Bromelain Alleviates 3-Nitropropionic Acid-Induced Huntington's Disease-Like Symptoms in Rats Through the Interplay of SIRT1/PGC-1α and FOXO3a Pathways.

Bromelain, a combination of pineapple-derived enzymes, has demonstrated neuroprotective effects owing to its antioxidant and anti-inflammatory attributes. The current study intended to explore bromelain's neuroprotective impact against 3-nitropropionic acid (3-NP)-induced Huntington's disease (HD)-like symptoms in rats. Four groups of rats were randomly allocated: group 1 received saline; bromelain (40 mg/kg/i.p.) was given to groups 2 and 4 daily, whereas groups 3 and 4 received daily doses of 3-NP (10 mg/kg/i.p.) for 14 days. On the molecular level, bromelain administration resulted in upregulation of striatal SIRT-1, PGC-1α, TFAM and Nrf2 expression, enhancement of Akt phosphorylation, elevation of FOXO3a deacetylation and lessening of striatal oxidative stress damage by lowering MDA concentrations as well as raising the levels of NQO1, TAC, SOD and GSH. These effects were further substantiated by improvements in muscle strength, locomotor coordination, cognitive performance, and neuronal integrity. In conclusion, bromelain could be a beneficial neuroprotective candidate against HD-like aberrations experimentally induced by 3-NP.