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


BIBLIOGRAPHIC THERAPEUTIC AGENT ANIMAL MODEL EXPERIMENTAL DESIGN OUTCOMES

Bibliographic

Year of Publication:
2011
Contact PI Name:
Byung-Soo Koo
Contact PI Affiliation:
Department of Neuropsychiatry, Dongguk University International Hospital, Gyeonggi-do, Republic of Korea
Co-Authors:
Songhee Jeon, Shambhunath Bose, Jinyoung Hur, Kiyoung Jun, Young-Kyoon Kim, Kyoung Sang Cho
Primary Reference (PubMED ID):
Funding Source:
Oriental Medicine R&D Project
Korean Ministry of Health and Welfare and Family Affairs
Study Goal and Principal Findings:

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 Aβ1–42-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.

Bibliographic Notes:
Songhee Jeon (Dongguk University Research Institute of Biotechnology, Seoul, Republic of Korea) and Byung-Soo Koo (Department of Neuropsychiatry, Dongguk University International Hospital, Gyeonggi-do, Republic of Korea) are corresponding authors on this paper.

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Natural Product
Therapeutic Agent:
KSOP1009
Therapeutic Target:
Multi Target
Therapy Type:
Small Molecule
Therapeutic Agent:
Donepezil
Therapeutic Target:
Acetylcholinesterase

Animal Model

Model Information:
Species:
Mouse
Model Type:
APPxPS1
Strain/Genetic Background:
C57BL/6 x C3HF1

Experimental Design

Is the following information reported in the study?:
Power/Sample Size Calculation
Randomized into Groups
Blinded for Treatment
Blinded for Outcome Measures
Pharmacokinetic Measures
Pharmacodynamic Measures
Toxicology Measures
ADME Measures
Biomarkers
Dose
Formulation
Route of Delivery
Duration of Treatment
Frequency of Administration
Age of Animal at the Beginning of Treatment
Age of Animal at the End of Treatment
Sex as a Biological Variable
Study Balanced for Sex as a Biological Variable
Number of Premature Deaths
Number of Excluded Animals
Statistical Plan
Genetic Background
Inclusion/Exclusion Criteria Included
Conflict of Interest

Outcomes

Outcome Measured
Outcome Parameters
Behavioral
Morris Water Maze
Step-Through Passive Avoidance Test
Histopathology
beta Amyloid Deposits
beta Amyloid Load
Biochemical
Brain-Guanidine Soluble beta Amyloid Peptide 40
Brain-Guanidine Soluble beta Amyloid Peptide 42
Protein Kinase B (Akt/PKB)
phospho-Protein Kinase B (phospho-Akt/PKB)
cAMP Response Element-Binding Protein (CREB)
phospho-cAMP Response Element-Binding Protein (phospho-CREB)
Mitogen Activated Protein Kinase (MAPK)
phospho-Mitogen Activated Protein Kinase (phospho-MAPK)
Immunochemistry
Brain-beta Amyloid Deposits
Cell Biology
Cell Viability
Intracellular Reactive Oxygen Species
Toxicology
Body Weight
Food Intake

Source URL: http://alzped.nia.nih.gov/modified-formulation-chinese