Analysis of the Effects of Known Sleep-Support Supplements in Relation to Life Habits, Sleep Conditions, and Sleep Problems.

Sleep is a crucial component of health, and insomnia is among the most common and vexing of life-habit-related disorders. While dietary sleep-support supplements can improve sleep, choosing an effective dietary supplement can be challenging for users due to the wide variety of options available and the varying effects experienced by different individuals. In this study, to identify new criteria for estimating the effects of dietary supplements, we examined the relationships among the dietary supplements, the pre-conditions (PCs; defined as the life habits and sleep conditions before supplementation), and the sleep problems of subjects before supplementation. An open, randomized, cross-over intervention trial enrolling 160 subjects was conducted to test the efficacy of each dietary supplement (Analysis 1) and the relationships among dietary supplements, the PCs, and sleep problems (Analysis 2). To this end, l-theanine (200 mg/day), γ-aminobutyric acid (GABA) (111.1 mg/day), Apocynum venetum leaf extract (AVLE) (50 mg/day), and l-serine (300 mg/day) were administered to subjects. Before the first intervention period, life habits and sleep conditions were surveyed to identify each subject's PCs. For each combination of supplements and sleep problems, PCs were compared between subjects whose sleep problems were improved and subjects whose sleep problems were not improved via supplementation. All the tested supplements were found to ameliorate sleep problems significantly (Analysis 1). In Analysis 2, the PCs specific to improved subjects were found to differ depending on the dietary supplements and sleep problems. In addition, subjects who consumed dairy products often showed improvement in their sleep problems with all the tested supplements. This study suggests the possibility of personalizing sleep-support supplementation based on personal life habits, sleep conditions, and sleep problems, in addition to the known efficacy of dietary supplements.

Central and Enteric Neuroprotective Effects by Eucommia ulmoides Extracts on Neurodegeneration in Rotenone-induced Parkinsonian Mouse.

Parkinson's disease (PD) is a progressive neurodegenerative disease of both the central and peripheral / enteric nervous systems. Oxidative stress and neuroinflammation are associated with the pathogenesis of PD, suggesting that anti-oxidative and anti-inflammatory compounds could be neuroprotective agents for PD. Eucommia ulmoides (EU) is a traditional herbal medicine which exerts neuroprotective effects by anti-inflammatory and anti-oxidative properties. Our previous study showed that treatment with chlorogenic acid, a component of EU, protected against neurodegeneration in the central and enteric nervous systems in a PD model. In this study, we examined the effects of EU extract (EUE) administration on dopaminergic neurodegeneration, glial response and α-synuclein expression in the substantia nigra pars compacta (SNpc), and intestinal enteric neurodegeneration in low-dose rotenone-induced PD model mice. Daily oral administration of EUE ameliorated dopaminergic neurodegeneration and α-synuclein accumulation in the SNpc. EUE treatment inhibited rotenone-induced decreases in the number of total astrocytes and in those expressing the antioxidant molecule metallothionein. EUE also prevented rotenone-induced microglial activation. Furthermore, EUE treatment exerted protective effects against intestinal neuronal loss in the PD model. These results suggest that EU exerts neuroprotective effects in the central and enteric nervous systems of rotenone-induced parkinsonism mice, in part by glial modification.

Chronic Systemic Exposure to Low-Dose Rotenone Induced Central and Peripheral Neuropathology and Motor Deficits in Mice: Reproducible Animal Model of Parkinson's Disease.

Epidemiological studies demonstrated that pesticide exposure, such as rotenone and paraquat, increases the risk of Parkinson's disease (PD). Chronic systemic exposure to rotenone, a mitochondrial complex I inhibitor, could reproduce many features of PD. However, the adoption of the models is limiting because of variability in animal sensitivity and the inability of other investigators to consistently reproduce the PD neuropathology. In addition, most of rotenone models were produced in rats. Here, we tried to establish a high-reproducible rotenone model using C57BL/6J mice. The rotenone mouse model was produced by chronic systemic exposure to a low dose of rotenone (2.5 mg/kg/day) for 4 weeks by subcutaneous implantation of rotenone-filled osmotic mini pump. The rotenone-treated mice exhibited motor deficits assessed by open field, rotarod and cylinder test and gastrointestinal dysfunction. Rotenone treatment decreased the number of dopaminergic neuronal cells in the substantia nigra pars compacta (SNpc) and lesioned nerve terminal in the striatum. In addition, we observed significant reduction of cholinergic neurons in the dorsal motor nucleus of the vagus (DMV) and the intestinal myenteric plexus. Moreover, α-synuclein was accumulated in neuronal soma in the SNpc, DMV and intestinal myenteric plexus in rotenone-treated mice. These data suggest that the low-dose rotenone mouse model could reproduce behavioral and central and peripheral neurodegenerative features of PD and be a useful model for investigation of PD pathogenesis.