Pinoresinol-4-O-β-D-glucopyranoside: a lignan from prunes (Prunus domestica) attenuates oxidative stress, hyperglycaemia and hepatic toxicity in vitro and in vivo

J Pharm Pharmacol. 2020 Dec;72(12):1830-1839. doi: 10.1111/jphp.13358. Epub 2020 Aug 27.

Abstract

Objectives: This study aimed to explore the pharmacological properties of pinoresinol-4-O-β-D-glucopyranoside (PG), isolated from prunes.

Methods: In-vitro antioxidant activity was assessed using ferric reducing antioxidant power (FRAP) and 2,2'-azino-bis [3-ethylbenzothiazoline-6-sulfonic acid]-diammonium salt (ABTS) assays. In-vivo hepatoprotective activity was evaluated using CCl4 -induced hepatotoxicity mouse model. The antihyperglycaemic activity was determined in vitro using α-glucosidase and α-amylase inhibiting activity and in vivo using streptozotocin-treated model. Molecular modelling was done on α-amylase, α-glucosidase, aldose reductase and peroxisome proliferator-activated receptor gamma.

Key findings: Pinoresinol-4-O-β-D-glucopyranoside showed promising antioxidant activity in FRAP and ABTS assays with total antioxidant capacity equal 418.47 and 1091.3 µmol/g in terms of ascorbic acid, respectively. PG (50 mg/kg b.w.) exhibited a hepatoprotective activity in vivo as it lowered AST and ALT levels. PG showed a potent in-vitro antihyperglycaemic activity as it inhibited α-glucosidase with an IC50 value of 48.13 μg/ml. PG caused a prominent decline in serum glucose level by 37.83% in streptozotocin-treated mice with promising elevation in insulin level of 25.37%. Oxidative stress markers were reduced by PG, and it showed a high fitting on α-amylase and α-glucosidase active sites.

Conclusions: Pinoresinol-4-O-β-D-glucopyranoside is a natural entity combating oxidative stress, hepatic damage and diabetes.

Keywords: Prunus domestica; antihyperglycaemic activity; hepatoprotective; molecular modelling; pinoresinol-4-O-β-D-glucopyranoside; streptozotocin.

MeSH terms

  • Animals
  • Antioxidants / isolation & purification
  • Antioxidants / pharmacology*
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Carbon Tetrachloride
  • Chemical and Drug Induced Liver Injury / etiology
  • Chemical and Drug Induced Liver Injury / metabolism
  • Chemical and Drug Induced Liver Injury / pathology
  • Chemical and Drug Induced Liver Injury / prevention & control*
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Experimental / chemically induced
  • Diabetes Mellitus, Experimental / prevention & control*
  • Fruit
  • Glucosides / isolation & purification
  • Glucosides / pharmacology*
  • Glycoside Hydrolase Inhibitors / isolation & purification
  • Glycoside Hydrolase Inhibitors / pharmacology*
  • Insulin / blood
  • Lignans / isolation & purification
  • Lignans / pharmacology*
  • Liver / drug effects*
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Mice
  • Molecular Docking Simulation
  • Oxidative Stress / drug effects*
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Prunus domestica* / chemistry
  • Streptozocin
  • alpha-Amylases / antagonists & inhibitors
  • alpha-Amylases / metabolism
  • alpha-Glucosidases / metabolism

Substances

  • Antioxidants
  • Blood Glucose
  • Glucosides
  • Glycoside Hydrolase Inhibitors
  • Insulin
  • Lignans
  • Plant Extracts
  • pinoresinol 4-O-glucopyranoside
  • Streptozocin
  • Carbon Tetrachloride
  • alpha-Amylases
  • alpha-Glucosidases