Polyphenol-enriched Desmodium elegans DC. ameliorate scopolamine-induced amnesia in animal model of Alzheimer's disease: In Vitro, In Vivo and In Silico approaches

Biomed Pharmacother. 2023 Sep:165:115144. doi: 10.1016/j.biopha.2023.115144. Epub 2023 Jul 11.

Abstract

The current study aims to quantify HPLC-DAD polyphenolics in the crude extracts of Desmodium elegans, evaluating its cholinesterase inhibitory, antioxidant, molecular docking and protective effects against scopolamine-induced amnesia in mice. A total of 16 compounds were identified which include gallic acid (239 mg g-1), p-hydroxybenzoic acid (11.2 mg g-1), coumaric acid (10.0 mg g-1), chlorogenic acid (10.88 mg g-1), caffeic acid (13.9 mg g-1), p-coumaroylhexose (41.2 mg g-1), 3-O-caffeoylquinic acid (22.4 mg g-1), 4-O-caffeoylquinic acid (6.16 mg g-1), (+)-catechin (71.34 mg g-1), (-)-catechin (211.79 mg g-1), quercetin-3-O-glucuronide (17.9 mg g-1), kaempferol-7-O-glucuronide (13.2 mg g-1), kaempferol-7-O-rutinoside (53.67 mg g-1), quercetin-3-rutinoside (12.4 mg g-1), isorhamnetin-7-O-glucuronide (17.6 mg g-1) and isorhamnetin-3-O-rutinoside (15.0 mg g-1). In a DPPH free radical scavenging assay, the chloroform fraction showed the highest antioxidant activity, with an IC50 value of 31.43 µg mL-1. In an AChE inhibitory assay, the methanolic and chloroform fractions showed high inhibitory activities causing 89% and 86.5% inhibitions with IC50 values of 62.34 and 47.32 µg mL-1 respectively. In a BChE inhibition assay, the chloroform fraction exhibited 84.36% inhibition with IC50 values of 45.98 µg mL-1. Furthermore, molecular docking studies revealed that quercetin-3-rutinoside and quercetin-3-O-glucuronide fit perfectly in the active sites of AChE and BChE respectively. Overall, the polyphenols identified exhibited good efficacy, which is likely as a result of the compounds' electron-donating hydroxyl groups (-OH) and electron cloud density. The administration of methanolic extract improved cognitive performance and demonstrated anxiolytic behavior among tested animals.

Keywords: Alzheimer’s disease; Amnesia; Desmodium elegans DC.; Molecular docking; Oxidative stress; Polyphenolics.

MeSH terms

  • Alzheimer Disease* / chemically induced
  • Alzheimer Disease* / drug therapy
  • Amnesia / chemically induced
  • Amnesia / drug therapy
  • Animals
  • Antioxidants / adverse effects
  • Chloroform / adverse effects
  • Cholinesterase Inhibitors / adverse effects
  • Glucuronides
  • Kaempferols / pharmacology
  • Kaempferols / therapeutic use
  • Methanol / chemistry
  • Mice
  • Models, Animal
  • Molecular Docking Simulation
  • Plant Extracts / adverse effects
  • Polyphenols / adverse effects
  • Quercetin / adverse effects
  • Rutin
  • Scopolamine*

Substances

  • Scopolamine
  • Kaempferols
  • Polyphenols
  • Chloroform
  • Quercetin
  • caffeoylquinic acid
  • Glucuronides
  • Plant Extracts
  • Cholinesterase Inhibitors
  • Antioxidants
  • Methanol
  • Rutin