Abstract
Depression is a serious psychiatric disorder that affects millions of individuals all over the world, thus demanding special attention from researchers in order to investigate its effective remedies. Curcumin, along with its synthetic derivatives, is recognized for its incredible pharmacological activities. In this study, methyl, methoxy and chloro-substituent synthetic curcumin analogues
C1
–
C3
were respectively tested for free radical-scavenging activity. Behavioral studies were performed using chemical-induced and swimming endurance tests as stress models, and forced swim tests (FSTs) and tail suspension tests (TSTs) as depression mice models. Biochemical examinations were performed after a scopolamine-induced stress model by decapitating the mice, and brain tissues were isolated for biochemical assessment of catalase (CAT), superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA). The curcumin analogue
C2
exhibited higher DPPH (2,2-diphenyl-1-picrylhydrazyl) and ABTS (2,2′-azinobis-3-ethylbenzothiazo-line-6-sulphonate) free radical-scavenging potential, having IC
50
values of 45.18 µg/mL and 62.31 µg/mL, respectively, in comparison with reference curcumin and tocopherol. In the chemical-induced test,
C2
(80.17%),
C3
(72.79%) and
C1
(51.85%) revealed higher antistress responses by significantly reducing the number of writhes, whereas the immobility time was significantly reduced by
C2
and
C3
in the swimming endurance test, indicating excellent antistress potential. Similarly,
C2
and
C3
significantly reduced the immobility times in FST and TST, demonstrating their antidepressant properties. The biomarkers study revealed that these compounds significantly enhanced hippocampus CAT, SOD and GSH, and reduced MDA levels in the scopolamine-induced stress mice model. These findings suggest the potential of curcumin analogues (
C2
and
C3
) as antistress and antidepressant agents.