Phytochemical profiling of Symplocos tanakana Nakai and S. sawafutagi Nagam. leaf and identification of their antioxidant and anti-diabetic potential.

Symplocos sp. contains various phytochemicals and is used as a folk remedy for treatment of diseases such as enteritis, malaria, and leprosy. In this study, we discovered that 70% ethanol extracts of Symplocos sawafutagi Nagam. and S. tanakana Nakai leaves have antioxidant and anti-diabetic effects. The components in the extracts were profiled using high-performance liquid chromatography coupled to electrospray ionization and quadrupole time-of-flight mass spectrometry; quercetin-3-O-(6''-O-galloyl)-ß-d-galactopyranoside (6) and tellimagrandin II (7) were the main phenolic compounds. They acted as strong antioxidants with excellent radical scavenging activity and as inhibitors of non-enzymatic advanced glycation end-products (AGEs) formation. Mass fragmentation analysis demonstrated that compounds 6 and 7 could form mono- or di-methylglyoxal adducts via reaction with methylglyoxal, which is a reactive carbonyl intermediate and an important precursor of AGEs. In addition, compound 7 effectively inhibited the binding between AGE2 and receptor for AGEs as well as the activity of α-glucosidase. Enzyme kinetic study revealed that compound 7 acts as a competitive inhibitor of α-glucosidase, through interaction with the active site of the enzyme. Therefore, compounds 6 and 7, the major constituents of S. sawafutagi and S. tanakana leaves, are promising for developing drugs for preventing or treating diseases caused by aging and excessive sugar consumption.

Phytoestrogen Coumestrol Selectively Inhibits Monoamine Oxidase-A and Amyloid ß Self-Aggregation.

Pueraria lobata leaves contain a variety of phytoestrogens, including flavonoids, isoflavonoids, and coumestan derivatives. In this study, we aimed to identify the active ingredients of P. lobata leaves and to elucidate their function in monoamine oxidase (MAO) activation and Aß self-aggregation using in vitro and in silico approaches. To the best of our knowledge, this is the first study to elucidate coumestrol as a selective and competitive MAO-A inhibitor. We identified that coumestrol, a coumestan-derivative, exhibited a selective inhibitory effect against MAO-A (IC50 = 1.99 ± 0.68 µM), a key target protein for depression. In a kinetics analysis with 0.5 µg MAO-A, 40-160 µM substrate, and 25 °C reaction conditions, coumestrol acts as a competitive MAO-A inhibitor with an inhibition constant of 1.32 µM. During an in silico molecular docking analysis, coumestrol formed hydrogen bonds with FAD and pi-pi bonds with hydrophobic residues at the active site of the enzyme. Moreover, based on thioflavin-T-based fluorometric assays, we elucidated that coumestrol effectively prevented self-aggregation of amyloid beta (Aß), which induces an inflammatory response in the central nervous system (CNS) and is a major cause of Alzheimer's disease (AD). Therefore, coumestrol could be used as a CNS drug to prevent diseases such as depression and AD by the inhibition of MAO-A and Aß self-aggregation.

Genome-enabled discovery of anthraquinone biosynthesis in Senna tora.

Senna tora is a widely used medicinal plant. Its health benefits have been attributed to the large quantity of anthraquinones, but how they are made in plants remains a mystery. To identify the genes responsible for plant anthraquinone biosynthesis, we reveal the genome sequence of S. tora at the chromosome level with 526 Mb (96%) assembled into 13 chromosomes. Comparison among related plant species shows that a chalcone synthase-like (CHS-L) gene family has lineage-specifically and rapidly expanded in S. tora. Combining genomics, transcriptomics, metabolomics, and biochemistry, we identify a CHS-L gene contributing to the biosynthesis of anthraquinones. The S. tora reference genome will accelerate the discovery of biologically active anthraquinone biosynthesis pathways in medicinal plants.

The effects of nattokinase supplementation on collagen-epinephrine closure time, prothrombin time and activated partial thromboplastin time in nondiabetic and hypercholesterolemic subjects.

The aim of this study was to investigate whether supplementation with nattokinase, which is considered one of the most active functional ingredients found in natto, alters hemostatic factors. Subjects presenting with hypercholesterolemia (serum cholesterol: 200-280 mg dL-1) were randomly divided into nattokinase and placebo groups (n = 50, respectively). No significant between-group differences were found at baseline in collagen-epinephrine closure time (C-EPI CT), prothrombin time (PT), or activated partial thromboplastin time (aPTT). After 8 weeks of treatment, the nattokinase group exhibited significant increases in C-EPI CT, PT, and aPTT. The nattokinase group showed significantly greater increases in C-EPI CT (P = 0.001) and aPTT (P = 0.016) than the placebo group. Moreover, at 8 weeks, the nattokinase group showed a significantly higher C-EPI CT than the placebo group (P = 0.001). Additionally, a significant correlation between PT and aPTT was observed (r = 0.491, P < 0.001). In conclusion, nattokinase supplementation was associated with prolonged C-EPI CT and aPTT in nondiabetic and borderline-to-moderate hypercholesterolemic subjects.

Associations of Dietary Riboflavin, Niacin, and Retinol with Age-related Hearing Loss: An Analysis of Korean National Health and Nutrition Examination Survey Data.

Because age-related hearing loss (ARHL) is irreversible, prevention is very important. Thus, investigating modifying factors that help prevent ARHL is critical for the elderly. Nutritional status or nutritional factors for the elderly are known to be associated with many problems related to aging. Emerging studies suggest that there was the interaction between nutrition and ARHL. We aimed to investigate the possible impact of dietary nutrients on ARHL using data from the fifth Korean National Health and Nutrition Examination Survey (KNHANES) which included 4742 subjects aged ≥ 65 years from 2010 to 2012. All participants underwent an otologic examination, audiologic evaluation, and nutritional survey. The associations between ARHL and nutrient intake were analyzed using simple and multiple regression models with complex sampling adjusted for confounding factors, such as BMI, smoking status, alcohol consumption, and history of hypertension and diabetes. Higher intake groups of riboflavin, niacin and retinol was inversely associated with ARHL prevalence (riboflavin aOR, 0.71; 95% CI, 0.54-0.94; p = 0.016, niacin aOR, 0.72; 95% CI, 0.54-0.96; p = 0.025, retinol aOR 0.66; 95% CI, 0.51-0.86; p = 0.002, respectively). Our findings suggest the recommended intake levels of riboflavin, niacin, and retinol may help reduce ARHL in the elderly.

Corrigendum to "A Hop Extract Lifenol® Improves Postmenopausal Overweight, Osteoporosis, and Hot Flash in Ovariectomized Rats".

[This corrects the article DOI: 10.1155/2018/2929107.].

Hydrogen Water Drinking Exerts Antifatigue Effects in Chronic Forced Swimming Mice via Antioxidative and Anti-Inflammatory Activities.

PURPOSE: This study was performed to evaluate antifatigue effect of hydrogen water (HW) drinking in chronic forced exercise mice model. MATERIALS AND METHODS: Twelve-week-old C57BL6 female mice were divided into nonstressed normal control (NC) group and stressed group: (purified water/PW-treated group and HW-treated group). Stressed groups were supplied with PW and HW, respectively, ad libitum and forced to swim for the stress induction every day for 4 consecutive weeks. Gross antifatigue effects of HW were assessed by swimming endurance capacity (once weekly for 4 wk), metabolic activities, and immune-redox activities. Metabolic activities such as blood glucose, lactate, glycogen, blood urea nitrogen (BUN), and lactate dehydrogenase (LDH) as well as immune-redox activities such as reactive oxygen species (ROS), nitric oxide (NO), glutathione peroxidase (GPx), catalase, and the related cytokines were evaluated to elucidate underlying mechanism. Blood glucose and lactate were measured at 0 wk (before swimming) and 4 wk (after swimming). RESULTS: HW group showed a higher swimming endurance capacity (p < 0.001) than NC and PW groups. Positive metabolic effects in HW group were revealed by the significant reduction of blood glucose, lactate, and BUN in serum after 4 wk (p < 0.01, resp.), as well as the significant increase of liver glycogen (p < 0.001) and serum LDH (p < 0.05) than PW group. In parallel, redox balance was represented by lower NO in serum (p < 0.01) and increased level of GPx in both serum and liver (p < 0.05) than PW group. In line, the decreased levels of serum TNF-α (p < 0.01), IL-6, IL-17, and liver IL-1ß (p < 0.05) in HW group revealed positive cytokine profile compared to PW and NC group. CONCLUSION: This study shows antifatigue effects of HW drinking in chronic forced swimming mice via metabolic coordination and immune-redox balance. In that context, drinking HW could be applied to the alternative and safety fluid remedy for chronic fatigue control.

A Hop Extract Lifenol® Improves Postmenopausal Overweight, Osteoporosis, and Hot Flash in Ovariectomized Rats.

Objective: In order to assess the effectiveness of a hop extract (HE) for postmenopausal symptoms, the effects of Lifenol on ovariectomy-induced osteoporosis, hyperlipidemia, body weight increase, and hot flash were investigated in rats. Methods: Female Sprague-Dawley rats were ovariectomized and subjected to a daily scheduled exercise training (15 min at 15 m/min) or treated with HE (30 or 100 mg/kg, oral) or 17ß-estradiol (100 µg/kg, intraperitoneal) for 12 weeks. Body and visceral fat weights, serum lipid profiles, osteoporotic parameters in serum, and femoral bones were analyzed. Separately, forced running-induced dermal and rectal temperatures and blood flow velocity were measured in ovariectomized rats. Results: Ovariectomy increased blood lipids including triglycerides, total cholesterol, and low-density lipoproteins, leading to visceral fat accumulation and overweight. Estrogen depletion caused osteoporosis, displaying decreased femoral bone weight, bone mineral density and content, and blood phosphorus level. The disturbances in lipid metabolism and bone resorption were recovered by treatment with HE in a dose-dependent manner. In addition, HE treatment shortened the duration of forced running-induced alterations in skin and rectal temperatures by reducing blood flow velocity. Conclusion: The results indicate that HE attenuated overweight, osteoporosis, and hot flash in estrogen-deficient animals by regulating blood lipid profile and fat accumulation, blood estrogen and bone resorption factors, and dermal blood flow.

Comparative effects of plant oils and trans-fat on blood lipid profiles and ischemic stroke in rats.

Since plant oils are believed to be better than animal fats for cerebrovascular and cardiovascular diseases, the effects of various plant oils and trans-fat on blood lipid profiles and ischemic stroke were investigated. Sprague-Dawley rats were fed a diet containing the oils or trans-fat, and then body weights, blood lipids, and effects on brain infarction and physical dysfunction induced by middle cerebral artery occlusion (MCAO) were analyzed. All the oils and trans-fat, except perilla oil, significantly increased body fats and body weight gain. Sesame oil and trans-fat specifically increased blood cholesterols and triglycerides, respectively, while perilla oil decreased both cholesterols and triglycerides. Perilla oil not only attenuated cerebral infarction, but also restored locomotor activity and rota-rod performances of MCAO rats. It is suggested that perilla oil among oils and fats could be the first choice to reduce the risk of metabolic syndrome and ischemic stroke.

Cereboost™, an American ginseng extract, improves cognitive function via up-regulation of choline acetyltransferase expression and neuroprotection.

In Alzheimer disease (AD), amyloid-beta (Aß) peptides induce the degeneration of presynaptic cholinergic system, in which decreased activity of enzyme choline acetyltransferase (ChAT) responsible for acetylcholine synthesis is observed. Cereboost™, an extract of American ginseng extract, contains a high concentration of Rb1 ginsenoside which is a well-known ingredient improving human cognitive function. We investigated the effects of Cereboost™ on learning and memory function of mice challenged with an Aß1-42 peptide and the underlying mechanisms in vitro. Cereboost™ protected against Aß1-42-induced cytotoxicity in F3.ChAT stem cells, and enhanced the ChAT gene expression. Aß1-42 injection into the mouse brain impaired the cognitive function, which was recovered by oral administration of Cereboost™. In addition, Cereboost™ restored brain microtubule-associated protein 2 and synaptophysin as well as acetylcholine concentration. The results demonstrate that Cereboost™ administration recovered the cognitive function of AD model animals by enhancing acetylcholine level via ChAT gene expression and neuroprotection.

Allohumibacter endophyticus gen. nov., sp. nov., isolated from the root of wild Artemisia princeps (mugwort).

A novel actinobacterium designated strain MWE-A11T was isolated from the root of wild Artemisia princeps (mugwort). The isolate was aerobic, Gram-stain-positive and short rod-shaped, and the colonies were yellow and circular with entire margin. Strain MWE-A11T grew at 15-37 °C and pH 6.0-8.0. The predominant isoprenoid quinones were MK-11 and MK-10. The predominant fatty acids were anteiso-C15:0 and iso-C16:0, and the DNA G+C content was 68.8 mol%. The main polar lipids were diphosphatidylglycerol, phosphatidylglycerol and an unidentified glycolipid. The peptidoglycan contained 2,4-diaminobutyric acid as the diagnostic diamino acid, and the acyl type was glycolyl. Phylogenetic analyses based on 16S rRNA gene sequence comparisons indicated that strain MWE-A11T was affiliated with the family Microbacteriaceae, and was most closely related to the type strains of Humibacter antri (96.4% 16S rRNA gene sequence similarity), Herbiconiux moechotypicola (96.3%), Leifsonia soli (96.3%), Leifsonia lichenia (96.2%), Leifsonia xyli subsp. cynodontis (96.1%), Microbacterium testaceum (96.0%) and Humibacter albus (96.0%). However, the combination of chemotaxonomic properties clearly distinguished strain MWE-A11T from the related taxa at genus level. Accordingly, Allohumibacter endophyticus gen. nov., sp. nov. is proposed to accommodate a new member of the family Microbacteriaceae. The type strain of the type species is MWE-A11T (=JCM 19371T=KCTC 29232T).

Comparative effects of plant oils on the cerebral hemorrhage in stroke-prone spontaneously hypertensive rats.

OBJECTIVES: Since oils and fats can induce metabolic syndrome, leading to cardiovascular and cerebrovascular diseases, the present study was performed to find out whether the plant oils affect the cerebral hemorrhage in stroke-prone spontaneously hypertensive (SHR-SP) rats. METHODS: From 47 days of age, male SHR-SP rats were given drinking water containing 1% NaCl to induce hypertension, and simultaneously fed semi-purified diets containing 10% perilla oil, canola oil, or shortening. The onset time of convulsion following cerebral hemorrhage was recorded, and the areas of hemorrhage and infarction were analyzed in the stroke brains. RESULTS: In comparison with 58-day survival of SHR-SP rats during feeding NaCl alone, perilla oil extended the survival time to 68.5 days, whereas canola oil shortened it to 45.7 days. Feeding perilla oil greatly reduced the total volume of cerebral hemorrhage from 17.27% in the control group to 4.53%, while shortening increased the lesions to 21.23%. In a microscopic analysis, perilla oil also markedly decreased the hemorrhagic and infarction lesions to 1/10 of those in control rats, in contrast to an exacerbating effect of shortening. In blood analyses, perilla oil reduced blood total cholesterol and low-density lipoproteins which were increased in SHR-SP, but canola oil further increased them and markedly lowered platelet counts. DISCUSSION: Perilla oil delayed and attenuated cerebral hemorrhage by improving hyperlipidemia in hypertensive stroke animals, in contrast to the aggravating potential of canola oil and shortening. It is suggested that perilla oil should be the first choice oil for improving metabolic syndrome in hypertensive persons at risk of hemorrhagic stroke.

The efficacy and safety of systemic injection of Ginkgo biloba extract, EGb761, in idiopathic sudden sensorineural hearing loss: a randomized placebo-controlled clinical trial.

Steroids are currently the most frequently accepted agents for idiopathic sudden sensorineural hearing loss (ISSNHL). However, the therapeutic effect of steroids is not always satisfactory. In this pilot study, we evaluated whether systemic treatment with Ginkgo biloba extract (EGb761) has an additive therapeutic effect in patients receiving a systemic steroid due to ISSNHL. A multicenter, randomized, double-blind clinical trial was performed. Fifty-six patients with ISSNHL were allocated to either EGb761 or placebo. In both groups, methylprednisolone was administered for 14 days. EGb761 was infused intravenously for 5 days in the EGb761 group, while the same amount of normal saline was infused in the placebo group. For the efficacy evaluation, pure-tone audiometry, speech audiometry, tinnitus handicap inventory (THI) and short form-36 health (SF-36) survey outcomes were obtained before administration and on days 3, 5, 14 and 28 of administration. Twenty-four patients in each group completed the study protocol. There was no difference in hearing loss between the two groups before treatment. At day 28, air conduction threshold values in the placebo and EGb761 groups were 34.63 ± 28.90 and 23.84 ± 25.42 dB, respectively (p = 0.082). Speech discrimination scores in the placebo and EGb761 groups were 69.17 ± 40.89 and 87.48 ± 28.65 %, respectively (p = 0.050). THI and SF-36 scores in the placebo and EGb761 groups were similar. Although a combination of steroid and EGb761 for initial treatment did not show better pure tone threshold, compared with steroid alone, speech discrimination was significantly improved in combination therapy. Further studies will be needed to know if addition of EGb761 actually improves the outcome of ISSNHL treatment.

Effects of scanner acoustic noise on intrinsic brain activity during auditory stimulation.

INTRODUCTION: Although the effects of scanner background noise (SBN) during functional magnetic resonance imaging (fMRI) have been extensively investigated for the brain regions involved in auditory processing, its impact on other types of intrinsic brain activity has largely been neglected. The present study evaluated the influence of SBN on a number of intrinsic connectivity networks (ICNs) during auditory stimulation by comparing the results obtained using sparse temporal acquisition (STA) with those using continuous acquisition (CA). METHODS: Fourteen healthy subjects were presented with classical music pieces in a block paradigm during two sessions of STA and CA. A volume-matched CA dataset (CAm) was generated by subsampling the CA dataset to temporally match it with the STA data. Independent component analysis was performed on the concatenated STA-CAm datasets, and voxel data, time courses, power spectra, and functional connectivity were compared. RESULTS: The ICA revealed 19 ICNs; the auditory, default mode, salience, and frontoparietal networks showed greater activity in the STA. The spectral peaks in 17 networks corresponded to the stimulation cycles in the STA, while only five networks displayed this correspondence in the CA. The dorsal default mode and salience networks exhibited stronger correlations with the stimulus waveform in the STA. CONCLUSIONS: SBN appeared to influence not only the areas of auditory response but also the majority of other ICNs, including attention and sensory networks. Therefore, SBN should be regarded as a serious nuisance factor during fMRI studies investigating intrinsic brain activity under external stimulation or task loads.

Nocardioides endophyticus sp. nov. and Nocardioides conyzicola sp. nov., isolated from herbaceous plant roots.

Two Gram-stain-positive, non-motile, non-spore-forming, rod-shaped actinobacterial strains were isolated from the surface-sterilized roots of mugwort (Artemisia princeps) and horse-weed (Conyza canadensis), and subjected to taxonomic characterization. 16S rRNA gene sequence analysis indicated that the isolates, designated MWE 3-5(T) and HWE 2-02(T), should be placed in the genus Nocardioides of the family Nocardioidaceae. The strains were closely related to Nocardioides hankookensis DS-30(T), which exhibited 16S rRNA gene sequence similarity values of 97.99 and 99.09 % with strains MWE 3-5(T) and HWE 2-02(T), respectively. The genome relatedness of N. hankookensis DS-30(T) with strain MWE 3-5(T) was 35.8 %, and that with strain HWE 2-02(T) was 36.4 %, whereas that between the two isolates was 43.2 %. Strains MWE 3-5(T) and HWE 2-02(T) possessed MK-8(H4) as the major isoprenoid quinone, and ll-diaminopimelic acid in the cell-wall peptidoglycan. The main fatty acids were iso-C16 : 0, iso-C17 : 0 and C18 : 1ω9c for strain MWE 3-5(T) and iso-C16 : 0, 10-methyl C18 : 0 and C18 : 1ω9c for strain HWE 2-02(T). Based on phenotypic, genotypic and phylogenetic studies, the following two novel species are proposed: Nocardioides endophyticus sp. nov. (type strain, MWE 3-5(T) = KCTC 29122(T) = JCM 18532(T)) and Nocardioides conyzicola sp. nov. (type strain, HWE 2-02(T) = KCTC 29121(T) = JCM 18531(T)).

Endothelium-dependent vasodilatory and hypotensive effects of Crotalaria sessiliflora L. in rats.

The aim of the present study was to investigate the vasoactive effect of Crotalaria sessiliflora L. extract (CSE) on rats and its mechanism when combining in vivo and in vitro approaches. CSE (0.5-5 mg/ml) induced concentration-dependent relaxation on endothelium-intact thoracic aortic rings precontracted with phenylephrine (PE, 10(-5) M). This effect disappeared with the removal of functional endothelium. Pretreatment of the aortic strips with either N(G)-nitro-L-arginine (L-NNA, 10(-5) M) or methylene blue (10(-5) M) significantly reduced the relaxation induced by CSE. The endothelium-dependent relaxation caused by CSE was associated with production of cGMP. CSE (5 mg/ml) increased the production of cGMP in endothelium-intact aortic rings and this effect was significantly attenuated by L-NNA (10(-5) M) and methylene blue (10(-5) M). Relaxation in response to CSE in strips precontracted with PGF2alpha (3x10(-5) M) was eliminated by removing extracellular Ca2+ and significantly reduced by pretreatment with ruthenium red (10(-5) M). In in vivo tests, injection of 40 mg/kg of CSE induced an increase in plasma NO production, and this effect was blocked by L-NNA. Furthermore, CSE produced dose-dependent and transient decrease in blood pressure in normotensive rats and this effect was blocked by atropine as well as L-NNA. These findings suggest that CSE induces endothelium-dependent relaxation via NO/cGMP signaling by promoting extracellular Ca2+ influx and the release of Ca2+ from intracellular stores of endothelium, probably due to endothelial muscarinic receptor activation.