title: Distinctive effect on nerve growth factor-induced PC12 cell neurite outgrowth by two unique neolignan enantiomers from Illicium merrillianum.
abstract: Merrillianoid (1), a racemic neolignan possessing the characteristic benzo-2,7-dioxabicyclo[3.2.1]octane moiety, was isolated from the branches and leaves of Illicium merrillianum. Chiral separation of 1 gave two enantiomers (+)-1 and (-)-1. The structure of 1 was established by comprehensive spectroscopic analysis and single crystal X-ray diffraction. The absolute configurations of enantiomers were determined by quantum mechanical calculation. Compound (+)-1 exhibited a better neurotrophic activity than racemate 1 by promoting nerve growth factor (NGF) induced PC12 cell neurite outgrowth, while (-)-1 showed a distinctive inhibitory effect. Furthermore, a mechanism study indicated that the two enantiomers influenced NGF-induced neurite outgrowth of PC12 cells possibly by interacting with the trkA receptor, and extracellular signal regulated kinases 1/2 (ERK1/2) and mitogen-activated protein kinase (MEK) in Ras/ERK signal cascade. But the phosphorylation level of serine/threonine kinase Akt1 and Akt2 in PI3K/Akt signal pathway showed no significant difference between (+)-1 and (-)-1.
authors.affiliation: Department of Phytochemistry, School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, P. R. China.
authors.forename: Xinhui
authors.initials: X
authors.lastname: Tian
authors.affiliation: School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, P. R. China.
authors.forename: Rongcai
authors.initials: R
authors.lastname: Yue
authors.affiliation: Department of Phytochemistry, School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, P. R. China.
authors.forename: Huawu
authors.initials: H
authors.lastname: Zeng
authors.affiliation: School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, P. R. China.
authors.forename: Honglin
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Phytochemistry, School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, P. R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Shan
authors.affiliation: School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, P. R. China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: He
authors.affiliation: Department of Phytochemistry, School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, P. R. China.
authors.forename: Yunheng
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Department of Phytochemistry, School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, P. R. China.|School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, P. R. China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D002942:Circular Dichroism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D029523:Illicium / Q000737:chemistry*; D017705:Lignans / Q000737:chemistry / Q000494:pharmacology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D015394:Molecular Structure; D009414:Nerve Growth Factors / Q000494:pharmacology*; D016501:Neurites / Q000187:drug effects* / Q000502:physiology; D016716:PC12 Cells; D051381:Rats; D020917:Receptor, trkA / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013237:Stereoisomerism; D014961:X-Ray Diffraction; D018631:ras Proteins / Q000378:metabolism
chemical_list: D017705:Lignans; D009414:Nerve Growth Factors; D020917:Receptor, trkA; D048049:Extracellular Signal-Regulated MAP Kinases; D020928:Mitogen-Activated Protein Kinases; D018631:ras Proteins