Hexacosylidenecyclohexane inhibits enzymatic breakdown of dietary sugars and modulates glucose homeostasis

Abstract

Background: The quest for benign drug to treat diabetes and its complications is a major scientific search. The investigation evaluates the antidiabetic properties of hexacosylidenecyclohexane purified from Madhuca longifolia by advanced chromatographic approach. Methods: Chloroform, methanol and hexane fractions were analysed by TLC and HPLC to isolate the active molecule followed with structure elucidation by LC-MS, FTIR, CHN and NMR spectroscopy. In vitro and in vivo antidiabetic methods were adopted to ascertain the potency of the active molecule. Drug-likeness and ADMET analysis of the molecule were carried out using Molinspiration, SwissADME, DruLiTo software, ADMETlab and admetSAR prediction tools. Results: Bioassay guided fractionation and purification of the crude extract resulted in 25 fractions; MBCF1 to MBCF25 (M. longifolia bark chloroform fraction). MBCF2 showed effective in vitro inhibition of aldose reductase, α-amylase and α-glucosidase with an IC50 value of 85, 30 and 21 µg/mL, respectively. The active molecule, hexacosylidenecyclohexane at a dose of 50 mg /kg b.w., reduced the blood glucose level to 239 from 340 mg /dL on day 14 (experimental period) and at 25 mg /kg b.w., from 348 to 277 mg /dL. It showed significant reversal of lipid profile and bile acids. Histopathological studies revealed the protective effect on cellular population and size of islets. Drug-likeness property was in the acceptable range with no toxic effect as predicted by ADMET analysis. Conclusion: The findings showed that, the active molecule hexacosylidenecyclohexane possesses potential antidiabetic effect with no toxic effect.

Keywords

• Antidiabetic
• Streptozotocin
• Enzymes
• Toxicity
• Drug-likeness