Protective Effects of Cubebin on Neuroinflammation, Neurotransmitter Depletion, Mitochondrial Dysfunction, and Motor Disability in Parkinsonian Rats

Abstract

Parkinson’s disease (PD) is an advanced neurodegenerative state with diverse degeneration of dopaminergic neurons, oxidative stress, mitochondrial dysfunction, and neuroinflammation. The present study aimed to evaluate the neuroprotective effect of cubebin against rotenone-induced Parkinsonism disability in Wistar rats. The animals were divided into four groups: the normal control group, the rotenone group, and the cubebin groups (10 and 20 mg/kg, p.o.) with rotenone for 28 days. Behavioural, biochemical, neurochemical, mitochondrial, and histopathological tests were conducted, using an open field test, a rotarod, catalepsy, grip strength, and akinesia tests. The motor deficits induced by rotenone administration were significant, and there was oxidative stress, a rise in nitrite levels, an increase in pro-inflammatory cytokines [tumour necrosis factor-α, interleukin (IL)-1β, IL-6, and nuclear factor-kappa B], mitochondrial dysfunction, and loss of dopamine (DA) and serotonin content. Cubebin treatment significantly reduced locomotor and motor coordination deficits, as well as catalepsy and akinesia. It was effective in restoring endogenous antioxidant defence in the form of an increase in superoxide dismutase, catalase, and glutathione and decreased malondialdehyde and nitrite accumulation. Cubebin also reduced neuroinflammatory markers and restored neurotransmitter levels, including DA, serotonin, glutamate, 3,4-dihydroxyphenylacetic acid, and homovanillic acid. Histopathological evaluation revealed good maintenance of neuronal architecture in cubebin-treated animals when compared with rats treated with rotenone. Cubebin was unable to fully correct inhibition of mitochondrial complexes I and II, but it was observed to dampen downstream oxidative and inflammatory pathways linked to neuronal degeneration. Based on these results, it is believed that cubebin may be an essential medicinal substance for the management of PD due to its anti-inflammatory and antioxidant properties, which also protect the nervous system from the effects of rotenone.