Abstract:
The current study utilizes in silico molecular docking/molecular dynamics
to evaluate the binding affinity of apigenin and safranal with 5HT1AR/5HT2AR, followed by
assessment of in vivo effects of these compounds on depressive and anxious behavior. Methods:
The docking between apigenin and safranal and the 5HT1A and 5HT2A receptors was performed
utilizing AutoDock Vina software, while MD and protein-lipid molecular dynamics simulations were
executed by AMBER16 software. For in vivo analysis, healthy control (HC), disease control (DC),
fluoxetine-, and apigenin-safranal-treated rats were tested for changes in depression and anxiety
using the forced swim test (FST) and the elevated plus-maze test (EPMT), respectively. Results: The
binding affinity estimations identified the superior interacting capacity of apigenin over safranal for
5HT1A/5HT2A receptors over 200 ns MD simulations. Both compounds exhibit oral bioavailability
and absorbance. In the rodent model, there was a significant increase in the overall mobility time in
the FST, while in the EPMT, there was a decrease in latency and an increase in the number of entries
for the treated and HC rats compared with the DC rats, suggesting a reduction in depressive/anxiety
symptoms after treatment. Conclusions: Our analyses suggest apigenin and safranal as prospective
medication options to treat depression and anxiety.