Protective effects of diacerein against quinolinic acid-induced Huntington's disease-like symptoms in adult zebrafish by targeting GSK-3β signalling.

Abstract

Huntington's disease is a brain-related hereditary condition characterized by a gradual loss of mental, physical, and emotional function. Quinolinic acid is a toxic substance that is formed because of the breakdown of tryptophan, a compound involved in the metabolism of the amino acid. Diacerein is an anthraquinone which shows anti-inflammatory effects. The binding capacity of diacerein on GSK-3β is screened via Auto Dock. The purpose of the study is to check neuroprotective and anti-inflammatory properties of diacerein on QA-induced HD in adult zebra fish. In this study, 14 fish in each group were used, QA was administered by i.c.v. route as a toxin on the day 0, and diacerein (25 and 50 mg/kg) as treatment and tetrabenazine as standard were used for 14 days. We have performed three neurobehavioral parameters such as open-field (for locomotion), T-maze (for memory), and novel diving test (for anxiety), followed by biochemical parameters such as total protein estimation, LPO, GSH, nitrite, AChEs, and catalase, neurotransmitters (GABA and glutamate) along with inflammatory markers (IL-1β, TNF-α, and IL-17), and histopathological evaluation at the end. Diacerein enhances motor function, modulates neurotransmitter levels, diminishes oxidative stress markers, controls the generation of inflammatory cytokines, and inhibits GSK-3β activity. Furthermore, diacerein improves the neurotoxicity and neurobehavioral impairments in adult zebra fish with Huntington's disease-like symptoms caused by quinolinic acid.