Memory-Enhancing Effects of Dauricine in Swiss Mice: Possible Molecular Interventions Through In Vivo and In Silico Studies

Neuromolecular Med. 2025 Jun 5;27(1):45. doi: 10.1007/s12017-025-08839-z.

Abstract

The bisbenzylisoquinoline alkaloid dauricine (DAU) is known for its neuroprotective effects in animals. This study investigates the memory-enhancing effects of DAU in Swiss albino mice using both in vivo and in silico approaches, focusing on its interaction with the D2 dopamine (DOP) receptor. Behavioral tests, including marble burying, dust removal, and trained swimming, were used to assess cognitive performance, anxiety, and motor coordination. Molecular docking studies revealed that DAU binds strongly to the D2 DOP receptor (6CM4 protein), with a binding affinity of - 7.9 kcal/mol, forming significant hydrogen and hydrophobic bonds. Additionally, the pharmacokinetics and toxicity profiles of DAU were also evaluated. In vivo results showed that DAU improved behavioral performance in a dose-dependent manner, with the DAU-10 group showing significant (p < 0.05) enhancement compared to the control and standard groups. The DAU-10 + DOP-22 combination group also showed remarkable results compared to the standard alone. Pharmacokinetics and toxicity profiles were also assessed, revealing favorable properties but some concerns regarding mutagenicity and immunotoxicity. These findings suggest that DAU, especially when combined with D2 DOP receptor agonists, holds significant potential for memory enhancement and warrants further investigation.

Keywords: Combination therapy; Dauricine; Dopamine receptor; Memory-enhancing effect.

MeSH terms

  • Animals
  • Anxiety
  • Behavior, Animal / drug effects
  • Benzylisoquinolines* / chemistry
  • Benzylisoquinolines* / pharmacokinetics
  • Benzylisoquinolines* / pharmacology
  • Benzylisoquinolines* / therapeutic use
  • Benzylisoquinolines* / toxicity
  • Cognition / drug effects
  • Dopamine Agonists / pharmacology
  • Dose-Response Relationship, Drug
  • Male
  • Maze Learning / drug effects
  • Memory* / drug effects
  • Mice
  • Molecular Docking Simulation
  • Motor Activity / drug effects
  • Neuroprotective Agents* / pharmacokinetics
  • Neuroprotective Agents* / pharmacology
  • Neuroprotective Agents* / toxicity
  • Nootropic Agents* / pharmacokinetics
  • Nootropic Agents* / pharmacology
  • Nootropic Agents* / toxicity
  • Protein Binding
  • Receptors, Dopamine D2* / agonists
  • Receptors, Dopamine D2* / chemistry
  • Receptors, Dopamine D2* / metabolism
  • Swimming
  • Tetrahydroisoquinolines* / pharmacokinetics
  • Tetrahydroisoquinolines* / pharmacology
  • Tetrahydroisoquinolines* / toxicity

Substances

  • Receptors, Dopamine D2
  • dauricine
  • Benzylisoquinolines
  • Tetrahydroisoquinolines
  • Neuroprotective Agents
  • Nootropic Agents
  • Dopamine Agonists