Morin ameliorates rotenone-induced Parkinson disease in mice through antioxidation and anti-neuroinflammation: gut-brain axis involvement

Parkinson's disease (PD) is the second most common neurodegenerative disorder affecting both motor and non motor functions. It is well reported that the neuropathological process leading to PD starts from the gut before spreading to the CNS affirming the role of environmental toxicants such as rotenone. Morin (3, 5, 7, 2 & PRIME;, 4 & PRIME;- pentahydroxyflavone) possesses neuroprotective and anti-oxidant activities which could be beneficial in PD. This study was designed to investigate the ameliorative influence of morin on rotenone-induced PD in mice. Male albino mice (18-23 g) were randomly divided into groups (n = 15) and treated for 28 consecutive days as follows: group 1: normal saline (10 ml/kg, p.o); group 2: rotenone (1 mg/kg, p.o, 0.5%w/v in CMC); groups 3-5: morin (5, 20 or 80 mg/kg, i.p.) + rotenone (1 mg/kg, p.o.), respectively, group 6: morin (20 mg/kg only, i.p.). Behavioural tasks were carried out weekly 1 h after treatments. Mice were euthanized on day 28 and discreet brain regions were assayed for oxidative stress parameters and immunohistochemical analysis. Morin reversed rotenone-induced behavioural deficits (motor incoordination, working memory deficit and depressive-like behaviour). Moreso, rotenone-induced lipid peroxidation (MDA), with a concomitant decrease in glutathione (GSH), superoxide dismutase (SOD) and acetylcholinesterase (AchE) activities in discreet regions of the brain were attenuated by the pre-treatment of mice with morin. Rotenone caused significant increase in the expression of iba-1, glial fibrillary acidic protein (GFAP), toll-like receptor 4 (TLR-4), and alpha-synuclein with a decrease in tyrosine hydroxylase positive neurons (TH) expression which were ameliorated by the pretreatment of mice with morin. Furthermore, rotenone-induced colon necrosis was reversed by morin administration. This study lend credence to the neuroprotective action of morin on rotenone-induced PD through enhancement of antioxidant defense and anti-inflammatory mechanisms.