Chemical and biological investigations of Limonium axillare reveal mechanistic evidence for its antidiabetic activity.

Abstract

Root and bark of Limonium axillare (Forssk) Kuntze are used as antidiabetic remedies in parts of East Africa, but this activity has never been fully investigated. To validate its ethnobotanical use, we compared the chemical and pharmacological profiles of the ethanolic extracts of L. axillare root (REE) and aerial parts (AEE). Administration of REE (500 mg kg-1) reduced streptozotocin-induced hyperglycemia by 44%, restored serum insulin levels, reestablished Glut2 and Glut4 expression and ameliorated pancreatic tissue damage in diabetic rats. In vitro studies revealed a strong radical scavenging effect, α-glucosidase, and α-amylase inhibition activity of REE at IC50 at 25.2, 44.8 and 89.1μg/mL, respectively. HPLC analysis identified ten phenolic compounds in REE with umbelliferone as the major constituents at 10 ± 0.081 mg/g of extract. Additionally, six compounds were isolated from REE including, β-sitosterol-3-palmitate, β-sitosterol, myricetin and gallic acids with two new tetrahydrofuran monoterpenes; 2-isopropyl- 3,4,4, trimethyl-tetrahydrofuran (3), and 2-isopropyl-4-methyl-tetrahydrofuran-3,4 dicarboxylic acid (4), the latter was revealed by molecular docking to be a good ligand to glycerol-3-phosphate dehydrogenase a key enzyme in glycolysis.