Cajanus cajan (L) Millsp seeds extract prevents rotenone-induced motor- and non-motor features of Parkinson disease in mice: Insight into mechanisms of neuroprotection.

ETHNOPHARMACOLOGICAL RELEVANCE: Cajanus cajan (L) Millsp (Fabaceae) seed decoction is used by traditional healers in Nigeria as nerve tonic, hence, could be beneficial in the treatment of Parkinson's disease (PD), a progressive and debilitating neurodegenerative disease that imposes great burden on the healthcare system globally. AIM OF THE STUDY: This study aimed at investigating the neuroprotective effect of ethanol seed extract of Cajanus cajan (CC) in the treatment of rotenone-induced motor symptoms and non-motor symptoms associated with PD. MATERIALS AND METHODS: To assess the protective action of CC on rotenone-induced motor- and non-motor symptoms of PD, mice were first pretreated with CC (50, 100 or 200 mg/kg, p.o.) an hour before oral administration of rotenone (1 mg/kg, p.o, 0.5% in carboxyl-methylcellulose) for 28 consecutive days and weekly behavioural tests including motor assessment (open field test (OFT), rotarod, pole and cylinder tests) and non-motor assessment (novel object recognition (NOR), Y-maze test (YM), forced swim and tail suspension, gastric emptying and intestinal fluid accumulation tests) were carried out. The animals were euthanized on day 28 followed by the collection of brain for assessment of oxidative stress, inflammatory markers and immunohistochemical analysis of the striatum (STR) and substantia nigra (SN). Phytochemicals earlier isolated from CC were docked with protein targets linked with PD pathology such as; catechol-O-methyltransferase (COMT), tyrosine hydroxylase (TH) and Leucine rich receptor kinase (LRRK). RESULTS: this study showed that CC significantly reduced rotenone-induced spontaneous motor impairment in OFT, pole, cylinder and rotarod tests in mice as well as significant improvement in non-motor features (significant reversal of rotenone-induced deficits discrimination index and spontaneous alternation behaviour in NORT and YM test, respectively, reduction in immobility time in forced swim/tail suspension test, gastrointestinal disturbance in intestinal transit time in mice. Moreso, rotenone-induced neurodegeneration, oxidative stress and neuroinflammation were significantly attenuated by CC administration. In addition, docking analysis showed significant binding affinity of CC phytochemicals with COMT, TH and LRRK2 receptors. CONCLUSION: Cajanus cajan seeds extract prevented both motor and non-motor features of Parkinson disease in mice through its antioxidant and anti-inflammatory effects. Hence, could be a potential phytotherapeutic adjunct in the management of Parkinson disease.

Datura stramonium abrogates depression- and anxiety-like disorders in mice: possible involvement of monoaminergic pathways in its antidepressant activity.

OBJECTIVES: Ethno-botanical surveys uncovered the use of Datura stramonium in the management of mental health abnormalities. Antidepressant- and anxiolytic-like activities of hydroethanol leaf extract of D. stramonium (HLDS) in mice and its possible mechanism of action were investigated in this study. METHODS: The hole-board test (HBT), open field test (OFT), elevated plus maze test (EPMT), and social interaction test (SIT) were used to investigate the anxiolytic-like activity while forced swim test (FST) and tail suspension test (TST) were employed for the antidepressant effect. Mice were pre-treated orally with purified water (10 mL/kg), bromazepam (1 mg/kg), fluoxetine (20 mg/kg) and D. stramonium (25, 50, 100 and 200 mg/kg). One hour post-treatment, mice were subjected to the various tests. RESULTS: In HBT, D. stramonium increased the head dips and sectional crossings turnover. D. stramonium increased the number of square crossed and rearings/assisted rearings in OFT. DS increased the time spent in open arms of EPM. In SIT, D. stramonium increased the frequency/duration of interactions. In FST and TST, D. stramonium decreased the duration of immobility which were reversed by doxazosin (α1 adrenoceptor antagonist) and ondasentron (5-HT3 receptor antagonist). CONCLUSIONS: HLDS has anxiolytic- and antidepressant-like activities through modulation of serotoninergic and adrenergic neurotransmissions.