Evaluation of Antioxidant, Anti-inflammatory, and Cytotoxic Activities of Crotalaria pallida Aiton Leaves

Objective: To investigate the effect of EL hydroalcoholic extract (ELHA) against lipopolysachharide (LPS)‑induced depressive‑like behavior and neurochemical alterations in mice. Materials and Methods: Mice were pretreated with vehicle, imipramine (10 mg/kg, intraperitoneally [i. p.]), and ELHA (100 and 200 mg/ kg, per oral) for 14 days, and depressive‑like behavior was induced by LPS (0.83 mg/kg, i. p.). Depressive‑like behavior in mice was evaluated by open‑field test, forced swimming test (FST), and tail suspension test (TST). Cytokines (tumor necrosis factor‑alpha [TNF‑α], interleukin‑1β [IL‑1β], IL‑6, and IL‑10), BDNF, monoamines (noradrenaline [NA], dopamine, 5‑hydroxy), and oxido‑nitrosative stress parameters (lipid peroxidation [LPO], glutathione [GSH], GSH peroxidase [GPx], catalase [CAT], superoxide dismutase [SOD], nitric oxide) were measured in the hippocampus (HC). Hippocampal caspase‑3, nuclear factor‑kappa B phosphor 65 (NF‑κB p65), nuclear‑related factor 2 (Nrf2), and TrkB and BDNF levels were measured by reverse transcriptase‑polymerase chain reaction (RT‑PCR) and immunoblotting. Results: Liquid chromatography‑electrospray ionization‑mass spectroscopy (MS)/MS analysis revealed the presence of ambrosin, friedelin, flavone, scopoletin, and luteolin in ELHA. ELHA showed significant antidepressant‑like effect by decreasing the immobility time in FST and TST in LPS‑challenged mice. Moreover, ELHA significantly attenuated TNF‑α, IL‑1β, IL‑6, and LPO levels in LPS‑challenged mice, whereas LPS‑induced decrease in hippocampal IL‑10, BDNF, GSH, GPx, CAT, SOD, and monoamine levels was also restored significantly by ELHA. RT‑PCR and immunobloting results showed that ELHA significantly attenuated the upregulation of Caspase‑3, NF‑κB, p65, and Nrf2 and downregulation of TrkB and BDNF levels in the HC of LPS‑challenged mice. Conclusion: The findings demonstrated antidepressant‑like action of ELHA which could be due to the inhibition of neuroinflammation, oxido‑nitrosative stress, and upregulation of TrkB‑BDNF and monoaminergic pathways in the HC.