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.

Advanced Bioinformatics Tools in the Pharmacokinetic Profiles of Natural and Synthetic Compounds with Anti-Diabetic Activity

“…The inhibition of pancreatic enzymes α-amylase and α-glucosidases may be a mechanism by which the compounds in this plant manifest their antidiabetic capacity. The compounds isolated from L. axillare are p-sitosterol-3-palmitate, p-sitosterol, myricetin and gallic acids [ 82 ].…”

“…According to the observations of Abdel-Sattar et al, the root extract of Limonium axillare exhibits anti-diabetic properties such as raising insulin secretion, increasing GLUT2 and GLUT4 expression, and thereby increasing glucose absorption. The root extract’s main ingredients may have a binding affinity for GPDH, according to molecular docking analyses ( Table 1 ) [ 82 ].…”

Non‐polar metabolites of green beans ( Phaseolus vulgaris L.) potentiate the antidiabetic activity of mesenchymal stem cells in streptozotocin‐induced diabetes in rats

“…However the high cost and potential side effects limit the use of these therapeutics by many people in developing countries. For hundred years, scientists were interested in exploring blood glucose-lowering agents from plants especially those with documented ethnobotanical use (Abdel-Sattar et al, 2021;Hago et al, 2021). Thus, investigating bioactive plant secondary metabolites is an essential part of the drug discovery efforts for DM.…”