title: Hydroxysafflor Yellow A Improves Motor Dysfunction in the Rotenone-Induced Mice Model of Parkinson's Disease.
abstract: Dopamine D3 receptor (DRD3) is diminished in patients of Parkinson's disease (PD). Brain-derived neurotrophic factor (BDNF) is responsible for regulating expression of the DRD3 in the brain. Our previous study showed that hydroxysafflor yellow A (HSYA) could increase BDNF content in the striatum of PD mice. This experiment aimed to evaluate whether HSYA can improve the motor dysfunction induced by rotenone through regulating the BDNF/TrkB/DRD3 signaling pathway in mice. Male C57/BL6 mice were intraperitoneally treated with HSYA. Thirty minutes later, they were intragastrically administered with rotenone at a dose of 30 mg/kg. Pole, rotarod and open field tests were investigated at 28 d. Then, tyrosine hydroxylase (TH) in substantia nigra was observed by immunohistochemistry. Dopamine content was detected by high-performance liquid chromatography. The expressions of BDNF, phospho-tropomyosin-related kinase B (p-TrkB), tropomyosin-related kinase B (TrkB), phospho-phosphoinositide 3-kinase (p-PI3K), phosphoinositide 3-kinase (PI3K), phospho-protein kinase B (p-AKT), protein kinase B (AKT), and DRD3 were assayed by western blotting. Behavioral tests showed that rotenone-challenged mice displayed motor dysfunction. However, treatment with HSYA improved motor dysfunction induced by rotenone. HSYA treatment increased not only the number of TH-containing dopaminergic neurons in substantia nigra, but also the dopamine content in the striatum in PD mice. Moreover, the expressions of BDNF, p-TrkB/TrkB, DRD3, p-PI3K/PI3K, p-AKT/AKT were significantly increased in rotenone plus HSYA group. Our results indicated that HSYA improved motor dysfunction in rotenone-induced PD model and the pharmacological action of HSYA was related to regulating BDNF/TrkB/DRD3 signaling pathway, at least, in part.
authors.affiliation: School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, 264005, Yantai, Shandong, People's Republic of China.
authors.forename: Tian
authors.initials: T
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, 264005, Yantai, Shandong, People's Republic of China.
authors.forename: Lijie
authors.initials: L
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, 264005, Yantai, Shandong, People's Republic of China.
authors.forename: Cuiting
authors.initials: C
authors.lastname: Li
authors.affiliation: Center of Mitochondria and Healthy Aging, School of Life Science, Yantai University, 264005, Yantai, Shandong, People's Republic of China.
authors.forename: Bing
authors.initials: B
authors.lastname: Han
authors.affiliation: Center of Mitochondria and Healthy Aging, School of Life Science, Yantai University, 264005, Yantai, Shandong, People's Republic of China.
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Center of Mitochondria and Healthy Aging, School of Life Science, Yantai University, 264005, Yantai, Shandong, People's Republic of China.
authors.forename: Ji
authors.initials: J
authors.lastname: Li
authors.affiliation: Center of Mitochondria and Healthy Aging, School of Life Science, Yantai University, 264005, Yantai, Shandong, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Lv
authors.affiliation: Center of Mitochondria and Healthy Aging, School of Life Science, Yantai University, 264005, Yantai, Shandong, People's Republic of China.
authors.forename: Shuyun
authors.initials: S
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, 264005, Yantai, Shandong, People's Republic of China. fufenghua@sohu.com.
authors.forename: Fenghua
authors.initials: F
authors.lastname: Fu
mesh_terms: D000818:Animals; D002599:Chalcone / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D004298:Dopamine / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019957:Motor Skills Disorders / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D020734:Parkinsonian Disorders / Q000139:chemically induced* / Q000188:drug therapy* / Q000378:metabolism; D010860:Pigments, Biological / Q000494:pharmacology / Q000627:therapeutic use; D011809:Quinones / Q000494:pharmacology / Q000627:therapeutic use*; D011897:Random Allocation; D045442:Rotarod Performance Test / Q000379:methods; D012402:Rotenone / Q000633:toxicity*
chemical_list: D010860:Pigments, Biological; D011809:Quinones; D012402:Rotenone; C085278:hydroxysafflor yellow A; D002599:Chalcone; D004298:Dopamine
keywords: Brain-derived neurotrophic factor; Dopamine D3 receptor; Hydroxysafflor Yellow A; Motor dysfunction; Parkinson’s disease