title: Neuroprotective Effects of A Standardized Flavonoid Extract of Safflower Against Neurotoxin-Induced Cellular and Animal Models of Parkinson's Disease.
abstract: Safflower has long been used to treat cerebrovascular diseases in China. We previously reported that kaempferol derivatives of safflower can bind DJ-1, a protein associated with Parkinson's disease (PD), and flavonoid extract of safflower exhibited neuroprotective effects in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of PD. In this study, a standardized safflower flavonoid extract (SAFE) was isolated from safflower and mainly contained flavonoids. Two marker compounds of SAFE, kaempferol 3-O-rutinoside and anhydrosafflor yellow B, were proven to suppress microtubule destabilization and decreased cell area, respectively. We confirmed that SAFE in dripping pill form could improve behavioural performances in a 6-hydroxydopamine (6-OHDA)-induced rat model of PD, partially via the suppression of α-synuclein overexpression or aggregation, as well as the suppression of reactive astrogliosis. Using an MRI tracer-based method, we found that 6-OHDA could change extracellular space (ECS) diffusion parameters, including a decrease in tortuosity and the rate constant of clearance and an increase in the elimination half-life of the tracer in the 6-OHDA-lesioned substantia nigra. SAFE treatment could partially inhibit the changes in ECS diffusion parameters, which might provide some information about neuronal loss and astrocyte activation. Consequently, our results indicate that SAFE is a potential therapeutic herbal product for treatment of PD.
authors.affiliation: Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.|State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, China.
authors.forename: Rutong
authors.initials: R
authors.lastname: Ren
authors.affiliation: Beijing Key Lab of MRI Device and Technique, Beijing 100191, China.|Department of Radiology, Peking University Third Hospital, Beijing 100191, China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Shi
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Cao
authors.affiliation: Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.|State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.|State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.|State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, China.
authors.forename: Yongfei
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.|State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.|State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Lei
authors.affiliation: Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.|State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, China.
authors.forename: Hanjie
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.|State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, China.
authors.forename: Nuramatjan
authors.initials: N
authors.lastname: Ablat
authors.affiliation: Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.|State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, China.
authors.forename: Jiamin
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.|State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, China.
authors.forename: Wan
authors.initials: W
authors.lastname: Li
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, China.
authors.forename: Yingcong
authors.initials: Y
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, China.
authors.forename: Xianrong
authors.initials: X
authors.lastname: Qi
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, China.
authors.forename: Min
authors.initials: M
authors.lastname: Ye
authors.affiliation: Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.|State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Pu
authors.affiliation: Beijing Key Lab of MRI Device and Technique, Beijing 100191, China.|Department of Radiology, Peking University Third Hospital, Beijing 100191, China.
authors.forename: Hongbin
authors.initials: H
authors.lastname: Han
mesh_terms: D000818:Animals; D031187:Carthamus tinctorius / Q000737:chemistry*; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D005419:Flavonoids / Q000494:pharmacology*; D044949:Kaempferols / Q000737:chemistry / Q000494:pharmacology; D008279:Magnetic Resonance Imaging; D008297:Male; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D015394:Molecular Structure; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009498:Neurotoxins; D016627:Oxidopamine; D016716:PC12 Cells; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000517:prevention & control*; D010860:Pigments, Biological / Q000737:chemistry / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D051844:alpha-Synuclein / Q000378:metabolism
chemical_list: D005419:Flavonoids; D044949:Kaempferols; D018696:Neuroprotective Agents; D009498:Neurotoxins; D010860:Pigments, Biological; D010936:Plant Extracts; D051844:alpha-Synuclein; C000612029:anhydrosafflor yellow B; C492687:kaempferol-3-O-rutinoside; D016627:Oxidopamine