title: Beneficial effect of diosgenin as a stimulator of NGF on the brain with neuronal damage induced by Aβ-42 accumulation and neurotoxicant injection.
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 p75(NTR) 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.
authors.affiliation: Department of Biomaterials Science, College of Natural Resources and Life Science/Life and Industry Convergence Research Institute, Pusan National University, Miryang, Korea.
authors.forename: Eun-Kyoung
authors.initials: EK
authors.lastname: Koh
authors.affiliation: Department of Biomaterials Science, College of Natural Resources and Life Science/Life and Industry Convergence Research Institute, Pusan National University, Miryang, Korea.
authors.forename: Woo-Bin
authors.initials: WB
authors.lastname: Yun
authors.affiliation: Department of Biomaterials Science, College of Natural Resources and Life Science/Life and Industry Convergence Research Institute, Pusan National University, Miryang, Korea.
authors.forename: Ji-Eun
authors.initials: JE
authors.lastname: Kim
authors.affiliation: Department of Biomaterials Science, College of Natural Resources and Life Science/Life and Industry Convergence Research Institute, Pusan National University, Miryang, Korea.
authors.forename: Sung-Hwa
authors.initials: SH
authors.lastname: Song
authors.affiliation: Department of Biomaterials Science, College of Natural Resources and Life Science/Life and Industry Convergence Research Institute, Pusan National University, Miryang, Korea.
authors.forename: Ji-Eun
authors.initials: JE
authors.lastname: Sung
authors.affiliation: Department of Biomaterials Science, College of Natural Resources and Life Science/Life and Industry Convergence Research Institute, Pusan National University, Miryang, Korea.
authors.forename: Hyun-Ah
authors.initials: HA
authors.lastname: Lee
authors.affiliation: Department of Biomaterials Science, College of Natural Resources and Life Science/Life and Industry Convergence Research Institute, Pusan National University, Miryang, Korea.
authors.forename: Eun-Ji
authors.initials: EJ
authors.lastname: Seo
authors.affiliation: Biologics Division, Ministry of Food and Drug Administration (MFDS), Cheongju, Korea.
authors.forename: Seung-Wan
authors.initials: SW
authors.lastname: Jee
authors.affiliation: Biologics Division, Ministry of Food and Drug Administration (MFDS), Cheongju, Korea.
authors.forename: Chang-Joon
authors.initials: CJ
authors.lastname: Bae
authors.affiliation: Department of Biomaterials Science, College of Natural Resources and Life Science/Life and Industry Convergence Research Institute, Pusan National University, Miryang, Korea.
authors.forename: Dae-Youn
authors.initials: DY
authors.lastname: Hwang
keywords: Aβ-42; Diosgenin; acetylcholinesterase; nerve growth factor; neurodegenerative disorder; trimethyltin