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

Laboratory Animal Research volume 32, pages 105–115 (2016)Cite this article

Abstract

To investigate the beneficial effects of diosgenin (DC) 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 DC for 21 days. Multiple types of damage were successfully induced by Aß-42 accumulation and TMT injection into the brains of TG mice. However, DC treatment significantly reduced the number of Aß-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 DC 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 DC could exert a wide range of beneficial activities for multiple types of brain damage through stimulation of NGF biosynthesis.

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  1. This author is equally contributed to this study.

Authors and Affiliations

  1. Department of Biomaterials Science, College of Natural Resources and Life Science, Pusan National University, 50 Cheonghak-ri, Samnangjin-eup, Miryang, Gyeongnam, 50463, Korea

    Eun-Kyoung Koh, Woo-Bin Yun, Ji-Eun Kim, Sung-Hwa Song, Ji-Eun Sung, Hyun-Ah Lee, Eun-Ji Seo & Dae-Youn Hwang

  2. Biologics Division, Ministry of Food and Drug Administration (MFDS), Cheongju, Korea

    Seung-Wan Jee & Chang-Joon Bae

  3. Department of Biopharmaceuticals and Herbal Medicine Evaluation Department, National Institute of Food and Drug Safety Evaluation, Korea FDA 187 Osongsaengmyeong2(i)ro, Osong-eup, Heungdeok-gu, cheongju, Chungbuk, 28159, Korea

    Chang-Joon Bae

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  1. Eun-Kyoung Koh
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Correspondence to Chang-Joon Bae or Dae-Youn Hwang.

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Koh, EK., Yun, WB., Kim, JE. et al. Beneficial effect of diosgenin as a stimulator of NGF on the brain with neuronal damage induced by Aβ-42 accumulation and neurotoxicant injection. Lab Anim Res 32, 105–115 (2016). https://doi.org/10.5625/lar.2016.32.2.105

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  • DOI: https://doi.org/10.5625/lar.2016.32.2.105

Keywords

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

Laboratory Animal Research

ISSN: 2233-7660