Daidzin enhances memory and the antischizophrenia drug olanzapine's effects, possibly through the 5‐HT_2A and D₂ receptor interaction pathways

Schizophrenia affects identification and disturbs our thinking and motivational capacity. Long-term use of daidzin (DZN) is evident to enhance attention and memory in experimental animals. This study aimed to investigate the effect of DZN on Swiss mice. To check animals' attention, identification, thinking, and motivational ability, we performed behavioral studies using marble burying, dust removal, and trained swimming protocols. For this, a total of 36 male Swiss albino mice were randomly divided into six groups, consisting of 6 animals in each group, as follows: control (vehicle), DZN-1.25, DZN-2.5, DZN-5 mg/kg, olanzapine (OLN)-2, and a combination of DZN-1.25 with OLN-2. Additionally, in silico studies are also performed to understand the possible molecular mechanisms behind this neurological effect. Findings suggest that DZN dose-dependently and significantly (p < .05) increased marble burying and removed dust while reducing the time to reach the target point. DZN-1.25 was found to enhance OLN's effect significantly (p < .05), possibly via agonizing its activity in animals. In silico findings suggest that DZN has strong binding affinities of -10.1 and -10.4 kcal/mol against human serotonin 2 A (5-HT_2A) and dopamine 2 (D₂) receptors, respectively. Additionally, DZN exhibits favorable pharmacokinetic and toxicity properties. We suppose that DZN may exert its attention- and memory-enhancing abilities by interacting with 5-HT_2A and D₂ receptors. It may exert a synergistic antischizophrenia-like effect with the standard drug, OLN. Further studies are required to discover the exact molecular mechanism for this neurological function in animals.