Effects of Chronic Administration of Green Tea Ethanol Extract on Sleep Architecture in Mice: A Comparative Study with a Representative Stimulant Caffeine.

Wakefulness is defined as a state in which individuals can react to a change in situations. The number of people staying awake and compensating for lack of sleep has increased in recent years. Caffeine, a representative stimulant, is the most extensively consumed compound globally and is mainly consumed through coffee. Although green tea (Camellia sinensis L.) contains high caffeine content like coffee, its arousal-inducing effects have not yet been studied. In the present study, we aimed to identify the arousal-inducing effect of GT during a chronic administration period (three weeks) using analysis of sleep architecture. Treatment with GT (1500 mg/kg) significantly elevated the sleep latency and wakefulness throughout the treatment period, and chronic administration of GT consistently maintained an increase in wakefulness for up to 3 h. During the treatment period, the arousal-inducing effect of GT (1500 mg/kg) occurred without any change in the tolerance phenomenon or withdrawal symptoms, similar to that observed with caffeine (25 mg/kg). GT (1500 mg/kg) containing 95.6 mg/kg of caffeine did not produce a better arousal-inducing effect than caffeine at 25 mg/kg. These results indicate that the arousal-inducing effect of GT persisted for three weeks without adverse effects and that GT can control the arousal-inducing effects of caffeine due to the hypnotic effects of its other constituents.

Effects of Green Kiwifruit Peel Extract on Sleep-Wake Profiles in Mice: A Polysomnographic Study Based on Electroencephalogram and Electromyogram Recordings.

In the previous study, it was reported that green kiwifruit peel ethanol extract (GKPEE) increases sleep duration and decreases sleep latency in pentobarbital-treated mice. The pentobarbital-induced sleep test can be used to verify sleep quantity, which includes factors such as sleep duration and latency, but not sleep quality. In the present study, the sleep-promoting effects of GKPEE were investigated by the analysis of electroencephalogram (EEG) and electromyogram in mice and were compared with the results of diazepam (DZP), a representative sedative-hypnotic agent. The acute administration of GKPEE (250, 500 and 1000 mg/kg) increased the amount of non-rapid eye movement sleep (NREMS) and decreased sleep latency in a dose-dependent manner. The effect of GKPEE at 1000 mg/kg produced persistently significantly different results until the second hour of time-course changes. In particular, GKPEE did not produce any change in delta activity compared to DZP. Furthermore, sub-chronic administration (15 days) of GKPEE (500 mg/kg) continued sleep-promoting effects, whilst the EEG power density of NREMS did not show significant differences, indicating that there were no tolerance phenomena. Our findings suggest that GKPEE may be a promising natural sleep aid for treating sleep disorders. In addition, considering the number of by-products discarded each year by the food industry, the application of GKPEE here contributes to the utilization of processed kiwifruit by-products and can help to solve environmental problems.

Curcuminoids, a major turmeric component, have a sleep-enhancing effect by targeting the histamine H1 receptor.

Turmeric (Curcuma longa) had been considered as a universal panacea in functional foods and traditional medicines. In recent, the sedative-hypnotic effect of turmeric extract (TE) was reported. However, sleep-promoting compounds in TE have been not yet demonstrated. Curcuminoids (curcumin, demethoxycurcumin, and bisdemethoxycurcumin) are the major constituents of turmeric being responsible for its various biological activities. Therefore, they can be first assumed to be sedative-hypnotic compounds of TE. In the present study, we aimed to investigate the effects and underlying mechanisms of curcuminoids and each constituent on the sleep-wake cycle of mice. Molecular docking studies, histamine H1 receptor (H1R) binding assays, and H1R knockout animal studies were used to investigate the molecular mechanisms underlying the sleep-promoting effects. Curcuminoids and their constituents reduced sleep latency and increased sleep duration in the pentobarbital-induced sleep test in mice. In addition, curcuminoids significantly increased the duration of NREMS and reduced sleep latency without altering the REMS and delta activity. Curcumin, demethoxycurcumin, and bisdemethoxycurcumin were predicted to interact with H1R in the molecular model. In the binding affinity assay, we found that curcuminoids, as well as their constituents, significantly bind to H1R with the Ki value of 1.49 µg mL-1. Furthermore, sleep latency was reduced and NREMS frequency was increased following curcuminoid administration in wild-type mice but not in H1R knockout mice. Therefore, we conclude that curcuminoids reduce sleep latency and enhance the quantity of NREMS by acting as modulators of H1R, indicating their usefulness in treating insomnia.

A Novel Potent Sleep-Promoting Effect of Turmeric: Turmeric Increases Non-Rapid Eye Movement Sleep in Mice Via Histamine H1Receptor Blockade.

SCOPE: Turmeric has a broad spectrum of biological properties; however, the sleep-promoting effects of turmeric have not yet been reported. Thus, this study aims to investigate the effect of turmeric on sleep and the molecular mechanism underlying this effect. METHODS AND RESULTS: Pentobarbital-induce sleep test and sleep-wake profile assessment using recorded electroencephalography are used to evaluate the hypnotic effects of the turmeric extract (TE) compared to diazepam on sleep in mice. Additionally, the molecular mechanism of TE's sleep effect is investigated using ex vivo electrophysiological recordings from brain slices in histamine H1 receptor (H1 R) knockout mice. Oral administration of TE and diazepam significantly reduce sleep latency and increase non-rapid eye movement sleep (NREMS) duration without delta activity in mice. Like doxepin, TE inhibits the H1 R agonist (2-pyridylethylamine dihydrochloride)-induced increase in action potentials in the hypothalamic neurons. In animal tests using neurotransmitter agonists or antagonists, TE effect mimick H1 R antagonistic effect of doxepin. Additionally, both reduce sleep latency and increase NREMS in wild-type mice, although these effects are not observed in H1 R knockout mice. CONCLUSION: TE has a sleep-promoting effect owing to reduction in sleep latency and enhancement of NREMS via H1 R blockade; therefore, it could be useful in insomnia.

Cassia tora Seed Improves Pancreatic Mitochondrial Function Leading to Recovery of Glucose Metabolism.

Mitochondrial metabolism plays a crucial role in insulin resistance and insulin secretion in type 2 diabetes mellitus (T2D). Some studies have focused on how Cassia tora extracts affect insulin resistance and hyperglycemia. However, the effects of Cassia tora extracts on mitochondrial dysfunction associated with insulin secretion have not been well explained. In this study, well-known effective compounds extracted from Cassia tora using 70% ethanol were administered to a high-fat diet (HFD) fed mouse to examine the effects of Cassia tora ethanolic extracts (CSEE) on mitochondrial dysfunction in the pancreas. Furthermore, we examined how CSEE regulates the basal mechanism of insulin secretion through mitochondrial functions. Our experimental data suggest that pancreatic mitochondrial metabolism in HFD mice is enhanced to compensate for constrained glucose consumption. HFD-fed mice treated with CSEE showed improved pancreatic mitochondrial functions resulting in alleviation of insulin resistance at target tissue as well as basal hyperinsulinemia.

Memory-enhancing effects of Ishige foliacea extract: In vitro and in vivo study.

Ishige foliacea is used as a functional food in East-Asian countries. We evaluated the memory-enhancing effect of an ethanol extract of I. foliacea (EEI) using in vitro and in vivo models. In vitro acetylcholinesterase and ß-secretase inhibitory activities, antioxidant properties, and neuroprotective effects against human neuronal cell death by H2 O2 and ß-amyloid (Aß) were investigated. We explored the memory-enhancing effect and its underlying mechanism in a mouse model of scopolamine (SCO)-induced memory deficits. EEI showed free radical scavenging and acetylcholinesterase and ß-secretase inhibition activities. Additionally, EEI significantly decreased neuronal cell death induced by H2 O2 or Aß in human neuroblastoma SH-SY5Y cells. In behavior tests, SCO-induced memory deficits was improved by EEI administration. EEI increased the protein expression of brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) and phosphorylated extracellular signal-regulated kinase, which are related to synaptic plasticity in the hippocampus. EEI may ameliorate memory deficits and prevent neurodegenerative disorders. PRACTICAL APPLICATIONS: As the population ages, dementia, a neurodegenerative disease, is becoming an important problem. Various Alzheimer's drugs have been developed based on the disease mechanism, but alternative treatments are required because of the low bioavailability and hepatotoxicity of current medications. Ishige foliacea is a type of brown algae containing various bioactive substances. Phlorotannins, known as brown algae polyphenols, have been studied for their various functionalities such as, anticancer, anti-obesity, antioxidant, and sleep improvement effects, and have attracted attention as raw materials for developing new natural products. We found that the EEI mitigates SCO-induced damage by protecting neurons from oxidative stress-induced cell damage, controlling synthesis mechanisms of the causative agents of AD, and activating BDNF-TrkB-ERK signaling to promote memory function in the hippocampus. The results of this study can serve as a foundation for further research. Additionally, I. foliacea may be useful for treating and improving AD.

Administration of Asian Herb Bennet (Geum japonicum) Extract Reverses Depressive-Like Behaviors in Mouse Model of Depression Induced by Corticosterone.

Geum japonicum, commonly known as Asian herb bennet, has been used as a diuretic, astringent, anti-dizziness, and anti-headache agent in traditional medicine. Since the antidepressant-like effects of G. japonicum extract have not been well studied, we examined the antidepressant-like effects of G. japonicum extract using depressive-like behavior induced in mice through daily injection of corticosterone (CORT). ICR mice (male, 8 weeks old) were treated with CORT (40 mg/kg, i.p.) and orally administered using oral gavage needles with G. japonicum extract (30, 100, and 300 mg/kg) for 4 weeks. Behavioral experiments were performed 1 h after administration. The control mice exhibited a significant increase in the immobility times in the tail suspension and forced swim tests as well as the step-through latency time in the passive avoidance test. Further, the control group showed a significant decrease in their sucrose consumption. However, treatment with G. japonicum extract at doses of 100 and 300 mg/kg significantly improved these depression-like behaviors without altering the locomotor activity. Moreover, treatment with G. japonicum extract significantly prevented the decrease in the expression of brain-derived neurotrophic factor (BDNF) in the hippocampus. In addition, G. japonicum extract had neuroprotective effects against CORT-induced neurotoxicity in SH-SY5Y cells. Our study indicates that G. japonicum extract exhibits antidepressant-like activity in CORT-induced depressive mice, which might be as a result of increased BDNF expression.

Rice bran extract supplement improves sleep efficiency and sleep onset in adults with sleep disturbance: A randomized, double-blind, placebo-controlled, polysomnographic study.

We previously reported that rice bran extract supplement (RBS) administration to mice decreased sleep latency and induced non-rapid eye movement (NREM) sleep via inhibition of the histamine H1 receptor. Based on this, we performed the first clinical trial to investigate whether RBS would be beneficial to subjects with disturbed sleep. We performed a randomized, double-blinded, placebo-controlled, 2-week study. Fifty subjects with sleep disturbance were enrolled and received either RBS (1,000 mg/day) or placebo. Polysomnography was performed, and Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale (ESS), and Fatigue Severity Scale were administered at the initiation and termination of the study. Compared with the placebo, RBS led to significant polysomnographic changes, including decreased sleep latency (adjusted, P = 0.047), increased total sleep time (P = 0.019), and improved sleep efficiency (P = 0.010). Additionally, the amount of stage 2 sleep significantly increased in the RBS group. When adjusted for caffeine intake, wakefulness after sleep onset, total wake time, and delta activity tended to decrease in the RBS group. RBS administration decreased ESS scores. There were no reported serious adverse events in both groups. RBS improved sleep in adults with sleep disturbance. Trial registration: WHO ICTRP, KCT0001893.

Standardized Citrus unshiu peel extract ameliorates dexamethasone-induced neurotoxicity and depressive-like behaviors in mice.

Dried Citrus unshiu peel, also known as Chinpi, have been commonly used as a traditional medicine to improve for allergy, inflammation and hepatopathy. Many previously studies have reported that citrus flavonoids show neuroprotective activities. However, the antidepressant-related effects of C. unshiu peels have not been well characterized. Here, the antidepressant-like effects of standardized C. unshiu peel extract (SCP) were evaluated in in vivo and in vitro depression models induced by dexamethasone (DEX), a synthetic glucocorticoid. Male ICR mice (9-week-old) were injected the DEX (40 mg/kg) and were orally given SCP daily (30, 100, and 300 mg/kg) for 14 consecutive days. The depressive-like behaviors were determined by use of open filed test (OFT), sucrose preference test (SPT), tail suspension test (TST), and forced swim test (FST). We show that treatment with SCP significantly alleviated DEX-induced depressive-like behaviors and reduced neurotoxicity in a concentration dependent manner in SH-SY5Y cells. Additionally, repeated DEX injection markedly decreased brain derived neurotrophic factor (BDNF) level, tropomyosin receptor kinase B (TrkB), and cyclic AMP-response element-binding protein (CREB), while SCP treatment improved these levels in the cerebral cortex and hippocampus regions. Our findings suggest that SCP exhibits significant antidepressant-like effects in the DEX-induced depressive animal model, and this activity may be mediated by preventing corticosterone-induced neurotoxicity.

Rice bran supplement prevents UVB-induced skin photoaging in vivo.

Although rice bran consumption is reportedly has numerous beneficial effects on human health, the relationship between rice bran and the prevention of photoaging has not been investigated in detail. We sought to investigate whether consumption of rice bran supplement (RBS) can elicit preventive effects against UVB-induced photoaging in vivo. Dorsal skin sections of hairless mice were exposed to UVB over 16 weeks. RBS consumption suppressed UVB-induced wrinkle formation and inhibited the loss of water content and epidermal thickening in the mouse skin. Western blot and immunohistochemical analyses revealed that repeated exposure to UVB upregulated matrix metalloproteinase-13 (MMP-13) and cyclooxygenase-2 (COX-2) expression, while consumption of RBS suppressed MMP-13 and COX-2 expression, as well as mitogen-activated protein kinase (MAPK) signaling pathways. These findings suggest that RBS could be a potential bioactive ingredient in nutricosmetics to inhibit wrinkle formation and water content loss via the suppression of COX-2 and MMP-13 expression.

Phlorotannin supplement decreases wake after sleep onset in adults with self-reported sleep disturbance: A randomized, controlled, double-blind clinical and polysomnographic study.

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).

A novel neurological function of rice bran: a standardized rice bran supplement promotes non-rapid eye movement sleep in mice through histamine H1 receptors.

SCOPE: Although rice bran has been shown to be associated with a wide spectrum of health benefits, to date, there are no reports on its effects on sleep. We investigated the effect of rice bran on sleep and the mechanism underlying this effect. METHODS AND RESULTS: Electroencephalography was used to evaluate the effects of standardized rice bran supplement (RBS) and doxepin hydrochloride (DH), a histamine H1 receptor (H1 R) antagonist used as a positive control, on sleep in mice. The mechanism of RBS action was investigated using knockout (KO) mice and ex vivo electrophysiological recordings. Oral administration of RBS and DH significantly decreased sleep latency and increased the amount of non-rapid eye movement sleep (NREMS) in mice. Similar to DH, RBS fully inhibited H1 R agonist-induced increase in action potential frequency in tuberomammillary nucleus neurons. In H1 R KO mice, neither RBS nor DH administration led to the increase in NREMS and decrease in sleep latency observed in WT mice. These results indicate that the sleep-promoting effect of RBS is completely dependent on H1 R antagonism. CONCLUSIONS: RBS decreases sleep latency and promotes NREMS through the inhibition of H1 R, suggesting that it could be a promising therapeutic agent for insomnia.

Sleep-Promoting Effects and Possible Mechanisms of Action Associated with a Standardized Rice Bran Supplement.

Natural sleep aids are becoming more popular due to the widespread occurrence of sleep disorders. The objective of this study was to assess the sleep-promoting effects of rice bran-a product that is considered as a functional ingredient. To evaluate the sleep-promoting effects of a standardized rice bran supplement (RBS), we employed a pentobarbital-induced sleep test and conducted analyses of sleep architecture. In addition, the effect of RBS on a caffeine-induced sleep disturbance was investigated. Oral administration of RBS (500 and 1000 mg/kg) produced a significant decrease in sleep latency and increase in sleep duration in pentobarbital-induced sleep in mice. Moreover, both RBS (1000 mg/kg) and doxepin hydrochloride (histamine H1 receptor antagonist, 30 mg/kg) counteracted a caffeine-induced sleep disturbance in mice. In terms of sleep phases, RBS (500 mg/kg) promoted non-rapid eye movement sleep for the first 3 h following its administration. Lastly, we unveiled a possible mechanism for RBS action as the hypnotic effect of RBS was blocked by a histamine H1 receptor agonist. The present study revealed sleep-promoting effects of RBS using various animal assays. Such effects seem to be mediated through the histaminergic system. Our findings suggest that RBS may be a promising natural aid for relieving sleep problems.

α-Pinene, a Major Constituent of Pine Tree Oils, Enhances Non-Rapid Eye Movement Sleep in Mice through GABAA-benzodiazepine Receptors.

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 GABAA-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 GABAA 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 GABAA-BZD receptors, and fully antagonized by flumazenil, an antagonist for GABAA-BZD receptor. (-)-α-pinene was found to bind to aromatic residues of α1- and -γ2 subunits of GABAA-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 GABAA-BZD receptors and directly binding to the BZD binding site of GABAA receptor.

Agaricus bisporus attenuates dextran sulfate sodium-induced colitis.

Agaricus bisporus (white button mushroom, WBM) is widely consumed in most countries and is reported to have anti-inflammatory and antioxidant activities. However, little is known regarding its effects in dextran sulfate sodium (DSS)-induced colitis, which are related to dysfunction of intestinal immunity. The aim of the present study was to investigate the effects of WBMs in an animal model of DSS-induced colitis. Male, 4-week-old ICR mice (n=10 per group) were fed a normal diet with or without 10% WBM for 4 weeks, and colitis was induced by 3% DSS in drinking water for 7 days. WBMs prevented DSS-induced shortening of colon length (P=.033) and diminished diarrhea (P=.049) and gross bleeding (P=.001), resulting in a decreased disease activity index. Results of histological analysis showed that WBMs suppressed mucosal damage. In addition, WBMs attenuated the DSS-induced increase in myeloperoxidase activity (P=.012) and upregulation of proinflammatory cytokine tumor necrosis factor-α (P=.020) in the colon segment. Taken together, these findings suggest a possible role for the WBM as an immunomodulator that can prevent and/or treat ulcerative colitis.

Ethanolic extract of Taheebo attenuates increase in body weight and fatty liver in mice fed a high-fat diet.

We evaluated whether intake of an ethanolic extract of Taheebo (TBE) from Tabebuia avellanedae protects against body weight increase and fat accumulation in mice with high-fat diet (HFD)-induced obesity. Four-week old male C57BL/6 mice were fed a HFD (25% fat, w/w) for 11 weeks. The diet of control (HFD) mice was supplemented with vehicle (0.5% sodium carboxymethyl cellulose by gavage); the diet of experimental (TBE) mice was supplemented with TBE (150 mg/kg body weight/day by gavage). Mice administered TBE had significantly reduced body weight gain, fat accumulation in the liver, and fat pad weight, compared to HFD mice. Reduced hypertrophy of fat cells was also observed in TBE mice. Mice administered TBE also showed significantly lower serum levels of triglycerides, insulin, and leptin. Lipid profiles and levels of mRNAs and proteins related to lipid metabolism were determined in liver and white adipose tissue of the mice. Expression of mRNA and proteins related to lipogenesis were decreased in TBE-administered mice compared to mice fed HFD alone. These results suggest that TBE inhibits obesity and fat accumulation by regulation of gene expression related to lipid metabolism in HFD-induced obesity in mice.

Curcumin attenuates adhesion molecules and matrix metalloproteinase expression in hypercholesterolemic rabbits.

Curcumin, the yellow substance found in turmeric, possesses antioxidant, anti-inflammation, anticancer, and lipid-lowering properties. Because we hypothesized that curcumin could ameliorate the development of atherosclerosis, the present study focused on the effects and potential mechanisms of curcumin consumption on high-cholesterol diet-induced atherosclerosis in rabbits. During our study, New Zealand white rabbits were fed 1 of 3 experimental diets: a normal diet, a normal diet enriched with 1% cholesterol (HCD), or an HCD supplemented with 0.2% curcumin. At the end of 8 weeks, blood samples were collected to determine the levels of serum lipids, cytokines, and soluble adhesion molecule levels. Gene expression of adhesion molecules and matrix metalloproteinases (MMPs) in aortas were measured by quantitative real-time polymerase chain reaction and Western blot. Compared with the HCD group, rabbits fed an HCD supplemented with 0.2% curcumin had significantly less aortic lesion areas and neointima thickening. Curcumin reduced the levels of total cholesterol, triglyceride, low-density lipoprotein cholesterol, and oxidized low-density lipoprotein cholesterol in serum by 30.7%, 41.3%, 30.4%, and 66.9% (all P < .05), respectively, but did not affect high-density lipoprotein cholesterol levels. In addition, curcumin attenuated HCD-induced CD36 expression, circulating inflammatory cytokines, and soluble adhesive molecule levels. Curcumin reduced the mRNA and protein expression of intracellular adhesion molecule-1, vascular cell adhesion molecule-1, P-selectin, and monocyte chemotactic protein-1, and it inhibited HCD-induced up-regulation of MMP-1, MMP-2, and MMP-9. Our results demonstrate that curcumin exerts an antiatherosclerotic effect, which is mediated by multiple mechanisms that include lowering serum lipids and oxidized low-density lipoprotein, thus modulating the proinflammatory cytokine levels and altering adhesion molecules and MMP gene expression.

Cooked rice inhibits hepatic fat accumulation by regulating lipid metabolism-related gene expression in mice fed a high-fat diet.

Although rice has been shown to have beneficial health effects, little is known about the effect of rice on hepatic lipid accumulation as a carbohydrate source. This study investigated the effects and mechanism of action of cooked rice on high-fat diet (HF)-induced fat accumulation. The C57BL/6 mice were divided into three groups and fed a normal diet (NOR), HF, or HF with cooked rice (HF-CR) for 12 weeks. The HF-CR-fed mice had significantly lower body weight gains and abdominal fat mass compared with the HF-fed mice. Consuming cooked rice resulted in significantly lower serum total cholesterol, low-density lipoprotein cholesterol, hepatic lipid content, and lipid droplet number and size. Cooked rice consumption also suppressed the HF-induced increase in expression of lipogenic genes, such as sterol regulatory element-binding protein 1c (SREBP-1c), fatty acid synthase (FAS), stearoyl CoA desaturase 1 (SCD-1), peroxisome proliferator-activated receptor gamma (PPARγ), and CD36. The expression of cholesterol metabolism-related genes, such as acyl-CoA:cholesterol acyltransferase 1 (ACAT1), were also downregulated in the HF-CR-fed mice. Cooked rice may prevent HF-induced fat accumulation by regulating lipid metabolism-related gene expression, and it may be a useful carbohydrate source for preventing nonalcoholic fatty liver disease.

Anthricin Isolated from Anthriscus sylvestris (L.) Hoffm. Inhibits the Growth of Breast Cancer Cells by Inhibiting Akt/mTOR Signaling, and Its Apoptotic Effects Are Enhanced by Autophagy Inhibition.

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.

Eleutheroside E, An Active Component of Eleutherococcus senticosus, Ameliorates Insulin Resistance in Type 2 Diabetic db/db Mice.

Eleutheroside E (EE), a principal component of Eleutherococcus senticosus (ES), has anti-inflammatory and protective effects in ischemia heart. However, it is unknown whether it ameliorates insulin resistance and reduces hyperglycemia in diabetes. This study investigated the effect of EE-containing ES extracts, as well as EE, on hyperglycemia and insulin resistance in db/db mice. EE increased the insulin-provoked glucose uptake in C2C12 myotubes. Moreover, EE improved TNF- α -induced suppression of glucose uptake in 3T3-L1 adipocytes. Five-week-old db/db mice were fed a diet consisting of ES extract or EE for 5 weeks. Both were effective in improving serum lipid profiles and significantly decreased blood glucose and serum insulin levels. ES and EE supplementation effectively attenuated HOMA-IR. Glucose tolerance and insulin tolerance tests showed that EE increased insulin sensitivity. Immunohistochemical staining indicated that ES and EE protected pancreatic alpha and beta cells from diabetic damage. In addition, ES and EE improved hepatic glucose metabolism by upregulating glycolysis and downregulating gluconeogenesis in obese type 2 diabetic mice. These data suggest that EE mediates the hyperglycemic effects of ES by regulating insulin signaling and glucose utilization. The beneficial effects of EE may provide an effective and powerful strategy to alleviate diabetes.