Kolaviron ameliorates behavioural deficit and injury to striatal dopaminergic terminals via modulation of oxidative burden, DJ-1 depletion and CD45R+ cells infiltration in MPTP-model of Parkinson's disease.

Parkinson's disease (PD) is the second most common neurodegenerative disease. Currently, the precise pathogenic detail of PD is not entirely clear and first line therapeutics fail to attenuate the progress of the disease. In this study, we examined the neuroprotective effect of kolaviron, a natural antioxidant and anti-inflammatory biflavonoid from Garcinia kola seed, on behavioural impairment, neurodegeneration, oxidative stress and neuroinflammation in an acute MPTP-induced PD model. Kolaviron mitigated the frequently interrupted MPTP-associated hyperkinesia, inefficient gait, immobility, inability to pay attention to sizable holes on walking path, habitual clockwise rotations characterized with minimal diversion of movements and impaired balance. Also, kolaviron suppressed MPTP-mediated striatal oxidative stress, depletion as well as degeneration of dopaminergic terminals, reduced DJ-1 secretion and upregulated expression of caspase-3. Kolaviron facilitated cytoprotective antioxidant response and prevented MPTP-mediated neuroinflammation by blocking striatal infiltration of peripheral CD45R positive cells. Additionally, kolaviron reversed MPTP-induced inhibition of acetylcholinesterase activity. Together, our study provides evidence that the neuroprotective capacity of kolaviron to modulate striatal degeneration, behavioural impairment, antioxidant/redox imbalance and neuroinflammation implicated in the pathogenesis of PD may involve upregulation of DJ-1 secretion and inhibition of CD45R cells infiltration. Our data recommend kolaviron as a possible neuroprotective strategy in the management of Parkinson's disease and the associated behavioural complications, albeit the identity of MPTP-associated striatal CD45R infiltrate needs to be further characterized.

Neuroprotective role of kolaviron in striatal redo-inflammation associated with rotenone model of Parkinson's disease.

Parkinson's disease is the most prevalent movement disorder. Currently, therapies are palliative with associated irreversible behavioural incompetence. Here, we investigated the ability of kolaviron (KV), an anti-inflammatory biflavonoid isolated form Garcinia kola seeds, to rescue striatal neuronal damage and redo-inflammation in rats exposed to rotenone (ROT). Aged rats exposed to 11 days of rotenone intoxication were treated with KV either concurrently or for 18 days. The 18-day regimen included 7 days of pre-treatment prior 11-day concurrent ROT-KV treatment. Rotenone-exposed rats lost weight appreciably and travelled less distance with reduced speed, decline efficiency to maintain a straight path, enhanced freezing, increased immobile episodes and poor hole recognition. The motor incompetence was attributed to enhanced striatal neurodegeneration, increased alpha synuclein formation and reduced tyrosine hydroxylase expression. ROT intoxication significantly increased reactive species production, which co-existed with induction of striatal antioxidant system and damage to biomolecules. ROT additionally upregulated COX-2 expression, enhanced myeloperoxidase activity and increased concentration of striatal inteleukine-6 (IL-6), IL-1ß and tumour necrosis factor (TNF-α). Treatment with kolaviron reversed the rotenone-associated locomotor impairment and exploratory deficits, motor/neuromuscular incompetence, striatal neurodegeneration, neurobiochemical imbalance, altered antioxidant defence system and neuroinflammation. KV-treated rats showed improved capacity to maintain efficient gait with minimal rigidity and enhanced coordination. Taken together, kolaviron exhibited neuroprotective properties, which may be beneficial for the prevention and management of Parkinson's disease, via antioxidant, anti-inflammatory and anti-apoptotic mechanisms.