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

• Published in: Neurotoxicology (Park Forest South) 2019-07, Vol.73, p.132-141
• Main Authors: Farombi, Ebenezer O., Awogbindin, Ifeoluwa O., Farombi, Temitope H., Oladele, Johnson O., Izomoh, Edirin R., Aladelokun, Oladimeji B., Ezekiel, Ibukunoluwa O., Adebambo, Oluwabunmi I., Abah, Victoria O.
• Format: Article
• Language: English
• Subjects: alpha-Synuclein - metabolism; Animals; Anti-Inflammatory Agents - pharmacology; Antioxidants; Antiparkinson Agents - pharmacology; Apoptosis; Apoptosis - drug effects; Behavior, Animal - drug effects; Biomolecules; Corpus Striatum - drug effects; Corpus Striatum - metabolism; Corpus Striatum - pathology; Corpus Striatum - physiopathology; Cyclooxygenase-2; Cytokines - metabolism; Disease control; Disease Models, Animal; Exploratory Behavior - drug effects; Exposure; Flavonoids - pharmacology; Freezing; Gait; Hydroxylase; IL-1β; Inflammation Mediators - metabolism; Interleukin 6; Intoxication; Kolaviron; Locomotion - drug effects; Male; Movement disorders; Neostriatum; Neurobehavioural deficits; Neurodegeneration; Neurodegenerative diseases; Neurons - drug effects; Neurons - metabolism; Neurons - pathology; Neuroprotection; Neuroprotective Agents - pharmacology; Oxidative Stress - drug effects; Parkinson's disease; Parkinsonian Disorders - chemically induced; Parkinsonian Disorders - drug therapy; Parkinsonian Disorders - metabolism; Parkinsonian Disorders - pathology; Peroxidase; Rats, Wistar; Reactive Oxygen Species - metabolism; Rigidity; Rot; Rotenone; Seeds; Striatal redo-inflammation; Synuclein; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Tumors; Tyrosine; Tyrosine 3-monooxygenase; Tyrosine 3-Monooxygenase - metabolism; Tyrosine hydroxylase
• ISSN: 0161-813X; 1872-9711
• DOI: 10.1016/j.neuro.2019.03.005

•Treatment of rotenone-exposed rats with kolaviron conferred neuroprotection.•Kolaviron mitigated ROT-induced neuromuscular incompetence and exploratory deficits.•Kolaviron improved capacity to maintain efficient gait and coordination with minimal rigidity.•Kolaviron prevented striatal neurodegeneration, neurobiochemical imbalance and neuroinflammation.•Kolaviron treatment was more potent in preventing progressive neurodegeneration. 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-1β 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.