title: Genistein suppresses the mitochondrial apoptotic pathway in hippocampal neurons in rats with Alzheimer's disease.
abstract: Genistein is effective against amyloid-β toxicity, but the underlying mechanisms are unclear. We hypothesized that genistein may protect neurons by inhibiting the mitochondrial apoptotic pathway, and thereby play a role in the prevention of Alzheimer's disease. A rat model of Alzheimer's disease was established by intraperitoneal injection of D-galactose and intracerebral injection of amyloid-β peptide (25-35). In the genistein treatment groups, a 7-day pretreatment with genistein (10, 30, 90 mg/kg) was given prior to establishing Alzheimer's disease model, for 49 consecutive days. Terminal deoxyribonucleotidyl transferase-mediated dUTP nick end labeling assay demonstrated a reduction in apoptosis in the hippocampus of rats treated with genistein. Western blot analysis showed that expression levels of capase-3, Bax and cytochrome c were decreased compared with the model group. Furthermore, immunohistochemical staining revealed reductions in cytochrome c and Bax immunoreactivity in these rats. Morris water maze revealed a substantial shortening of escape latency by genistein in Alzheimer's disease rats. These findings suggest that genistein decreases neuronal loss in the hippocampus, and improves learning and memory ability. The neuroprotective effects of genistein are associated with the inhibition of the mitochondrial apoptotic pathway, as shown by its ability to reduce levels of caspase-3, Bax and cytochrome c.
authors.affiliation: School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, Anhui Province, China; Institute of Integrated Chinese and Western Medicine, Anhui Academy of Chinese Medicine, Hefei, Anhui Province, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, Anhui Province, China; Institute of Integrated Chinese and Western Medicine, Anhui Academy of Chinese Medicine, Hefei, Anhui Province, China.
authors.forename: Biao
authors.identifier: 0000-0002-3375-0073
authors.initials: B
authors.lastname: Cai
authors.affiliation: School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, Anhui Province, China; Institute of Integrated Chinese and Western Medicine, Anhui Academy of Chinese Medicine, Hefei, Anhui Province, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Shao
authors.affiliation: School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, Anhui Province, China; Institute of Integrated Chinese and Western Medicine, Anhui Academy of Chinese Medicine, Hefei, Anhui Province, China.
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Wang
authors.affiliation: School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, Anhui Province, China.
authors.forename: Run-Ze
authors.initials: RZ
authors.lastname: Cai
authors.affiliation: School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, Anhui Province, China.
authors.forename: Chang-Ju
authors.initials: CJ
authors.lastname: Ma
authors.affiliation: School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, Anhui Province, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Han
authors.affiliation: School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, Anhui Province, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Du
keywords: Alzheimer's disease; Bax; apoptosis; caspase-3; cytochrome c; genistein; hippocampus; learning; memory; mitochondrion; nerve regeneration; neural regeneration