Effects of Trigonella foenum-graecum seeds extract on Alzheimer's disease transgenic model mouse and its potential active compound transferred to the brain

Trigonella foenum-graecum seeds (TF) (Fabaceae) is a well-known plant traditionally used as food and medicinal herb. A variety of pharmacological effects of TF extract were shown against diabetic, cancer and dementia in animal models. Concerning anti-dementia effects of TF extract, it has not been evaluated in Alzheimer’s disease models. In addition, those previous studies, active constituents in TF extract for memory function were not identified. We aimed to clarify effects of 30% ethanol TF extract on Alzheimer’s disease model, 5XFAD mouse, and determine a major active compound in the brain after oral intake of TF extract. Trigonelline content in TF extract and trigonelline penetration in the brain after oral administration of TF extract (5000 mg/kg, once) were quantified by LCMS/ MS analysis. Memory recovery by TF extract (100, 500 mg/kg/day for 17 days) was evaluated by object location memory test. Expression level of neurofilament light in the cerebral cortex was quantified by western blotting. Trigonelline was detected in the cerebral cortex of 5XFAD mice 24 h after oral administration of TF extract. Oral administration of TF extract (500 mg/kg/day) for 17 days improved object location memory. TF extract increased dose-dependently the level of axonal protein, neurofilament light in 5XFAD mice. These results suggest that TF extract could be an expected therapeutic candidate for Alzheimer’s disease, and supposed one of active compounds transferred in the brain is trigonelline. This study is the first report to determine trigonelline penetration in the brain after oral administration of TF extract.