Effects of Curculigoside on Memory Impairment and Bone Loss via Anti-Oxidative Character in APP/PS1 Mutated Transgenic Mice

PLoS One. 2015 Jul 17;10(7):e0133289. doi: 10.1371/journal.pone.0133289. eCollection 2015.

Abstract

Alzheimer's disease (AD) and osteoporosis are two closely related multifactorial progressively degenerative diseases that predominantly affect aged people. These two diseases share many common risk factors, including old age, being female, smoking, excessive drinking, low estrogen, and vitamin D3 levels. Additionally, oxidative damage and the dysfunction of the antioxidant system play important roles in the pathogenesis of osteoporosis and AD. Aβ not only leads to impaired memory but also plays a crucial role in the demineralization process of bone tissues of older people and women with menopause. Curculigoside can promote calcium deposition and increase the levels of ALP and Runx2 in osteoblasts under oxidative stress via anti-oxidative character. Therefore, we investigated the effects of CUR on the spatial learning and memory by the Morris water maze and brain immunohistochemistry, and bone microstructure and material properties of femurs by micro-computed tomography and mechanical testing in APP/PS1 mutated transgenic mice. Oral administration of CUR can significantly enhance learning performance and ameliorate bone loss in APP/PS1 mutated transgenic mice, and the mechanism may be related to its antioxidant effect. Based on these results, CUR has real potential as a new natural resource for developing medicines or dietary supplements for the prevention and treatment of the two closely linked multifactorial progressive degenerative disorders, AD and osteoporosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acid Phosphatase / blood
  • Amyloid beta-Protein Precursor / genetics
  • Animals
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use*
  • Benzoates / pharmacology
  • Benzoates / therapeutic use*
  • Biomechanical Phenomena / drug effects
  • Bone Density / drug effects
  • Bone Resorption / blood
  • Bone Resorption / complications*
  • Bone Resorption / drug therapy*
  • Bone Resorption / physiopathology
  • Brain / drug effects
  • Brain / metabolism
  • Brain / physiopathology
  • Femur / drug effects
  • Femur / metabolism
  • Femur / physiopathology
  • Glucosides / pharmacology
  • Glucosides / therapeutic use*
  • Interleukin-6 / blood
  • Isoenzymes / blood
  • Memory Disorders / blood
  • Memory Disorders / complications*
  • Memory Disorders / drug therapy*
  • Memory Disorders / physiopathology
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Mutation / genetics*
  • Presenilin-1 / genetics
  • Spatial Memory / drug effects
  • Tartrate-Resistant Acid Phosphatase
  • Tumor Necrosis Factor-alpha / blood

Substances

  • Amyloid beta-Protein Precursor
  • Antioxidants
  • Benzoates
  • Glucosides
  • Interleukin-6
  • Isoenzymes
  • Presenilin-1
  • Tumor Necrosis Factor-alpha
  • curculigoside
  • Acid Phosphatase
  • Tartrate-Resistant Acid Phosphatase

Grants and funding

This study was supported by the grants from the National Natural Science Foundation of China (Grant No. 81274152), the natural science foundation of Shanghai science and Technology Commission, China (Grant No. 13ZR1449600), and the scientific research fund of Shanghai City Health Planning Commission, China (Grant No. 2013299).