Soymilk yogurt fermented using Pediococcus pentosaceus TOKAI 759 m improves mice gut microbiota and reduces pro-inflammatory cytokine production.

This study aimed to determine the anti-inflammatory activities and bioactive compounds of soymilk yogurt prepared using Lactiplantibacillus plantarum TOKAI 17 or Pediococcus pentosaceus TOKAI 759 m. Mice were divided into five groups: normal diet (ND), soymilk (SM), soymilk yogurt using L. plantarum TOKAI 17 (SY 17) or P. pentosaceus TOKAI 759 m (SY 759 m), and 0.5 × 109 cells of each starter strain (BC 17 or BC759m). In the SY 759 m group, the serum pro-inflammatory cytokine levels and the cytotoxicity of natural killer cells were attenuated compared to the ND group. In the cecum microbiota, the abundances of butyrate-producing bacteria increased in the SY 759 m and BC 17 groups. Furthermore, SY 759 m metabolites contained high levels of aglycone isoflavone, adenine and showed a significant decrease in CCL-2 and IL-6 production in LPS-induced macrophage. In conclusion, soymilk yogurt produced using P. pentosaceus TOKAI 759 m modulates the gut microbiota and can potentially prevent pro-inflammatory cytokine production.

Regulatory effects of antioxidants on indoxyl sulfate-enhanced intracellular oxidation and impaired phagocytic activity in differentiated U937 human macrophage cells.

Indoxyl sulfate (IS), a uremic toxin, is a physiologically active sulfated metabolite, specifically in kidney failure patients. Our previous studies have shown that IS downregulates phagocytic immune function in a differentiated HL-60 human macrophage cell model. However, it remains unclear whether IS exerts similar effects on macrophage function in other cell types or in lipopolysaccharide (LPS)-sensitive immune cell models. Therefore, this study aimed to investigate the effects of IS on intracellular oxidation levels and phagocytic activity in a differentiated U937 human macrophage cell model, both in the absence and presence of LPS. Our results demonstrated that IS significantly increases intracellular oxidation levels and decreases phagocytic activity, particularly in cells activated by LPS. Furthermore, we found that 2-acetylphenothiazine, an NADH oxidase inhibitor, attenuates the effects of IS in LPS-activated macrophage cells. Representative antioxidants, trolox, α-tocopherol, and ascorbic acid, significantly mitigated the effects of IS on the macrophages responding to LPS.

Lactic acid bacterial exopolysaccharides strongly bind histamine and can potentially be used to remove histamine contamination in food.

The symptoms of foodborne histamine poisoning are similar to those of IgE-mediated food allergies. In this study, we investigated the histamine-binding capacity of lactic acid bacteria (LAB) strains as potential preventive agents against histamine poisoning. Histamine biosorption capacity was determined for 16 LAB strains. Leuconostoc mesenteroides TOKAI 51 m, Lactobacillus paracasei TOKAI 65 m, Lactobacillus plantarum TOKAI 111 m and Pediococcus pentosaceus TOKAI 759 m showed especially high biosorption rates and reached saturation within 30 min. Adsorption isotherms showed better conformance to the Freundlich model than to the Langmuir model. Analyses after heat, periodic acid and guanidine hydrochloride treatments suggested that histamine was bound to the bacterial cell surface. HPLC analysis revealed that exopolysaccharides produced by Lact. paracasei TOKAI 65 m strongly bound to histamine. In the detachment test with 1 mol l-1 HCl solution, the dissociation rate of histamine for Lact. paracasei TOKAI 65 m was <10 %. This strain is presumably a suitable candidate for use against histamine poisoning.

A New Glycosidic Acid, Muricatic Acid D, and Resin Glycosides, Muricatins X and XI, from the Crude Resin Glycoside Fraction of the Seeds of Ipomoea muricata.

Alkaline hydrolysis of crude resin glycoside fraction of the seeds of Ipomoea muricata (L.) Jacq. (Convolvulaceae) yielded a new glycosidic acid, muricatic acid D; three known glycosidic acids, namely, muricatic acids A, B, and C; and three known organic acids, namely, isobutyric, 2S-methylbutyric, and 2S-methyl-3S-hydroxybutyric acid. Two new genuine resin glycosides with macrolactone structures (jalapins), muricatins X and XI, were also isolated from the fraction. Their structures were determined using spectroscopic data and chemical evidence.

Investigation of the effects of indoxyl sulfate, a uremic toxin, on the intracellular oxidation level and phagocytic activity using an HL-60-differentiated human macrophage cell model.

Indoxyl sulfate (IS), a uremic toxin, is a sulfate-conjugated metabolite originated from tryptophan. Accumulating uremic toxins may worsen renal diseases and further complicate related disorders including impaired immune functions under oxidative stress conditions. However, it has remained unclear whether or not IS can directly cause the cellular immune dysfunction. We investigated the effects of IS on the intracellular oxidation level and phagocytic activity in a HL-60-differantiated human macrophage cell model. Incubation of the cells in the presence of IS resulted in increasing intracellular oxidation level and decreasing phagocytic activity. In addition to inhibitors for NADH oxidase (NOX), organic anion transporting polypeptide2B1 (OATP2B1), protein kinase C (PKC), and phosphoinositide 3-kinase (PI3K), a representative antioxidant Trolox, was also shown to significantly relieve the IS-induced oxidation and restore weakened phagocytosis. Collectively, IS may directly down-regulate the phagocytic immune function of macrophages through the oxidation mechanisms including OATP2B1, PKC, PI3K, and NOX pathways. Abbreviations: CKD: Chronic kidney disease; IS: Indoxyl sulfate; ROS: Reactive oxygen species; NOX: NADH oxidase; OATP2B1: Organic anion transporting polypeptide2B1; PKC: Protein kinase C; PI3K: Phosphoinositide 3-kinase; 2-APT: 2-acetylphenothiazine.

Increased phenolic content and antioxidant capacity of the heated leaves of yacon (Smallanthus sonchifolius).

We investigated the content of phenolic compounds and antioxidant capacity of two batches of non-heated and heated leaves of the yacon cultivar "Andes no yuki", grown in Japan. Lyophilized yacon leaves heated at 160°C for 20 min and 100°C for 60 min had a 1.96 to 9.69-times higher total phenolic content than that of the non-heated leaves. Heated leaves exhibited a 1.98 to 4.07-times higher antioxidant capacity than that of the non-heated leaves in three different free radical scavenging assays. Heated leaves were more efficient at attenuating the superoxide anion radical production in human granulocytic cells than the non-heated leaves. High-performance liquid chromatography analysis revealed that, in the heated leaves, the caffeic acid content was 2.13 to 3.64-times higher and the chlorogenic acid content was slightly lower than those in the non-heated leaves. Hence, heat processing may affect the active constituent contents in yacon leaves, potentiating its antioxidant capacity.Abbreviations: ABTS+: 2,2'-azinobis(2-ethylbenzothiazoline-6-sulfonic acid) cation; DPPH: 1,1-diphenyl-2-picrylhydrazyl, HPLC: high-performance liquid chromatography; NBT: nitroblue tetrazolium; O2-: superoxide anion; PMA: phorbol 12-myristate 13-acetate; PMS: phenazine methosulfate; TEAC: Trolox equivalent antioxidant capacity.

Syntenin: PDZ Protein Regulating Signaling Pathways and Cellular Functions.

Syntenin is an adaptor-like molecule that has two adjacent tandem postsynaptic density protein 95/Discs large protein/Zonula occludens 1 (PDZ) domains. The PDZ domains of syntenin recognize multiple peptide motifs with low to moderate affinity. Many reports have indicated interactions between syntenin and a plethora of proteins. Through interactions with various proteins, syntenin regulates the architecture of the cell membrane. As a result, increases in syntenin levels induce the metastasis of tumor cells, protrusion along the neurite in neuronal cells, and exosome biogenesis in various cell types. Here, we review the updated data that support various roles for syntenin in the regulation of neuronal synapses, tumor cell invasion, and exosome control.

Unique antioxidant effects of herbal leaf tea and stem tea from Moringa oleifera L. especially on superoxide anion radical generation systems.

This study aimed to investigate the unique antioxidative effects of Japanese moringa products, herbal leaf tea and stem tea, using established free radical assays, focusing on superoxide anion (O2-) radical generation systems. Hot-water extracts from moringa teas resulted in different but lower scavenging activities than Trolox in four synthetic free radical models. Interestingly, these extracts further showed higher O2- radical scavenging effects than Trolox in the phenazine methosulfate-NADH-nitroblue tetrazolium and xanthine oxidase assay systems. Incubating human neutrophils in the presence of these tea extracts rather than Trolox effectively suppressed cellular O2- radical generation. Among the eight known phenolic constituents of moringa leaves, caffeic acid and chlorogenic acid may be responsible for the O2-specific radical scavenging capacity stronger than that of Trolox. These results suggest that moringa herbal teas are a good source of natural antioxidants for preventing O2- radical-mediated disorders. Abbreviations: O2-: superoxide anion; ROS: reactive oxygen species; H2O2: hydrogen peroxide; XOD: xanthine oxidase; DPPH: 1,1-diphenyl-2-picrylhydrazyl; ABTS+: 2,2'-azinobis(2-ethylbenzothiazoline-6-sulfonic acid) cation; CPZ+: chlorpromazine cation; PMS: phenazine methosulfate; NBT: nitroblue tetrazolium; PMA: phorbol 12-myristate 13-acetate.

Acylated Glycosidic Acid Methyl Esters Generated from the Convolvulin Fraction of Rhizoma Jalapae Braziliensis by Treatment with Indium(III) Chloride in Methanol.

Four hexaglycosides of methyl 3S,12S-dihydroxyhexadecanoate (1-4) were provided after treatment of the crude convolvulin fraction from Rhizoma Jalapae Braziliensis (the root of Ipomoea operculata (GOMES) MART., Convolvulaceae) with indium(III) chloride in methanol. The structures of 1-4 were elucidated on the basis of spectroscopic and chemical methods. Their sugar moieties were partially acylated with organic acids including (3S,9R)-3,6:6,9-diepoxydecanoic (exogonic) acid, (E)-2-methylbut-2-enoic (tiglic) acid, and isovaleric acid.

A New Resin Glycoside, Muricatin IX, from the Seeds of Ipomoea muricata.

A new resin glycoside, named muricatin IX (1), was isolated from the seeds of Ipomoea muricata (L.) JACQ. (Convolvulaceae). The structure of 1 was determined on the basis of spectroscopic data as well as chemical evidence. Compound 1 is the first representative of resin glycosides in which an organic acid connects the sugar moiety and the aglycone moiety to form macrocyclic ester ring.

GPR39-1b, the 5-transmembrane isoform of GPR39 interacts with neurotensin receptor NTSR1 and modifies its function.

G-protein-coupled receptor 39 (GPR39), a member of the ghrelin receptor family, has a full-length isoform GPR39-1a and a truncated isoform GPR39-1b. While GPR39-1a was clarified as a receptor of Zn(2+), the characteristic property of GPR39-1b remains unknown. Therefore, in this study, the molecular functions of GPR39-1b were explored in cell culture. In contrast to GPR39-1a, GPR39-1b showed no response to Zn(2+) stimulation in calcium mobilization assays, suggesting that GPR39-1b is not a functional receptor of Zn(2+). To understand the signaling interaction of GPR39-1b, we investigated the dimerization between the isoforms, and conducted bioluminescence resonance energy transfer (BRET(2)) assays. The results indicated that GPR39-1b homodimerized, but did not heterodimerize with GPR39-1a. We subsequently attempted to search the heterodimeric counterparts of GPR39-1b. Neurotensin receptor 1 (NTSR1) was also targeted as a GPR39-1b interacting partner because of its highly conserved amino acid sequence and mRNA localization, which was similar to GPR39-1b. BRET(2) assays demonstrated that GPR39-1b heterodimerized with NTSR1. To examine the effect of GPR39-1b on NTRS1-mediated cAMP/PKA signaling, we used the cAMP responsive element-luciferase assays and observed that GPR39-1b attenuated neurotensin-induced NTSR1 signaling. Taken together, our results provided a novel regulatory mechanism for GPR39-1b in NTRS1 signaling.

Inhibitory effects of the ethyl acetate extract from bulbs of Scilla scilloides on lipoxygenase and hyaluronidase activities.

CONTEXT: Scilla scilloides Druce (Liliaceae) is a folk medicine to treat dermal inflammation; however, the medicinal properties of this plant have not been completely established. OBJECTIVE: The current study investigates the potent anti-inflammatory effects of S. scilloides bulbs for its traditional usage using lipoxygenase and hyaluronidase as the inflammation model. To gain insight into the active constituents, nine homoisoflavones (1-9) were subsequently tested. MATERIALS AND METHODS: Lipoxygenase and hyaluronidase inhibition of ethyl acetate extract from the bulbs of this plant within 2000 µg/mL or homoisoflavones within 1000 µM were determined by colorimetric methods. RAW264.7 cells were incubated with 10 or 50 µM homoisoflavones plus lipopolysaccharide (LPS) for 24 h. The culture media were collected and analyzed for determination of the nitric oxide (NO) level by the colorimetric Griess method to measure the extent of inflammation. RESULTS: The extract exhibited inhibitory effects on lipoxygenase and hyaluronidase activities with IC50 values 31.5 and 169 µg/mL, respectively. Among the nine homoisoflavones tested, four (1 and 3-5) resulted in 79.3-97.9% higher lipoxygenase inhibition than 6.7-32.7% of the others at 500 µM. Calculated IC50 values indicated 5 as the compound responsible for strong lipoxygenase inhibition with 15.8 µM as the IC50 value. In the hyaluronidase assay, all homoisoflavones tested at 1000 µM demonstrated 16.2-58.0% inhibition. Incubating the cells in the presence of all nine homoisoflavones tested at 50 µM significantly suppressed the NO production, downward to 1.5-66.0%, in the LPS-activated macrophage cells as a model. DISCUSSION AND CONCLUSION: These results may indicate a potential role of S. scilloides for anti-inflammatory purposes.

Isolation and structural characterization of eight new resin glycosides, calyhedins XVI-XXIII, from the rhizomes of Calystegia hederacea.

Biological effects attributed to resin glycosides, including cytotoxicity against cancer cells and antibacterial, multidrug resistance-modulating, and antiviral activities have been documented. Penta-glycosides composed of calysolic acid A or calyhedic acid A, which are glycosidic acid components of the crude resin glycoside fraction of Calystegia hederacea, have not yet been isolated from this plant. In this study, eight new resin glycosides, termed calyhedins XVI (1)-XXIII (8), were isolated from the rhizomes of C. hederacea. Compounds 1-8 are penta- or hexa-glycosides with macrolactone structures, and their sugar moieties are partially acylated by five organic acids, including 2S-methylbutyric, (E)-2-methylbut-2-enoic, and 2R-methyl-3R-hydroxybutyric acids. Compounds 1-5 are the first identified macrocyclic resin glycosides with five monosaccharides obtained from this plant, and 2 and 4 are the first to be characterized as containing calyhedic acid A as the glycosidic acid component. Compounds 1-8 were of the four following macrolactone types: one with a 22-membered ring (5), another with a 23-membered ring (6-8), the third with a 27-membered ring (1, 3), and the fourth with a 28-membered ring (2, 4). Compounds 2-8 exhibited cytotoxic activity against HL-60 human promyelocytic leukemia cells comparable to that of the positive control, cisplatin.

Identification and characterization of organic and glycosidic acids in the crude resin glycoside fraction of Ipomoea alba seeds.

Resin glycosides act as laxatives in crude drugs derived from plants of the Convolvulaceae family. These compounds have exhibited antibacterial, ionophoric, anti-inflammatory, antiviral, and multidrug resistance-modulating properties, as well as cytotoxicity against cancer cells. This study investigated the organic acid, hydroxyl fatty acid, monosaccharide, and glycosidic acid components of the crude resin glycoside fraction obtained from the methanol extract of Ipomoea alba L. (Convolvulaceae) seeds, which was subjected to alkaline and acidic hydrolysis. The alkaline hydrolysis yielded acetic, isobutyric, (E)-2-methylbut-2-enoic, and 2S-methyl-3S-hydroxybutyric acids as organic acid components, along with a glycosidic acid fraction. The acidic hydrolysis of the glycosidic acid fraction resulted in the isolation of 11S-hydroxytetradecanoic and 11S-hydroxyhexadecanoic acids as hydroxyl fatty acid components, as well as d-glucose, d-quinovose, d-fucose, d-xylose, and l-rhamnose as monosaccharide components. In addition, 10 new glycosidic acid methyl esters were isolated from the glycosidic acid fraction treated with trimethylsilyldiazomethane-hexane, along with one known glycosidic acid methyl ester. Of these, eight compounds contained new glycans. Four of these compounds were unusual natural glycosides with four glycosidic linkages to one monosaccharide. Their structures were determined using MS and NMR spectral analyses, which provided valuable insights into the unique glycosidic composition of I. alba seeds.

Eleven new glycosidic acid methyl esters from the crude resin glycoside fraction of Ipomoea alba seeds.

Resin glycosides are characteristic of plants of the Convolvulaceae family and are well-known purgative ingredients in crude drugs, such as Rhizoma Jalapae, Orizaba Jalapa Tuber, and Pharbitidis Semen, which are used in traditional medicine and derived from plants belonging to this family. Isolated resin glycosides have demonstrated diverse biological activities, including antibacterial, ionophoric, anti-inflammatory, antiviral, and multidrug-resistance-modulating properties, as well as cytotoxicity against cancer cells. These compounds consist of hydroxyl fatty acid oligoglycosides (glycosidic acids), with portions of the saccharide moieties acylated with some organic acids to form the core structure. This study investigated the glycosidic acid components of a crude resin glycoside fraction obtained from a methanolic extract of Ipomoea alba L. seeds (Convolvulaceae). Eleven new glycosidic acid methyl esters and one known methyl ester were isolated from a glycosidic acid fraction treated with trimethylsilyldiazomethane in hexane. Their structures were determined using acidic hydrolysis and electrospray ionization-time of fight mass spectrometry and NMR spectral analyses. These compounds are penta-, tetra-, or triglycosides, with methyl 11S-hydroxytetradecanoate or methyl 11S-hydroxyhexadecanoate as the aglycone. Although D-quinovose and L-rhamnose are common monosaccharide components, the remaining monosaccharides are D-glucose, D-xylose, or D-fucose. The crude resin glycoside fraction showed non-negligible cytotoxicity against HL-60 human promyelocytic leukemia cells.

Identification and characterization of organic and glycosidic acids in the crude resin glycoside fraction of Ipomoea lacunosa seeds.

Resin glycosides are commonly found in plants belonging to the Convolvulaceae family. Ipomoea lacunosa L. (Convolvulaceae) is an herbaceous vine native to the United States. The resin glycosides of this plant have not been studied in detail. In this study, the components of the crude resin glycoside fraction extracted from the seeds of I. lacunosa are characterized. Alkaline hydrolysis of the crude resin glycoside fraction obtained from methanolic extract of the seeds yielded three organic acids, namely, 2S-methylbutyric, (E)-2-methylbut-2-enoic, and 2R-methyl-3R-hydroxybutyric acids, and a glycosidic acid fraction. Acidic hydrolysis of the glycosidic acid fraction yielded hydroxyl fatty acid components, including 7S-hydroxydecanoic, 11S-hydroxytetradecanoic, 11S-hydroxyhexadecanoic, 3S,11S-dihydroxytetradecanoic, 3S,11S-dihydroxyhexadecanoic, and 3S,12S-dihydroxyhexadecanoic acids, as well as monosaccharide components, including d-glucose, d-quinovose, d-fucose, and l-rhamnose. Trimethylsilyldiazomethane-hexane treatment of the glycosidic acid fraction further yielded eleven previously undescribed glycosidic acid methyl esters and two known glycosidic acid methyl esters. The structures of the obtained compounds were characterized using various spectral techniques. Four of the undescribed compounds were hexaglycosides, five were heptaglycosides, and two were octaglycosides. The aglycone of these compounds was either methyl 11S-hydroxytetradecanoate, methyl 3S,11S-dihydroxytetradecanoate, or methyl 3S,11S-dihydroxyhexadecanoate. Among the undescribed compounds identified, eight contained novel glycans, and three were rare bisdesmosides with sugar linkages at the C-3 and C-11 positions of methyl 3S,11S-dihydroxytetradecanoate.

Four new resin glycosides from Ipomoea muricata seeds: muricatins XIV-XVII.

Ipomoea muricata (L.) Jacq. seeds (Convolvulaceae) are used as a traditional laxative and carminative medicine. Muricatins XIV (1), XV (2), XVI (3), and XVII (4), were isolated from I. muricata seeds as four new resin glycosides, along with seven known compounds, three of which were isolated for the first time as natural products; their structures were determined using MS and NMR spectroscopy. Compounds 1-4 are macrolactones (jalapins); the sugar moieties of 1, 2, and 4 are partially acylated with 2S-methylbutyric acid, while that of 3 is esterified with 2S-methylbutyric and 2S-methyl-3S-hydroxybutyric acids. In addition, the antiviral activities of the seven compounds obtained in this study, together with five known compounds obtained in our previous study into resin glycosides from I. muricata seeds, were evaluated against herpes simplex virus type 1 (HSV-1); their cytotoxicities against HL-60 human promyelocytic leukemia cells were also investigated. All examined jalapins exhibited similar or slightly weaker anti-HSV-1 activities than acyclovir, the positive control; however, the glycosidic acid of 4 was inactive, while its methyl ester was weakly active. On the other hand, cytotoxicity testing against HL-60 cells showed similar results to those observed during anti-HSV-1 activity testing, with the exception that one jalapin was less active.

Anti-inflammatory and antioxidative effects of a methanol extract from bulbs of Scilla scilloides.

The extract from bulbs of Scilla scilloides exhibited inhibitory effects in lipoxygenase and hyaluronidase assays and various oxidation models in vitro. Incubating the cells in the presence of this extract ameliorated t-butyl hydroperoxide-induced cytotoxicity from 27% to 57% in a macrophage model. The results may indicate the potential role of S. scilloides for its anti-inflammatory and antioxidative effects.

Irritable bowel syndrome, its cognition, anxiety sensitivity, and anticipatory anxiety in panic disorder patients.

AIM: The present study examined the effect of irritable bowel syndrome (IBS), cognitive appraisal of IBS, and anxiety sensitivity on anticipatory anxiety (AA) and agoraphobia (AG) in patients with panic disorder (PD). METHODS: We examined 244 PD patients who completed a set of questionnaires that included the Rome II Modular Questionnaire to assess the presence of IBS, the Anxiety Sensitivity Index (ASI), the Cognitive Appraisal Rating Scale (CARS; assessing the cognitive appraisal of abdominal symptoms in four dimensions: commitment, appraisal of effect, appraisal of threat, and controllability), and items about the severity of AA and AG. The Mini International Neuropsychiatric Interview was used to diagnose AG and PD. RESULTS: After excluding individuals with possible organic gastrointestinal diseases by using 'red flag items,' valid data were obtained from 174 participants, including 110 PD patients without IBS (PD/IBS[-]) and 64 with IBS (PD/IBS[+]). The PD/IBS[+] group had higher AA and higher comorbidity with AG than the PD/IBS[-] group. In the PD/IBS[+] group, the controllability score of CARS was significantly correlated with AA and ASI. Multiple regression analysis showed a significant effect of ASI but not of controllability on AA in PD/IBS[+] subjects. CONCLUSION: This study suggested that the presence of IBS may be related to agoraphobia and anticipatory anxiety in PD patients. Cognitive appraisal could be partly related to anticipatory anxiety in PD patients with IBS with anxiety sensitivity mediating this correlation.

Five new nortriterpenoid glycosides from the bulbs of Scilla scilloides.

Five new norlanostane-type triterpenoid glycosides were isolated from the bulbs of Scilla scilloides DRUCE (Liliaceae). Their chemical structures were determined on the basis of spectroscopic data as well as chemical evidence.