Chrysin Ameliorated Neurochemical and Behavioural Changes Mediated By Combined Exposure of Interleukin-17 A With Amyloid Beta1-42 in Mice.

Abstract

Neuroinflammation is one of the major hallmarks of neurodegenerative diseases, including Alzheimer's disease (AD). Interleukin-17 (IL-17) cytokine and its downstream signaling have been shown to be implicated in preclinical and clinical models of AD. Moreover, the combination of recombinant IL-17 A with amyloid beta (Aβ_1-42) has been shown to be involved in promoting neuroinflammation during AD pathology. Hence, it is speculated that IL-17 may exacerbate Aβ_1-42-induced neuronal damage and inflammatory events in the brain. Although natural flavonoids have been reported to protect against neuroinflammation in AD, their role in IL-17 exacerbated Aβ_1-42-induced responses has not been reported previously. The current research explored the ability of Chrysin in regulating the exacerbation of neuronal damage and inflammation during AD pathology induced due to the combination of recombinant mouse IL-17 A (rmIL-17 A) with Aβ_1-42 in animals. Adult male BALB/c mice were exposed to intranasal Aβ_1-42 (5 µg/10µL in phosphate-buffered saline (PBS)/animal) and rmIL-17 (4 µg/kg in 10 µL PBS/animal) from day 1 to day 14 on alternate days with therapeutic oral administration of Chrysin suspension (100 mg/kg) during the last 7 days. Oral treatment with Chrysin demonstrated significant protective effects in improving the memory functions of the animals, along with the modulation of neurodegenerative and neuroinflammatory signalling, microglial and astrocytic activation, and redox balance in the hippocampus and cortex areas of the animal brain tissues. These results supported the neuroprotective ability of Chrysin against the exacerbation caused by rmIL-17 A in Aβ_1-42-induced AD in a mouse model.