title: Phloroglucinol attenuates motor functional deficits in an animal model of Parkinson's disease by enhancing Nrf2 activity.
abstract: In this study, we investigated whether phloroglucinol (1,3,5-trihydroxybenzene) has therapeutic effects in cellular and animal model of Parkinson's disease (PD). PD is the second most common, chronic and progressive neurodegenerative disease, and is clinically characterized with motor dysfunctions such as bradykinesia, rigidity, postural instability, gait impairment, and resting tremor. In the brains of PD patients, dopaminergic neuronal loss is observed in the Substantia nigra. Although the exact mechanisms underlying PD are largely unknown, mitochondrial dysfunction and oxidative stress are thought to be critical factors that induce the onset of the disease. Here, phloroglucinol administration was shown to attenuate motor functional deficits evaluated with rota-rod and apomorphine-induced rotation tests in 6-hydroxydopamine (6-OHDA)-induced PD animal models. Moreover, phloroglucinol ameliorated the loss of synapses as assessed with protein levels and immunoreactivity against synaptophysin in the midbrain region of the 6-OHDA-lesioned rats. In addition, in SH-SY5Y cultures, the cytotoxicity of 6-OHDA was reduced by pre-treatment with phloroglucinol. The increase in the reactive oxygen species, lipid peroxidation, protein carbonyl formation and 8-hydroxyguanine caused by treatment with 6-OHDA was attenuated by phloroglucinol in SH-SY5Y cells. Furthermore, phloroglucinol treatment rescued the reduced levels of nuclear Nrf2, antioxidant enzymes, i.e., catalase and glutathione peroxidase, in 6-OHDA-treated cells. Taken together, phloroglucinol has a therapeutic potential for treatment of PD.
authors: Department of Pharmacology and Biomedical Sciences, College of Medicine, Seoul National University, Seoul, Republic of Korea.
authors: Junghwa
authors: J
authors: Ryu
authors: Rui
authors: R
authors: Zhang
authors: Bo-Hyun
authors: BH
authors: Hong
authors: Eun-Jung
authors: EJ
authors: Yang
authors: Kyoung Ah
authors: KA
authors: Kang
authors: Moonseok
authors: M
authors: Choi
authors: Ki Cheon
authors: KC
authors: Kim
authors: Su-Jin
authors: SJ
authors: Noh
authors: Hee Soo
authors: HS
authors: Kim
authors: Nam-Ho
authors: NH
authors: Lee
authors: Jin Won
authors: JW
authors: Hyun
authors: Hye-Sun
authors: HS
authors: Kim
mesh_terms: D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology*; D002374:Catalase / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D015870:Gene Expression / Q000187:drug effects; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D006147:Guanine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008636:Mesencephalon / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009043:Motor Activity / Q000187:drug effects; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016627:Oxidopamine; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D010696:Phloroglucinol / Q000494:pharmacology*; D050050:Protein Carbonylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors; D013569:Synapses / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016708:Synaptophysin / Q000235:genetics / Q000378:metabolism
chemical_list: D000978:Antiparkinson Agents; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D017382:Reactive Oxygen Species; D016708:Synaptophysin; C024829:8-hydroxyguanine; D006147:Guanine; D016627:Oxidopamine; D010696:Phloroglucinol; D002374:Catalase; D005979:Glutathione Peroxidase
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