Anti-insulin resistance effect of constituents from Senna siamea on zebrafish model, its molecular docking, and structure-activity relationships

J Nat Med. 2021 Jun;75(3):520-531. doi: 10.1007/s11418-021-01490-5. Epub 2021 Feb 23.

Abstract

Senna siamea has been used as an antidiabetic drug since antiquity. With regard to traditional Thai medicine, the use of S. siamea was described for diabetes therapy. To understand the molecular mechanism regarding insulin resistance. Pure compounds were isolated from wood extract. We studied their biological activities on insulin-resistance using an in vivo zebrafish model. We also performed an in silico study; molecular docking, and in vitro study by taking advantage of the enzyme inhibitory activities of α-glucosidase, PTP1B, and DPP-IV. Based on the preliminary investigation that ethyl acetate and ethanol extracts have potent effects against insulin resistance on zebrafish larvae, five compounds were isolated from two fractions following: resveratrol, piceatannol, dihydropiceatannol, chrysophanol, and emodin. All of the isolated compounds had anti-insulin resistance effects on zebrafish larvae. Resveratrol, piceatannol, and dihydropiceatannol also demonstrated inhibitory effects against α-glucosidase. Chrysophanol and emodin inhibited PTP1B activity, while resveratrol showed a DPP-IV inhibition effect via the molecular docking. The results of enzyme assay were similar. In conclusions, S. siamea components demonstrated effects against insulin resistance. The chemical structure displayed identical biological activity to that of the compounds. Therefore, S. siamea wood extract and their components are potential therapeutic options in the treatment of diabetes.

Keywords: Enzyme; Insulin resistance; Molecular docking; Phytochemical; Senna siamea; Zebrafish.

MeSH terms

  • Animals
  • Anthraquinones / pharmacology
  • Diabetes Mellitus
  • Dipeptidyl Peptidase 4 / metabolism
  • Emodin / pharmacology
  • Hypoglycemic Agents / pharmacology*
  • Insulin Resistance*
  • Molecular Docking Simulation
  • Molecular Structure
  • Plant Extracts / pharmacology*
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1 / metabolism
  • Resveratrol / pharmacology
  • Senna Plant / chemistry*
  • Stilbenes / pharmacology
  • Structure-Activity Relationship
  • Thailand
  • Wood / chemistry
  • Zebrafish / metabolism
  • alpha-Glucosidases / metabolism

Substances

  • Anthraquinones
  • Hypoglycemic Agents
  • Plant Extracts
  • Stilbenes
  • 3,3',4,5'-tetrahydroxystilbene
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1
  • alpha-Glucosidases
  • Dipeptidyl Peptidase 4
  • Emodin
  • chrysophanic acid
  • Resveratrol