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

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Ansari, Prawej and Azam, Shofiul and Seidel, Veronique and Abdel-Wahab, Yasser H A (2022) In vitro and in vivo antihyperglycemic activity of the ethanol extract of Heritiera fomes bark and characterization of pharmacologically active phytomolecules. Journal of Pharmacy and Pharmacology, 74 (3). pp. 415-425. ISSN 0022-3573 (https://doi.org/10.1093/jpp/rgac010)

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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.

ORCID iDs

Ansari, Prawej, Azam, Shofiul, Seidel, Veronique ORCID logoORCID: https://orcid.org/0000-0003-3880-5261 and Abdel-Wahab, Yasser H A;
CORE (COnnecting REpositories)