A Standardized Extract of Asparagus officinalis Stem (ETAS(®)) Ameliorates Cognitive Impairment, Inhibits Amyloid β Deposition via BACE-1 and Normalizes Circadian Rhythm Signaling via MT1 and MT2

The prevalence of cognitive impairments and circadian disturbances increases in the elderly and Alzheimer’s disease (AD) patients. This study investigated the effects of a standardized extract of Asparagus officinalis stem, ETAS(®) on cognitive impairments and circadian rhythm status in senescence-accelerated mice prone 8 (SAMP8). ETAS(®) consists of two major bioactive constituents: 5-hydroxymethyl-2-furfural (HMF), an abundant constituent, and (S)-asfural, a novel constituent, which is a derivative of HMF. Three-month-old SAMP8 male mice were divided into a control, 200 and 1000 mg/kg BW ETAS(®) groups, while senescence-accelerated resistant mice (SAMR1) were used as the normal control. After 12-week feeding, ETAS(®) significantly enhanced cognitive performance by an active avoidance test, inhibited the expressions of amyloid-beta precursor protein (APP) and BACE-1 and lowered the accumulation of amyloid β (Aβ) in the brain. ETAS(®) also significantly increased neuron number in the suprachiasmatic nucleus (SCN) and normalized the expressions of the melatonin receptor 1 (MT1) and melatonin receptor 2 (MT2). In conclusion, ETAS(®) enhances the cognitive ability, inhibits Aβ deposition and normalizes circadian rhythm signaling, suggesting it is beneficial for preventing cognitive impairments and circadian rhythm disturbances in aging.