Athzirys Alejandra Melecio-Hernández

Background: The plant-derived compound n-butylidenephthalide (BP) is an isobenzofuranone that has shown neuropharmacological effects on preclinical models of Parkinson’s, Alzheimer’s, and amyotrophic lateral sclerosis. Methods: This study evaluated the anti-inflammatory, antinociceptive, anxiolytic-like, hypnotic, anticonvulsant, and antidepressant-like effects of BP (50–200 mg/kg p.o.) using Balb/c mice in acute assays. This study also evaluated the antidepressant-like effects of BP in a mouse model of reserpine-induced depression-like behavior for 20 days. Inhibitors involved in the molecular process of depression and in silico studies were used to evaluate a possible mechanism of action for the antidepressant-like effects of BP. Results: BP induced low anti-inflammatory effects, showed low anticonvulsant effects, and lacked hypnotic effects or motor impairment in acute assays. The antidepressant-like effects of BP (100–200 mg/kg p.o.) were comparable to amitriptyline (25 mg/kg p.o.) in acute assays. The participation of serotonergic and adrenergic systems is involved in the acute antidepressant-like effects of BP. In the reserpine-induced depression model, BP (100 mg/kg p.o.) showed antidepressant-like effects in one of the two antidepressant tests, but with a lower effect than amitriptyline (20 mg/kg p.o.). Conclusions: BP (100 and 200 mg/kg) showed antidepressant-like effects in acute assays and, to a lesser extent, in a reserpine-induced chronic model of depression-like behavior.

Parkinson’s disease is the second most common neurodegenerative disease in the world. Natural products can offer a possible option of neuroprotective agents for preventing neurodegenerative diseases. D-Pinitol is a cyclic polyol with anxiolytic and antidepressant effects in acute assays. This work aimed to evaluate the effects of D-Pinitol (10, 50, and 100 mg/kg p.o.) in a chronic reserpine-induced depression model (19 days), using the forced swimming and tail suspension tests in female Balb/c mice, and the neuroprotective effects in an MPTP-induced Parkinsonism model (30 days) in male C57bL/6 mice, using behavioral tests such as wire grip, rotarod, catalepsy, and others. D-Pinitol showed low antidepressant-like effects in the reserpine-induced chronic depression model, compared to amitriptyline (25 mg/kg p.o.). D-Pinitol protected MPTP-treated mice from motor impairment with similar effects to those shown by L-Dopa (25 mg/kg p.o.) as evaluated in different behavioral tests. The inhibition of oxidative stress markers, increase in dopamine levels, and avoidance of apoptosis in neuronal cells were the mechanisms by which D-Pinitol protects MPTP-treated mice from motor impairment.