A modified formulation of Chinese traditional medicine improves memory impairment and reduces Aβ level in the Tg-APPswe/PS1dE9 mouse model of Alzheimer's disease

J Ethnopharmacol. 2011 Sep 1;137(1):783-9. doi: 10.1016/j.jep.2011.06.046. Epub 2011 Jul 5.

Abstract

Ethnopharmacological relevance: SuHeXiang Wan (SHXW), a Chinese traditional medicine has been used orally for the treatment of seizures, infantile convulsion, stroke and so forth. Previously, we reported the effects of modified SHXW essential oil mixture of the fragrance containing herbs on the sedative effect, anticonvulsant property and antioxidative activity after fragrance inhalation.

Materials and methods: This study was undertaken to evaluate beneficial effects of a modified recipe of SHXW (termed as KSOP1009) consisting of a ethanol extract of 8 herbs including resin of Liquidambar orientalis Miller, seed of Myristica fragrans Houtt., rhizome of Cnidium officinale Makino, lumber of Santalum album L., fructus of Piper longum L., flower buds of Eugenia caryophyllata Merrill et Perry, pollen of Typha orientalis Presl., and root of Salvia miltiorrhiza Bunge in the neurodegenerative diseases such as Alzheimer's disease (AD). The transgenic mice of AD, Tg-APPswe/PS1dE9, were fed KSOP1009 or as a positive control, donepezil for 3 months from 4.5 months of age. Behavioral, immunological and ELISA analyses were used to assess memory impairment, Aβ accumulation and plaque deposition in the brain. Other in vitro works were performed to examine whether KSOP1009 inhibits the Aβ(1-42)-induced neurotoxicity in human neuroblastoma cell line, SH-SY5Y cells.

Results: Intake of KSOP1009 improved the Aβ-induced memory impairment and suppressed Aβ levels and plaque deposition in the brain of Tg-APPswe/PS1dE9 mice as much as that of donepezil treatment. KSOP1009 prevented the down-regulation of phospho-CREB and increased AKT phosphorylation in the AD-like brains. Moreover, KSOP1009 suppresses Aβ-induced apoptosis and ROS production in SH-SY5Y cells.

Conclusion: The present study suggests that KSOP1009 may develop as a therapeutic drug for treatment of AD patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / genetics
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Alzheimer Disease / psychology
  • Amyloid beta-Peptides / metabolism
  • Amyloid beta-Protein Precursor / genetics*
  • Amyloid beta-Protein Precursor / metabolism
  • Animals
  • Apoptosis / drug effects
  • Behavior, Animal / drug effects
  • Brain / drug effects*
  • Brain / metabolism
  • Brain / pathology
  • Cell Line, Tumor
  • Chemistry, Pharmaceutical
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • Disease Models, Animal
  • Donepezil
  • Dose-Response Relationship, Drug
  • Drugs, Chinese Herbal / chemistry
  • Drugs, Chinese Herbal / pharmacology*
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Indans / pharmacology
  • Memory / drug effects*
  • Memory Disorders / drug therapy*
  • Memory Disorders / genetics
  • Memory Disorders / metabolism
  • Memory Disorders / pathology
  • Memory Disorders / psychology
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Mutation*
  • Nootropic Agents / chemistry
  • Nootropic Agents / pharmacology*
  • Peptide Fragments / metabolism
  • Phosphorylation
  • Piperidines / pharmacology
  • Presenilin-1 / genetics*
  • Presenilin-1 / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Reactive Oxygen Species / metabolism
  • Time Factors

Substances

  • APP protein, human
  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • Creb1 protein, mouse
  • Cyclic AMP Response Element-Binding Protein
  • Drugs, Chinese Herbal
  • Indans
  • Nootropic Agents
  • PSEN1 protein, human
  • Peptide Fragments
  • Piperidines
  • Presenilin-1
  • Reactive Oxygen Species
  • SuHeXiang Wan
  • amyloid beta-protein (1-42)
  • Donepezil
  • Proto-Oncogene Proteins c-akt