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Agrimonia pilosa Ledeb., Cinnamomum cassia Blume, and Lonicera japonica Thunb. protect against cognitive dysfunction and energy and glucose dysregulation by reducing neuroinflammation and hippocampal insulin resistance in β-amyloid-infused rats

Bibliographic

Year of Publication:
2017
Contact PI Name:
Sunmin Park
Contact PI Affiliation:
Department of Food and Nutrition, Obesity/Diabetes Center, Hoseo University, South Korea
Co-Authors:
Suna Kang, Da Sol Kim, Bo Rerum Moon
Primary Reference (PubMED ID):
Funding Source:
National Research Foundation of Korea (NRF)
Korean Ministry of Trade, Industry and Energy
Study Goal and Principal Findings:

The water extracts of Cinnamomum cassia Blume bark (CCB; Lauraceae), Lonicera japonica Thunb. flower (LJT; Caprifoliaceae), and Agrimonia pilosa Ledeb. leaves (APL; Rosaceae) prevented amyloid-β (25–35)-induced cell death in PC12 cells in preliminary studies. They evaluated whether longterm oral consumption of CCB, LJT, and APL improves cognitive dysfunction and glucose homeostasis in rats with experimentally induced AD-type dementia. Male rats received hippocampal CA1 infusions of amyloid-β (25–35, AD) or amyloid-β (35–25, nonplaque forming, normal-controls, Non-AD-CON), at a rate of 3.6 nmol/day for 14 days. AD rats were divided into four groups receiving either 2% lyophilized water extracts of CCB, LJT, or APL or 2% dextrin (AD-CON) in high-fat diets (43% energy as fat). Hippocampal amyloid-β deposition, tau phosphorylation, and expressions of tumor necrosis factor (TNF)-α and inducible nitric oxide synthase (iNOS) (neruoinflammation markers) were increased, and insulin signaling decreased in AD-CON. CCB, LJT, and APL all prevented hippocampal amyloid-β accumulation and enhanced hippocampal insulin signaling. CCB, LJT, and APL decreased TNF-α and iNOS in the hippocampus and especially APL exhibited the greatest decrease. AD-CON exhibited cognitive dysfunction in passive avoidance and water maze tests, whereas CCB, LJT, and APL protected against cognitive dysfunction, and APL was most effective and was similar to Non-AD-CON. AD-CON had less fat oxidation as an energy fuel, but it was reversed by CCB, LJT, and especially APL. APL-treated rats had less visceral fat than AD-CON rats. AD-CON rats exhibited impaired insulin sensitivity and increased insulin secretion during oral glucose tolerance test compared with Non-AD-CON, but CCB and APL prevented the impairment. These results supported that APL, LJT, and CCB effectively prevent the cognitive dysfunction and the impairment of energy and glucose homeostasis induced by amyloid-β deposition by reducing neuroinflammation and enhancing insulin signaling. APL exhibited the greatest effectiveness for improving cognitive function.

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Natural Product
Therapeutic Agent:
Lonicera japonica Thunb
Therapeutic Target:
Multi Target
Therapy Type:
Natural Product
Therapeutic Agent:
Agrimonia pilosa Ledeb
Therapeutic Target:
Multi Target
Therapy Type:
Natural Product
Therapeutic Agent:
Cinnamomum cassia Blume
Therapeutic Target:
Multi Target

Animal Model

Model Information:
Species:
Rat
Model Type:
beta Amyloid Peptide Injection
Strain/Genetic Background:
Not Applicable

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
Passive Avoidance Test
Morris Water Maze
Motor Function
Locomotor Activity
Biochemical
Glucose Tolerance Test
Serum-Insulin
Insulin Tolerance Test
Blood-Glucose Level
Tumor Necrosis Factor alpha (TNF alpha)
Protein Kinase B (Akt/PKB)
Glycogen Synthase Kinase 3 beta (GSK3 beta)
phospho-Tau
Inducible Nitric Oxide Synthase (iNOS/NOS2)
phospho-Protein Kinase B (phospho-Akt/PKB)
phospho-Glycogen Synthase Kinase 3 beta (phospho-GSK3 beta)
Total Tau Protein
Immunochemistry
Brain-beta Amyloid Deposits
Toxicology
Body Weight
Physiology
Indirect Calorimetry
Energy Metabolism