title: Chronic administration of anti-stroke herbal medicine TongLuoJiuNao reduces amyloidogenic processing of amyloid precursor protein in a mouse model of Alzheimer's disease.
abstract: Composed of Ginsenoside Rg1 and Geniposide, the herbal medicine TongLuoJiuNao (TLJN) injection liquid has anti-inflammatory properties and can improve learning and memory in mice. Recently, TLJN has been used to treat the patients with cerebral ischemic stroke and vascular dementia, which significantly increase the risk of developing Alzheimer's disease (AD) in the early human beings. Although beneficial effects of TLJN have been reported in the vascular-associated brain disorders, the roles of TLJN in AD brains are still not clear. In this study, we chronically administered TLJN in amyloid precursor protein (APP) Swedish mutant transgenic mice (APP23) from 6 months old of age, which is at the onset of Aβ plaques, to 12 months old. We found that TLJN significantly decreased Aβ production and deposition in the brain of APP23 mice. Furthermore, we observed that TLJN down-regulated the levels and activity of β-secretase 1 (BACE1) protein as well as the expression levels of γ-secretase complex components: PS1, nicastrin and anterior pharynx-defective 1 (APH1) but not presenilin enhancer 2 (PEN2). The results suggest an inhibitory effect of TLJN on amyloidogenic APP processing by down-regulating the cleavage enzymes BACE1 and γ-secretase.
authors.affiliation: Center for Advanced Therapeutic Strategies of Brain Disorders, Roskamp Institute, Sarasota, Florida, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: He
authors.forename: Pengtao
authors.initials: P
authors.lastname: Li
authors.forename: Qian
authors.initials: Q
authors.lastname: Hua
authors.forename: Yuan
authors.initials: Y
authors.lastname: Liu
authors.forename: Matthias
authors.initials: M
authors.lastname: Staufenbiel
authors.forename: Rena
authors.initials: R
authors.lastname: Li
authors.forename: Yong
authors.initials: Y
authors.lastname: Shen
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy*; D000682:Amyloid / Q000378:metabolism*; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism; D002491:Central Nervous System Agents / Q000627:therapeutic use; D004338:Drug Combinations; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D010450:Endopeptidases / Q000378:metabolism; D036145:Ginsenosides / Q000627:therapeutic use*; D006801:Humans; D039823:Iridoids / Q000627:therapeutic use*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation; D053764:Presenilin-1 / Q000378:metabolism; D020521:Stroke / Q000517:prevention & control
chemical_list: D000682:Amyloid; D016564:Amyloid beta-Protein Precursor; D002491:Central Nervous System Agents; D004338:Drug Combinations; D004365:Drugs, Chinese Herbal; D036145:Ginsenosides; D039823:Iridoids; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D053764:Presenilin-1; C413604:nicastrin protein; C528243:tongluo jiunao; C007835:geniposide; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; C555827:presenilin enhancer 2, mouse; D016282:Aspartic Acid Endopeptidases; C509282:Bace1 protein, mouse; C498194:Aph1a protein, mouse; C035054:ginsenoside Rg1