title: Ginsenoside Re and Rd enhance the expression of cholinergic markers and neuronal differentiation in Neuro-2a cells.
abstract: In Alzheimer's disease (AD), extensive neuronal loss and a deficiency of the neurotransmitter acetylcholine (ACh) are the major characteristics during pathogenesis in the brain. In the present study, we aimed to investigate whether representative ginsenosides from ginseng can regulate choline acetyltransferase (ChAT) and vesicular acetylcholine transporter (VAChT), which are required for cholinergic neurotransmission. Our results revealed that Re and Rd induced effectively the expression of ChAT/VAChT genes in Neuro-2a cells as well as ACh elevation. Microtubule-associated protein-2 (MAP-2), nerve growth factor receptor (p75), p21, and TrkA genes and proteins were also significantly expressed. Moreover, both activated extracelullar signal-regulated protein kinase (ERK) and Akt were inhibited by K252a, a selective Trk receptor inhibitor. These findings strongly indicate that Re and Rd play an important role in neuronal differentiation and the nerve growth factor (NGF)-TrkA signaling pathway. High performance liquid chromatography analysis showed that Re and Rd administered orally were transported successfully into brain tissue and increased the level of ChAT and VAChT mRNA. The present study demonstrates that Re and Rd are selective candidates for upregulation of the expression of cholinergic markers, which may counter the symptoms and progress of AD.
authors.affiliation: College of Pharmacy, Chung-Ang University.
authors.forename: Min Soo
authors.initials: MS
authors.lastname: Kim
authors.forename: Jung Min
authors.initials: JM
authors.lastname: Yu
authors.forename: Hee Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: Hae Bok
authors.initials: HB
authors.lastname: Kim
authors.forename: Seung Tae
authors.initials: ST
authors.lastname: Kim
authors.forename: Su Kil
authors.initials: SK
authors.lastname: Jang
authors.forename: Young Wook
authors.initials: YW
authors.lastname: Choi
authors.forename: Do Ik
authors.initials: DI
authors.lastname: Lee
authors.forename: Seong Soo
authors.initials: SS
authors.lastname: Joo
mesh_terms: D000109:Acetylcholine / Q000096:biosynthesis*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D002795:Choline O-Acetyltransferase / Q000096:biosynthesis; D005786:Gene Expression Regulation / Q000187:drug effects*; D036145:Ginsenosides / Q000493:pharmacokinetics / Q000494:pharmacology*; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis; D009474:Neurons / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D020800:Receptor, Nerve Growth Factor / Q000096:biosynthesis; D020917:Receptor, trkA / Q000096:biosynthesis; D050494:Vesicular Acetylcholine Transport Proteins / Q000096:biosynthesis; D020741:rho GTP-Binding Proteins / Q000096:biosynthesis
chemical_list: D015415:Biomarkers; D036145:Ginsenosides; D008869:Microtubule-Associated Proteins; D020800:Receptor, Nerve Growth Factor; D050494:Vesicular Acetylcholine Transport Proteins; C097367:ginsenoside Rg3; C049864:ginsenoside Re; C442759:ginsenoside Rb1; D002795:Choline O-Acetyltransferase; D020917:Receptor, trkA; D020741:rho GTP-Binding Proteins; D000109:Acetylcholine; C035054:ginsenoside Rg1; C049863:ginsenoside Rd