In vitro and in vivo antihyperglycemic activity of the ethanol extract of Heritiera fomes bark and characterization of pharmacologically active phytomolecules

Abstract

Objective This study aimed to demonstrate the mechanistic basis of Heritiera fomes, which has traditionally been used to treat diabetes. Methods Clonal pancreatic β-cells and primary islets were used to measure insulin release. 3T3-L1 cells were used to analyse insulin action, and in vitro systems were used to measure further glucose-lowering activity. In vivo assessment was performed on streptozotocin (STZ)-induced type-2 diabetic rats and reversed-phase-HPLC followed by liquid chromatography mass spectrometry (LC-MS) to detect bioactive molecules. Key findings Ethanol extract of Heritiera fomes (EEHF) significantly increased insulin release with stimulatory effects comparable to 1 µM glucagon-like peptide 1, which were somewhat reduced by diazoxide, verapamil and calcium-free conditions. Insulin release was stimulated by tolbutamide, isobutyl methylxanthine and KCl. EEHF induced membrane depolarization and increased intracellular Ca2+ levels. EEHF enhanced glucose uptake in 3T3L1 cells and decreased protein glycation. EEHF significantly inhibited postprandial hyperglycaemia following sucrose loading and inversely elevated unabsorbed sucrose concentration in the gut. It suppressed glucose absorption during in situ gut perfusion. Furthermore, EEHF improved glucose tolerance, plasma insulin and gut motility, and decreased plasma dipeptidyl peptidase IV activity. Procyanidins, epicatechin and proanthocyanidins were some of the identified bioactive constituents that may involve in β-cell actions. Conclusions This study provides some evidence to support the use of H. fomes as an antidiabetic traditional remedy.

Polyphenol-Rich Leaf of Annona squamosa Stimulates Insulin Release from BRIN-BD11 Cells and Isolated Mouse Islets, Reduces (CH2O)n Digestion and Absorption, and Improves Glucose Tolerance and GLP-1 (7-36) Levels in High-Fat-Fed Rats

“…KCl and alanine cause plasma membrane depolarisation and Ca 2+ influx. Alanine does this mostly by co-transport with Na+ and metabolism with ATP production [ 11 , 14 ].…”

“…A fluorometric imaging plate reader (FLIPR) membrane potential and [Ca 2+ ] i assay kit (Molecular Devices, Sunnyvale, CA, USA) were employed to examine the effects of EEAS on the membrane potential and [Ca 2+ ] i concentrations, respectively [ 11 ]. Positive controls included depolarising concentrations of KCl (30 mM) and alanine (10 mM) [ 14 , 26 ].…”

“…The animals were fed BaSO 4 milk by oral gavage 1 h after EEAS administration, and 15 min afterwards, the animals from both groups were sacrificed. The distance travelled by the BaSO 4 milk throughout the entire length of the small intestine (from the pylorus to the ileo–caecal junction) was measured to calculate the percentage distance [ 11 ]. The standard drug glibenclamide (5 mg/5 mL/kg) was used as positive control.…”

“…A healthy diet, weight management, and regular exercise are the first steps to lowering blood sugar levels [ 10 ]. Additionally, to increase insulin secretion and improve its function, one or more oral anti-hyperglycaemic medications, such as biguanides, sulphonylureas, thiazolidinediones, SGLT-2 inhibitors, meglitinides, α-glucosidase inhibitors, DPP-IV inhibitors, GLP-1 analogues, GIP, and GLP-1 receptor co-agonists, and/or synthetic insulin, may be used [ 11 , 12 , 13 ]. However, in addition to being expensive and unavailable to people living in remote and poor areas, these synthetic drugs are associated with a number of adverse effects, including gastrointestinal disorders, weight gain, renal problems, liver diseases, and hypoglycaemia [ 11 , 14 , 15 , 16 ].…”

Pharmacologically Active Phytomolecules Isolated from Traditional Antidiabetic Plants and Their Therapeutic Role for the Management of Diabetes Mellitus

“…Other modes of action include enhancing glucose metabolism, improving β-cell mass and function, and increasing plasma insulin, thus decreasing circulating blood glucose levels [20][21][22][23]. In addition to being used to treat diabetes, these plants have also been traditionally employed to treat other conditions such as ulcers, wounds, inflammation, infections, diarrhea, dysentery, malaria, rheumatism, hypertension, obesity, pneumonia, and kidney diseases [12,19,[24][25][26]. The main objective of this review is to explore the traditional plant-based therapies and/or their phytoconstituents available for the treatment of diabetes.…”