The Potential of <i>Hibiscus sabdariffa</i> Linn in Inducing Glucagon-Like Peptide-1 via SGLT-1 and GLPR in DM Rats

Abstract

Background . Glucagon-like peptide 1 (GLP-1) hormone is an incretin hormone that is secreted in the ileum and plays a role in the pancreas to increase insulin secretion, stimulate proliferation, and prevent pancreatic β -cell apoptosis. Currently, diabetes mellitus (DM) treatment based on GLP-1 work is being developed, for instance, from herbal plants such as Hibiscus sabdariffa Linn ( H. sabdariffa ). Therefore, this study aims to determine the potential of H. sabdariffa in GLP-1 secretion in the ileum and its action in pancreatic β -cells. In addition, this study also aims to determine the active ingredients of H. sabdariffa (Hib) that interact with sodium-glucose cotransporter-1 (SGLT-1) so that it can increase GLP-1 secretion in the ileum and interact with GLP-1 receptors (GLP-1R) in the pancreas. Method . This experimental study used 24 experimental animals of Sprague–Dawley type (aged 8–10 weeks, weight 200–250 g) that were divided into 6 groups, namely, (i) normal (C), (ii) normal-Hib 200 (C-Hib200), (iii) normal-Hib 500 (C-Hib500), (iv) DM (C-DM), (v) DM-Hib200, and (vi) DM-Hib500. H. sabdariffa extract was given orally once a day for 5 weeks. Testing of GLP-1 levels in the ileum and pancreatic tissue was performed by enzyme-linked immunosorbent assay. The prediction of the interaction mechanism of the active substance H. sabdariffa against GLP-1 was done using molecular docking. Results . There was a decrease in GLP-1 levels in the ileum of DM rats (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M1"><mml:mrow><mml:mi>p</mml:mi><mml:mo>&lt;</mml:mo><mml:mn>0.05</mml:mn></mml:mrow></mml:math>). However, DM rats administered H. sabdariffa 500 mg/kg BW had GLP-1 levels that were the same as in normal rats (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M2"><mml:mrow><mml:mi>p</mml:mi><mml:mo>&gt;</mml:mo><mml:mn>0.05</mml:mn></mml:mrow></mml:math>). This is due to active ingredients such as leucosin, which binds to SGLT-1. Administration of 500 mg/kg BW H. sabdariffa in DM rats resulted in GLP-1 levels in the pancreas that were the same as in normal rats (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M3"><mml:mrow><mml:mi>p</mml:mi><mml:mo>&gt;</mml:mo><mml:mn>0.05</mml:mn></mml:mrow></mml:math>). In addition, the active ingredient of H. sabdariffa , delphinidin, binds to GLPR in the pancreas. Conclusion . The active ingredient of H. sabdariffa can increase GLP-1 secretion in the ileum and can interact with G protein-linked receptors in the pancreas.