piperine and Parkinsonian-Disorders

Currently available treatment approaches for Parkinson׳s disease (PD) are limited in terms of variety and efficacy. Piper longum L. (PLL; Piperaceae) is used in traditional medicine in Asia and the Pacific Islands, with demonstrated anti-inflammatory and antioxidant activities in preclinical studies, and alkaloid extracts of PLL have shown protective effects in PD models. The present study investigated the mechanistic basis for the observed protective effects of PLL. Rats treated with PLL-derived alkaloids showed improvement in rotenone-induced motor deficits, while reactive oxygen species (ROS) production was decreased, mitochondrial membrane potential was stabilized, and the opening of the mitochondrial permeability transition pore (mPTP)-which is involved in ROS production-was inhibited. In addition, rotenone-induced apoptosis was abrogated in the presence of these alkaloids, while a pretreatment stimulated autophagy, likely mitigating neuronal injury by the removal of damaged mitochondria. These findings provide novel insight into the neuroprotective function of PLL as well as evidence in favor of its use in PD treatment. This article is part of a Special Issue entitled SI: Neuroprotection.

Topics: Alkaloids; Animals; Antiparkinson Agents; Apoptosis; Autophagy; Benzodioxoles; Brain; Cell Line; Dioxolanes; Drug Evaluation, Preclinical; Humans; Male; Mice; Mitochondrial Membrane Transport Proteins; Mitochondrial Permeability Transition Pore; Neurons; Neuroprotective Agents; Parkinsonian Disorders; Phytotherapy; Piper; Piperidines; Plant Extracts; Polyunsaturated Alkamides; Random Allocation; Rats, Wistar; Rotenone

Parkinson's disease (PD) is the most widespread form of dementia where there is an age related degeneration of dopaminergic neurons in the substantia nigra region of the brain. Accumulation of α-synuclein (αS) protein aggregate, mitochondrial dysfunction, oxidative stress, and neuronal cell death are the pathological hallmarks of PD. In this context, amalgamation of curcumin and piperine having profound cognitive properties, and antioxidant activity seems beneficial. However, the blood-brain barrier (BBB) is the major impediment for delivery of neurotherapeutics to the brain. The present study involves formulation of curcumin and piperine coloaded glyceryl monooleate (GMO) nanoparticles coated with various surfactants with a view to enhance the bioavailability of curcumin and penetration of both drugs to the brain tissue crossing the BBB and to enhance the anti-parkinsonism effect of both drugs in a single platform. In vitro results demonstrated augmented inhibition of αS protein into oligomers and fibrils, reduced rotenone induced toxicity, oxidative stress, and apoptosis, and activation of autophagic pathway by dual drug loaded NPs compared to native counterpart. Further, in vivo studies revealed that our formulated dual drug loaded NPs were able to cross BBB, rescued the rotenone induced motor coordination impairment, and restrained dopaminergic neuronal degeneration in a PD mouse model.

Topics: Alkaloids; alpha-Synuclein; Animals; Antiparkinson Agents; Benzodioxoles; Blood-Brain Barrier; Capillary Permeability; Curcumin; Drug Delivery Systems; Drug Therapy, Combination; Liposomes; Male; Mice, Inbred BALB C; Mice, Inbred C57BL; Nanoparticles; Neuroprotective Agents; Parkinsonian Disorders; PC12 Cells; Piperidines; Polyunsaturated Alkamides; Protein Aggregation, Pathological; Random Allocation; Rats; Rotenone; Surface-Active Agents