and its ingredient biopterin glucoside improved insulin sensitivity in non-alcoholic steatohepatitis model.

Non-alcoholic steatohepatitis is the chronic liver disease leading to cirrhosis and cancer and its prevalence is increasing. Some agents are under clinical trials for non-alcoholic steatohepatitis treatment. We previously reported effectively prevented non-alcoholic steatohepatitis progression in our model rats.

[Antinociceptive effect of docosahexaenoic acid (DHA) through long fatty acid receptor G protein-coupled receptor 40 (GPR40)].

Fatty acids, one class of essential nutrients for humans, are an important source of energy and an essential component of cell membranes. They also function as signal transduction molecules in a variety of biological phenomena. The important functional role of fatty acids in both onset and suppression of pain has become increasingly apparent in recent years.

Oral administration of eicosapentaenoic acid or docosahexaenoic acid modifies cardiac function and ameliorates congestive heart failure in male rats.

This study assessed the effects of eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) on normal cardiac function (part 1) and congestive heart failure (CHF) (part 2) through electrocardiogram analysis and determination of EPA, DHA, and arachidonic acid (AA) concentrations in rat hearts. In part 2, pathologic assessments were also performed. For part 1 of this study, 4-wk-old male rats were divided into a control group and 2 experimental groups.

Hypothalamic GPR40 signaling activated by free long chain fatty acids suppresses CFA-induced inflammatory chronic pain.

GPR40 has been reported to be activated by long-chain fatty acids, such as docosahexaenoic acid (DHA). However, reports studying functional role of GPR40 in the brain are lacking. The present study focused on the relationship between pain regulation and GPR40, investigating the functional roles of hypothalamic GPR40 during chronic pain caused using a complete Freund's adjuvant (CFA)-induced inflammatory chronic pain mouse model.

[Elucidation of mechanisms underlying docosahexaenoic acid-induced antinociception].

Docosahexaenoic acid (DHA), a predominant of n-3 polyunsaturated fatty acids (n-3 PUFA), has numerous beneficial physiological effects, including neuroprotection and cardiovascular protection. Recently, a possible involvement of n-3 PUFA in pain control has gathered considerable attention because numerous studies have reported a regulatory role of n-3 PUFAs. However, the mechanisms underlying how DHA exerts antinociceptive effect remain unknown.

Effects of squalene/squalane on dopamine levels, antioxidant enzyme activity, and fatty acid composition in the striatum of Parkinson's disease mouse model.

Active oxygen has been implicated in the pathogenesis of Parkinson's disease (PD); therefore, antioxidants have attracted attention as a potential way to prevent this disease. Squalene, a natural triterpene and an intermediate in the biosynthesis of cholesterol, is known to have active oxygen scavenging activities. Squalane, synthesized by complete hydrogenation of squalene, does not have active oxygen scavenging activities.

Anti-oxidative and anti-inflammatory effects of spirulina on rat model of non-alcoholic steatohepatitis.

The pathogenesis of nonalcoholic steatohepatitis (NASH) remains unclear, but accumulating data suggest oxidative stress and the relationship between inflammation and immunity plays a crucial role. The aim of this study is to investigate the spirulina, which is a blue-green algae rich in proteins and other nutritional elements, and its component-phycocyanin effect on a rat model of NASH. NASH model rats were established by feeding male Wistar rats with choline-deficient high-fat diet (CDHF) and intermittent hypoxemia by sodium nitrite challenge after 5 weeks of CDHF.

Water extract of Vitis coignetiae Pulliat leaves attenuates oxidative stress and inflammation in progressive NASH rats.

This study aimed to investigate the therapeutic effects of the water extract of leaves of Vitis coignetiae Pulliat (VCPL) on nonalcoholic steatohepatitis (NASH) with advanced fibrosis, as our previous study exhibited its preventive effect on NASH. The NASH animal model [PCT/JP2007/52477] was prepared by loading recurrent and intermittent hypoxemia stress to a rat with fatty liver, which resembled the condition occurring in patients with obstructive sleep apnea (OSA) and fatty liver, who have a high incidence of NASH. Intermittent hypoxemia stress is regarded as a condition similar to warm ischemia followed by re-oxygenation, which induces oxidative stress (OS).

Involvement of the long-chain fatty acid receptor GPR40 as a novel pain regulatory system.

G-protein receptor (GPR) 40 is known to be activated by docosahexaenoic acid (DHA). However, reports studying the role and functions (including pain regulation) of GPR40 in the brain are lacking. We investigated the involvement of GPR40 in the brain on DHA-induced antinociceptive effects.

Possible involvement of β-endorphin in docosahexaenoic acid-induced antinociception.

We have previously demonstrated that the n-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) has an antinociceptive effect on various pain stimuli in a naloxone-reversible manner. In the present study, the role of the endogenous opioid peptide β-endorphin in DHA-induced antinociception was examined. DHA-induced antinociception was abolished when mice were pretreated with the μ-opioid receptor antagonist β-funaltrexamine (β-FNA) and the δ-opioid receptor antagonist naltrindole, but not by the κ-opioid receptor antagonist nor-binaltorphimine (nor-BNI) in the acetic acid-induced writhing test.

Effects of docosahexaenoic acid in an experimental rat model of nonalcoholic steatohepatitis.

Docosahexaenoic acid (DHA) regulates the lipid metabolism and inflammation that is closely associated with oxidative stress. The present study investigated the effects of DHA on the development of nonalcoholic steatohepatitis (NASH). To induce fatty liver, rats were fed choline-deficient high-fat diets (CDHF).

Antinociceptive effects of docosahexaenoic acid against various pain stimuli in mice.

Docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid (n-3 PUFAs), is an essential polyunsaturated fatty acid in the central nervous system, and possesses many physiological functions in neurodegenerative diseases. Previously, there are some reports that n-3 PUFAs contribute to pain relief. As the antinociceptive effect of DHA alone has not been reported, this study examined the antinociceptive effect of DHA on various pain stimuli.

A Novel Animal Model of Nonalcoholic Steatohepatitis (NASH): Hypoxemia Enhances the Development of NASH.

Recent reports described a high incidence of nonalcoholic steatohepatitis (NASH) in patients with obstructive sleep apnea. Accordingly, we hypothesized that recurrent and intermittent hypoxemia plays an important role in the pathogenesis of NASH. Our objective was construction of a practical and accurate experimental model to reproduce the key features of NASH in humans.

Beneficial Effects of Fermented Green Tea Extract in a Rat Model of Non-alcoholic Steatohepatitis.

Oxidative stress is frequently considered as a central mechanism of hepatocellular injury in non-alcoholic steatohepatitis (NASH). The aim of this study was to investigate the effects of fermented green tea extracts (FGTE) on NASH. Rats were fed a choline-deficient high-fat diet for 4 weeks to nutritionally generate fatty livers.

Beneficial effects of Vitis coignetiae Pulliat leaves on nonalcoholic steatohepatitis in a rat model.

Vitis coignetiae Pulliat (Yamabudo) is used as a health juice and wine based on the abundant polyphenols and anthocyanins in its fruit. However, it is not known whether the leaves of this plant confer similar benefits. This study investigated the hepatoprotective effects of aqueous extracts from Vitis coignetiae Pulliat leaves (VCPL) in an animal model of nonalcoholic steatohepatitis (NASH).

Docosahexaenoic acid ethyl ester enhances 6-hydroxydopamine-induced neuronal damage by induction of lipid peroxidation in mouse striatum.

Superoxide and hydroxyl radicals are implicated in the pathogenesis of Parkinson disease, and induction of lipid peroxidation is an important factor in progression of this disease. Docosahexaenoic acid (DHA) is a key component of the cell membrane, and its peroxidation is inducible due to the double-bond chemical structure. However, DHA has neuroprotective effects.

Inhibitory effect of fermented papaya preparation on hydroxyl radical generation from methylguanidine.

We have previously shown that extremely high level of guanidino compounds such as methylguanidine (MG), known as a neurotoxin and also a nephrotoxin, generate reactive oxygen species (ROS) using an electron spin resonance (ESR) technique with spin trap 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). In this in vitro study, the inhibitory effect of fermented papaya preparation (SAIDO-PS501:PS-501) on hydroxyl radical (.OH) generation from MG was examined using an ESR spectrometry, and it was found that PS-501 suppressed .

Inhibitory effect of antioxidants on hydroxyl radical generation from methylguanidine: an ESR study.

Methylguanidine (MG) is known as not only a nephrotoxin but also as a neurotoxine. We have previously showed that MG itself generates hydroxyl radicals (*OH) in an in vitro study. In this study, we examined the inhibitory effects of ascorbate, EPC-K(1) (alpha-tocopheryl-L-ascorbate-2-O-phosphate diester), Trolox (water-soluble vitamin E analogue), and glutathione (GSH) on *OH generation from MG using an electron spin resonance (ESR) spectrometry with spin trap 5,5-dimethyl-1-pyrroline-N-oxide (DMPO).

Incorporation and accumulation of docosahexaenoic acid from the medium by Pichia methanolica HA-32.

Yeast species were screened for the incorporation and accumulation of docosahexaenoic acid (DHA) with a yeast-malt medium containing 0.5% free fatty acid prepared from fish oil (DHA, 28% of total fatty acids in fish oil). The most suitable strain was Pichia methanolica HA-32.