title: Neuroprotective Effects of 7, 8-dihydroxyflavone on Midbrain Dopaminergic Neurons in MPP+-treated Monkeys.
abstract: Parkinson's disease (PD) is one common neurodegenerative disease caused by a significant loss of midbrain dopaminergic neurons. Previous reports showed that 7, 8- dihydroxyflavone (7, 8-DHF) as a potent TrkB agonist can mimic BDNF and play neuroprotective roles for mouse dopaminergic neurons. Nonetheless, the safety and neuroprotective effects are unclear in monkey models of PD. Here, we find that 7, 8-DHF could be absorbed and metabolized into 7-hydroxy-8-methoxyflavone through oral administration in monkeys. The half-life time of 7, 8-DHF in monkey plasma is about 4-8 hrs. Furthermore, these monkeys maintain health state throughout the course of seven-month treatments of 7, 8-DHF (30 mg/kg/day). Importantly, 7, 8-DHF treatments can prevent the progressive degeneration of midbrain dopaminergic neurons by attenuating neurotoxic effects of MPP+and display strong neuroprotective effects in monkeys. Our study demonstrates that this promising small molecule may be transited into a clinical useful pharmacological agent.
authors.affiliation: Yunnan Key Laboratory of Primate Biomedical Research; Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, 650500, Yunnan, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: He
authors.affiliation: Yunnan Key Laboratory of Primate Biomedical Research; Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, 650500, Yunnan, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Xiang
authors.affiliation: Yunnan Key Laboratory of Primate Biomedical Research; Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, 650500, Yunnan, China.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Yunnan Key Laboratory of Primate Biomedical Research; Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, 650500, Yunnan, China.
authors.forename: Zongyong
authors.initials: Z
authors.lastname: Ai
authors.affiliation: Yunnan Key Laboratory of Primate Biomedical Research; Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, 650500, Yunnan, China.
authors.forename: Jingsong
authors.initials: J
authors.lastname: Shen
authors.affiliation: Yunnan Key Laboratory of Primate Biomedical Research; Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, 650500, Yunnan, China.
authors.forename: Tianzhuang
authors.initials: T
authors.lastname: Huang
authors.affiliation: Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030, China.
authors.forename: Liegang
authors.initials: L
authors.lastname: Liu
authors.affiliation: Yunnan Key Laboratory of Primate Biomedical Research; Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, 650500, Yunnan, China.
authors.forename: Weizhi
authors.initials: W
authors.lastname: Ji
authors.affiliation: Yunnan Key Laboratory of Primate Biomedical Research; Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, 650500, Yunnan, China.
authors.forename: Tianqing
authors.initials: T
authors.lastname: Li
mesh_terms: D000818:Animals; D059290:Dopaminergic Neurons / Q000378:metabolism* / Q000473:pathology; D044950:Flavanones / Q000494:pharmacology*; D020267:MPTP Poisoning / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008252:Macaca fascicularis; D008636:Mesencephalon / Q000378:metabolism* / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*
chemical_list: C478869:7,8-dihydroxyflavanone; D044950:Flavanones; D018696:Neuroprotective Agents