α-Pinene is a major monoterpene of the pine tree essential oils. It has been reported that α-pinene shows anxiolytic and hypnotic effects upon inhaled administration. However, hypnotic effect by oral supplementation and the molecular mechanism of α-pinene have not been determined yet. By combining in vivo sleep behavior, ex vivo electrophysiological recording from brain slices, and in silico molecular modeling, we demonstrate that (-)-α-pinene shows sleep enhancing property through a direct binding to GABA-benzodiazepine (BZD) receptors by acting as a partial modulator at the BZD binding site. The effect of (-)-α-pinene on sleep-wake profiles was evaluated by recording electroencephalogram and electromyogram. The molecular mechanism of (-)-α-pinene was investigated by electrophysiology and molecular docking study. (-)-α-pinene significantly increased the duration of non-rapid eye movement sleep (NREMS) and reduced the sleep latency by oral administration without affecting duration of rapid eye movement sleep and delta activity. (-)-α-pinene potentiated the GABA receptor-mediated synaptic response by increasing the decay time constant of sIPSCs in hippocampal CA1 pyramidal neurons. These effects of (-)-α-pinene on sleep and inhibitory synaptic response were mimicked by zolpidem, acting as a modulator for GABA-BZD receptors, and fully antagonized by flumazenil, an antagonist for GABA-BZD receptor. (-)-α-pinene was found to bind to aromatic residues of α1- and -γ2 subunits of GABA-BZD receptors in the molecular model. We conclude that (-)-α-pinene enhances the quantity of NREMS without affecting the intensity of NREMS by prolonging GABAergic synaptic transmission, acting as a partial modulator of GABA-BZD receptors and directly binding to the BZD binding site of GABA receptor.

Curcumin is a well-known component of traditional turmeric (Curcuma longa), which has been reported to prevent obesity and diabetes. However, the effect of curcumin on hepatic lipid metabolism remains unclear. The aim of this study was to examine the effects of curcumin on hepatic steatosis in high-fat/cholesterol diet (HFD)-induced obese mice. Male C57BL/6J mice were fed a normal diet (ND), HFD or HFD with 0.15% curcumin (HFD+C) for 11 weeks. We found that curcumin significantly lowered the body-weight and adipose tissue weight of mice in the HFD+C group compared with the findings for the HFD group (p < 0.05). The levels of total cholesterol, fasting glucose and insulin in serum were decreased, and HFD-induced impairment of insulin sensitivity was improved by curcumin supplementation (p < 0.05). Curcumin protected against the development of hepatic steatosis by reducing hepatic fat accumulation. Moreover, curcumin activated AMP-activated protein kinase (AMPK) and elevated the gene expression of peroxisome proliferator-activated receptor alpha. By contrast, curcumin suppressed the HFDmediated increases in sterol regulatory element-binding protein-1, acetyl-CoA carboxylase 1, fatty acid synthase and cluster of differentiation 36 expression. Taken together, these findings indicate that curcumin attenuates HFD-induced hepatic steatosis by regulating hepatic lipid metabolism via AMPK activation, suggesting its use as a therapeutic for hepatic steatosis.

No abstract

Amyloid beta protein (Abeta) may be involved in the progression of Alzheimer's disease (AD), by acting as a neurotoxin and eliciting oxidative stress. This study was designed to determine the effects of Glycyrrhiza uralensis Fisch. water extract (GWE) on the cognitive deficits and oxidative stress induced by the administration of Abeta(25-35) in mice. Mice in two of the four animal groups were fed an experimental diet containing either 0.5 or 1% GWE for the entire 6-week experimental period. Control mice and a further experimental group were fed a non-GWE diet. Abeta(25-35) was administered to the three experimental groups by intracerebroventricular (i.c.v.) injection (10 microg/10 microl/mouse) once per week in weeks 5 and 6 of the experimental period. Behavioral changes were assessed using both a passive avoidance (after the injection of Abeta(25-35) in week 5) and the Morris water-maze tests (after the injection of Abeta(25-35) in week 6). Control animals were administered vehicle alone. The prolonged consumption of a diet containing GWE ameliorated the cognitive deficits caused by the i.c.v. injections of Abeta(25-35). Treatment with Abeta(25-35) led to higher concentrations of thiobarbituric acid reactive substances in the brain, and GWE attenuated this response. There was a decrease in catalase activity in the group provided with 1% GWE. Acetylcholinesterase activity was significantly reduced in the brains of all GWE-treated animals compared to that in the non-GWE-fed experimental group. These results suggest that GWE exerts a protective effect against the cognitive impairments often observed in AD, and that in mice this effect is mediated by antioxidant actions against oxidative stress.

The present study aimed to extract total phenolic compounds (TPC), total flavonoid compounds (TFC), and ascorbic acid (AA) from the fruit of rugosa rose ( Thunb.) by ultrasound-assisted extraction (UAE), and to evaluate their antioxidant activities. UAE significantly increased the extract yield compared with that obtained using the conventional method. TPC, TFC, and AA were extracted, depending on the extraction conditions (temperature, time, and ethanol concentration), in the range of 50.73-96.69, 15.93-31.88, and 3.06-6.08 mg/g, respectively. TPC and TFC were effectively extracted at a relatively high temperature (50 °C) than AA was (30 °C). The solvent condition used to extract TPC, TFC, and AA was 50% ethanol. The UAE condition for the highest antioxidant activity was obtained 30 °C, 30 min, and 50% ethanol, which were the same condition for the highest AA extraction. Among the extracts, AA showed a strong correlation with antioxidant activity at -value of 0.001.

No abstract

Our previous study demonstrated that phlorotannin supplement had a sleep-promoting effect in rodents. In the present study, we investigated whether the phlorotannin supplement could improve sleep in subjects with self-reported sleep disturbances. In a randomized, double-blind, placebo-controlled trial, 24 subjects consumed either a placebo or phlorotannin supplement (500 mg/day) for 1 week, 30-60 min prior to bedtime. Sleep parameters were assessed at baseline and at 1 week with sleep questionnaires and polysomnography. At the end of the treatment period, the complete sets of sleep parameters from 20 subjects. Phlorotannin resulted in a significant increase in "Sleep duration" scores compared to the placebo (p = .044), although there were no significant differences on the total PSQI scores. Polysomnography revealed that wakefulness after sleep onset was significantly lower in the phlorotannin group compared to the placebo group (phlorotannin vs. placebo, -25.5 ± 30.5 vs. -1.7 ± 14.9; p = .045) as well as total wake time (phlorotannin vs. placebo, -0.9 ± 3.0 vs. -6.1 ± 6.8; p = .048). Additionally, the respiratory disturbance index during supine rapid eye movement sleep was significantly lower in the phlorotannin group (p = .035). There were no serious adverse effects in either group. Our data suggest that the phlorotannin supplement improved sleep maintenance (WHO ICTRP: KCT0001892).

Anthricin (deoxypodophyllotoxin) is a natural product isolated from Anthriscus sylvestris (L.) Hoffm. (Apiaceae). Here, we investigated the effect of anthricin on autophagy and mammalian target of rapamycin (mTOR) signaling as anticancer actions in breast cancer cells. Many studies have supported the contention that the phosphoinositide 3-kinase (PI3K)/Akt/mTORC1 pathway is considerably deregulated in breast cancer and that autophagy plays important roles in the development of this type of cancer, although the exact underlying mechanisms remain unknown. Our data confirmed that anthricin markedly induced apoptosis in 2 breast cancer cell lines, MCF7 (estrogen receptor positive) and MDA-MB-231 (estrogen receptor, progesterone receptor, and Her2/Neu receptor negative). Anthricin treatment decreased the levels of phosphorylated Akt and mTORC1, followed by inhibition of cell growth. Interestingly, blockage of autophagy by a pharmacological inhibitor or genetic deletion of ULK1 and Atg13 accelerated anthricin-induced apoptosis, suggesting that autophagy has cytoprotective effects. Taken together, our results indicate that anthricin is an inhibitor of mTOR and that a combination of an autophagy inhibitor and anthricin may serve as a new promising strategy for the treatment of breast cancer cells.