title: Discovery of novel anti-parkinsonian effect of schisantherin A in in vitro and in vivo.
abstract: Dibenzocyclooctadiene lignans represent a unique group of natural chemical structures, are considered as protectants against neuronal cell death and cognitive impairment in neurological disorders. Among the family of dibenzocyclooctadiene lignan analogs from the fruit of Schisandra chinensis (Turcz.) Baill, neuroprotective potential of schisantherin A (StA) has not yet been characterized. In this study, 1-methyl-4-phenylpyridinium ion (MPP(+))-incubated SH-SY5Y cells and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice were used to study the neuroprotection of StA. Pretreatment with StA significantly inhibited MPP(+)-induced cytotoxicity in SH-SY5Y cells. Moreover, StA conferred significant protection against MPTP-induced loss of TH-positive dopaminergic neurons in a Parkinson's disease (PD) mice model. Structure activity relationship analysis suggested that methylenedioxy, benzoyloxy and methoxyl groups, in the dibenzocyclooctadiene lignan of StA, were probably functionally important to its neuroprotective activity. In addition, Western blotting analysis demonstrated that StA exhibited neuroprotection against MPP(+) through the regulation of two distinct pathways including increasing CREB-mediated Bcl-2 expression and activating PI3K/Akt survival signaling suggesting that StA might be a promising neuroprotective agent for the prevention of PD.
authors.affiliation: State Key Laboratory of Quality Research of Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Sa
authors.affiliation: State Key Laboratory of Quality Research of Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao, China.
authors.forename: Lun Qing
authors.initials: LQ
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Quality Research of Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao, China.
authors.forename: Cheong Meng
authors.initials: CM
authors.lastname: Chong
authors.affiliation: Institute of New Drug Research, Guangdong Province Key Laboratory of Pharmacodynamic, Constituents of Traditional Chinese Medicine & New Drug Research, College of Pharmacy, Jinan University, Guangdong, China.
authors.forename: Bao Jian
authors.initials: BJ
authors.lastname: Guo
authors.affiliation: Institute of New Drug Research, Guangdong Province Key Laboratory of Pharmacodynamic, Constituents of Traditional Chinese Medicine & New Drug Research, College of Pharmacy, Jinan University, Guangdong, China.
authors.forename: Sai
authors.initials: S
authors.lastname: Li
authors.affiliation: State Key Laboratory of Quality Research of Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao, China; Institute of New Drug Research, Guangdong Province Key Laboratory of Pharmacodynamic, Constituents of Traditional Chinese Medicine & New Drug Research, College of Pharmacy, Jinan University, Guangdong, China. Electronic address: zaijunzhang@163.com.
authors.forename: Zai Jun
authors.initials: ZJ
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Quality Research of Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: State Key Laboratory of Quality Research of Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao, China.
authors.forename: Pui Man
authors.initials: PM
authors.lastname: Hoi
authors.affiliation: State Key Laboratory of Quality Research of Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao, China. Electronic address: simonlee@umac.mo.
authors.forename: Simon Ming Yuen
authors.initials: SM
authors.lastname: Lee
mesh_terms: D015655:1-Methyl-4-phenylpyridinium; D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D034242:Cyclooctanes / Q000494:pharmacology*; D004149:Dioxoles / Q000494:pharmacology*; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000473:pathology; D006801:Humans; D017705:Lignans / Q000494:pharmacology*; D008297:Male; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010300:Parkinson Disease / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D000978:Antiparkinson Agents; C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D034242:Cyclooctanes; D004149:Dioxoles; D017705:Lignans; D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; C034557:schizandrer A; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D015655:1-Methyl-4-phenylpyridinium
keywords: Bcl-2; Dibenzocyclooctadiene lignans; Neuroprotection; Schisantherin A