title: Protection effect of piperine and piperlonguminine from Piper longum L. alkaloids against rotenone-induced neuronal injury.
abstract: 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.
authors.affiliation: Center of Parkinson׳s Disease Beijing Institute for Brain Disorders, Key Laboratory for Neurodegenerative Disease of the Ministry of Education, Department of Neurobiology Capital Medical University, Beijing 100069, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.affiliation: Center of Parkinson׳s Disease Beijing Institute for Brain Disorders, Key Laboratory for Neurodegenerative Disease of the Ministry of Education, Department of Neurobiology Capital Medical University, Beijing 100069, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.affiliation: Center of Parkinson׳s Disease Beijing Institute for Brain Disorders, Key Laboratory for Neurodegenerative Disease of the Ministry of Education, Department of Neurobiology Capital Medical University, Beijing 100069, China.
authors.forename: Ge
authors.initials: G
authors.lastname: Gao
authors.affiliation: Center of Parkinson׳s Disease Beijing Institute for Brain Disorders, Key Laboratory for Neurodegenerative Disease of the Ministry of Education, Department of Neurobiology Capital Medical University, Beijing 100069, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Wu
authors.affiliation: Center of Parkinson׳s Disease Beijing Institute for Brain Disorders, Key Laboratory for Neurodegenerative Disease of the Ministry of Education, Department of Neurobiology Capital Medical University, Beijing 100069, China.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Center of Parkinson׳s Disease Beijing Institute for Brain Disorders, Key Laboratory for Neurodegenerative Disease of the Ministry of Education, Department of Neurobiology Capital Medical University, Beijing 100069, China. Electronic address: huiyang@ccmu.edu.cn.
authors.forename: Hui
authors.initials: H
authors.lastname: Yang
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001343:Autophagy / Q000187:drug effects / Q000502:physiology; D052117:Benzodioxoles / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D004148:Dioxolanes / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D006801:Humans; D008297:Male; D051379:Mice; D033681:Mitochondrial Membrane Transport Proteins / Q000187:drug effects* / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D020734:Parkinsonian Disorders / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D008517:Phytotherapy; D031701:Piper; D010880:Piperidines / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology; D053284:Polyunsaturated Alkamides / Q000494:pharmacology*; D011897:Random Allocation; D017208:Rats, Wistar; D012402:Rotenone; D010881:Piperidones
chemical_list: D000470:Alkaloids; D000978:Antiparkinson Agents; D052117:Benzodioxoles; D004148:Dioxolanes; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D018696:Neuroprotective Agents; D010880:Piperidines; D010936:Plant Extracts; D053284:Polyunsaturated Alkamides; D012402:Rotenone; C498077:piperlongumine; D010881:Piperidones; C008922:piperine
keywords: Mitochondrial permeability transition pore; Parkinson׳s disease; Treatment