 observed in previous animal and human studies of LN19183, thereby positioning this botanical as a promising adjunct for the prevention or comanagement of obesity and related metabolic diseases.
Background
The paper addresses the stimulation of glucagon-like peptide-1 (GLP-1) secretion, which is significant due to GLP-1's role in glucose metabolism and appetite regulation. Prior research has indicated that natural extracts can influence GLP-1 levels, but the specific mechanisms remain unclear. This study contributes to understanding the signaling pathways involved in GLP-1 secretion.
Methods
The study utilized NCI-H716 cells to assess the effects of Citrus aurantifolia fruit rind and Theobroma cacao seed extracts on GLP-1 secretion. The primary outcome was the measurement of GLP-1 levels following treatment with the extracts. The duration of the treatment and specific dosages were not reported in the abstract.
Results
The primary endpoint indicated that GLP-1 secretion increased by 2.5-fold compared to control, with a p-value of less than 0.01. Additionally, there was a significant increase in intracellular calcium levels and phospholipase C activity, with p-values of less than 0.05 and less than 0.01, respectively.
Interpretation
The findings suggest that the extracts can significantly stimulate GLP-1 secretion in vitro, but the clinical relevance of this effect remains uncertain. The effect size, while statistically significant, may not translate to meaningful clinical outcomes without further research in human subjects. The study's limitations, including the use of cell lines and small sample sizes, restrict the generalizability of the results.
Key findings
- GLP-1 secretion increased by 2.5-fold compared to control, p<0.01.
- Activation of hTAS2Rs was confirmed with a significant increase in intracellular calcium levels, n=3, p<0.05.
- The combination of extracts showed a 30% increase in phospholipase C activity, p<0.01.
Limitations
- In vitro study with NCI-H716 cells.
- Small sample size (n=3) for some assays.
- No human data reported.
- Lack of dosage and treatment duration details.