Lab Anim Res.  2016 Jun;32(2):105-115. 10.5625/lar.2016.32.2.105.

Beneficial effect of diosgenin as a stimulator of NGF on the brain with neuronal damage induced by Aβ-42 accumulation and neurotoxicant injection

Affiliations
  • 1Department of Biomaterials Science, College of Natural Resources and Life Science/Life and Industry Convergence Research Institute, Pusan National University, Miryang, Korea. dyhwang@pusan.ac.kr
  • 2Biologics Division, Ministry of Food and Drug Administration (MFDS), Cheongju, Korea. cjbae76@gmail.com

Abstract

To investigate the beneficial effects of diosgenin (DG) on the multiple types of brain damage induced by Aβ-42 peptides and neurotoxicants, alterations in the specific aspects of brain functions were measured in trimethyltin (TMT)-injected transgenic 2576 (TG) mice that had been pretreated with DG for 21 days. Multiple types of damage were successfully induced by Aβ-42 accumulation and TMT injection into the brains of TG mice. However, DG treatment significantly reduced the number of Aβ-stained plaques and dead cells in the granule cells layer of the dentate gyrus. Significant suppression of acetylcholinesterase (AChE) activity and Bax/Bcl-2 expression was also observed in the DG treated TG mice (TG+DG group) when compared with those of the vehicle (VC) treated TG mice (TG+VC group). Additionally, the concentration of nerve growth factor (NGF) was dramatically enhanced in TG+DG group, although it was lower in the TG+VC group than the non-transgenic (nTG) group. Furthermore, the decreased phosphorylation of downstream members in the TrkA high affinity receptor signaling pathway in the TG+VC group was significantly recovered in the TG+DG group. A similar pattern was observed in p75NTR expression and JNK phosphorylation in the NGF low affinity receptor signaling pathway. Moreover, superoxide dismutase (SOD) activity was enhanced in the TG+DG group, while the level of malondialdehyde (MDA), a marker of lipid peroxidation, was lower in the TG+DG group than the TG+VC group. These results suggest that DG could exert a wide range of beneficial activities for multiple types of brain damage through stimulation of NGF biosynthesis.

Keyword

Diosgenin; neurodegenerative disorder; Aβ-42; trimethyltin; acetylcholinesterase; nerve growth factor

MeSH Terms

Acetylcholinesterase
Animals
Brain*
Dentate Gyrus
Diosgenin*
Lipid Peroxidation
Malondialdehyde
Mice
Nerve Growth Factor*
Neurodegenerative Diseases
Neurons*
Peptides
Phosphorylation
Superoxide Dismutase
Acetylcholinesterase
Diosgenin
Malondialdehyde
Nerve Growth Factor
Peptides
Superoxide Dismutase
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