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Obesity is one of the major health problems which could trigger the development of many other non-communicable diseases. Tamarind (Tamarindus indica) is a multi-purpose plant that provides many health benefits, including anti-obesity potentials. In Indonesia, it is often used as a traditional food component in many dishes. A recent in vivo study proved that tamarind might reduce the bodyweight of obese rats. To further investigate the anti-obesity effect of tamarind, an in vitro study using 3T3-L1 pre-adipocytes was conducted. During differentiation, 3T3-L1 cells synthesize and accumulate lipid in the form of triglycerides in the cytoplasm. Tamarind water and ethanol extracts were incorporated into the medium during the differentiation stage of the cells. Oil red O staining assay was used to measure the total lipid accumulated. Results showed that both tamarind water and ethanol extracts exhibited non-cytotoxicity effects on 3T3-L1 cells. In addition, tamarind water extract at 10 mg/mL decreased the total lipid accumulated significantly to 80.5% compared with that of control, while tamarind ethanol extract showed less lipid accumulation inhibitory effect at any doses tested. This study revealed that tamarind water extract has the potential to reduce lipid accumulation, thus showing an anti-obesity effect.

We found thatp-synephrine inhibits the production of proinflammatory cytokines in LPS-stimulated RAW264.7 cells. This inhibitory effect could be attributed to the downregulation of p38 MAPK and NF-κB cascades mediated by β-adrenergic receptors.

Kampung-chicken, as a local wisdom, has always been considered superior in terms of health benefits compared to commercial chicken. Therefore, this study was designed to evaluate the immunostimulatory effects of Kampung-chicken eggs using in vitro approaches. The physical (interior and exterior quality) and chemical characteristics of Kampung-chicken eggs were firstly analyzed; the commercial chicken egg was used as a comparison. The effects of water extract of Kampung-chicken egg yolk (KEYWE) and water extract of commercial-chicken egg yolk (CEYWE) on IgM production and the expression of IgM-gene on HB4C5 cells were analyzed. In addition, the stimulatory effects of both samples on IgA, IgG, and IgM production by mouse primary splenocytes were analyzed as well. To isolate the active substance, the water extract from egg yolk was partially purified by salting out using (NH4)2SO4. Data analysis of the comparison between Kampung-chicken egg and the commercial-chicken egg was performed by t-test; meanwhile, the results for in vitro studies were performed by one-way ANOVA, and Tukey’s multiple comparison test was used for posthoc analysis. The result showed that KEYWE increased IgM production in HB4C5 cells by 5.91 fold as compared with control. In addition, KEYWE increased IgA, IgG, and IgM productions in mouse primary splenocytes by 5.20, 2.54, and 3.1 fold, respectively. Moreover, the immunoglobulin (Ig) production-stimulating activities of KEYWE on HB4C5 cells and mouse primary splenocytes were higher than those of CEYWE. The active substance in Kampung-chicken egg yolk was precipitated at 80% saturation of (NH4)2SO4. Altogether, it is expected that the Kampung-chicken egg has more effective immunostimulatory activity than the commercial chicken egg.

Coriander (Coriandrum sativum L.) is classified in the Apiaceae family and used as an herb. Coriander leaf has been reported to possess various health functions. Here, we report the anti-allergic effect of aqueous coriander leaf extract (ACLE). ACLE with 1.0 mg/mL or higher concentration significantly inhibited degranulation of RBL-2H3 cells in a concentration-dependent manner with no cytotoxicity. ACLE suppressed the increase in the intracellular Ca2+ concentration in response to antigen-specific stimulation. Immunoblot analysis demonstrated that ACLE significantly downregulates phosphorylation of phosphatidylinositol 3-kinase and tends to downregulate phosphorylation of Syk kinase in the signaling pathways activated by antigen-mediated stimulation. Oral administration of ACLE did not alter the sneezing frequency of pollinosis model mice stimulated with cedar pollen, but significantly reduced the serum IgE level. Our data show anti-allergic effects of coriander leaf in both cultured cells and pollinosis mice. These results suggest that coriander leaf has the potential to be a functional foodstuff with anti-allergy effects.

We found that a water-soluble extract of coriander (Coriandrum sativum L.) (leaves, petioles and stems) inhibits antigen-induced degranulation of RBL-2H3 cells, a rat basophil leukemia cell line. The aim of this study was to elucidate the anti-degranulation active components in the extract. The methanol-eluate fraction obtained by fractionation of the water-soluble extract using MCI gel column chromatography had strong activity, and eight components were isolated and identified. Two of them were identified as new compounds, (3S)-3-methyl-6-hydroxyisocoumarin 8-O-β-D-glucopyranoside (compound 1) and (7S,8R)-7,8-dihydro-8-β-D-glucopyranosyloxy-4-methoxy-7-methyl-5H-fro[2,3-g][2]benzopyran-5-one (compound 2). As a result of evaluation of anti-degranulation activity of eight components, seven of them, such as tryptophan, phenylalanine, dihydroxycoumarin glucoside, quercetin glycoside, rutin, compound 1, and compound 2, had the activity. These results indicated that the water-soluble extract of coriander contains several anti-degranulation substances.

Allergy rhinitis (AR), as reported by the World Allergy Organization (WAO), is one of the highest prevalence allergies affecting 10-30% of all adults and up to 40% of children. In Indonesia, current evidence showed that the prevalence of AR is increasing. Averrhoa bilimbi Linn. fruit (AF), or locally known as belimbing wuluh, has been scientifically proven to treat many diseases due to the abundant of polyphenol content which was shown to have the potential to treat allergies. Therefore, this study was aimed to investigate the anti-allergy potential of AF in vitro. The anti-allergy effect of Averrhoa bilimbi Linn. fruit water extract (AFWE) was examined using RBL-2H3 cells. At first, the cytotoxicity effect of AFWE was determined by WST-8 assay. The release of β-hexosaminidase by RBL-2H3 cells was also measured to evaluate degranulation suppression activity of AFWE. Lastly, calcium assay was employed to investigate the intracellular calcium concentration ([Ca­2+]i). Results demonstrated that AFWE does not show any cytotoxicity at any given concentration. In addition, AFWE at 1.25 mg/mL showed sufficient inhibitory effect towards degranulation by RBL-2H3 cells. Moreover, the degranulation-suppressing activity of AFWE was resulted from the inhibition of calcium-dependent signaling pathways. Unfortunately, the properties of active substances from AFWE have not been investigated. To conclude, this study indicated that AFWE has potential as an alternative treatment for allergic diseases.

Inflammation is related to various life-threatening diseases including cancer, neurodegenerative diseases, and metabolic syndrome. Because macrophages are prominent inflammatory cells, regulation of macrophage activation is a key issue to control the onset of inflammation-associated diseases. In this study, we aimed to evaluate the potential anti-inflammatory activity of Citrus unshiu leaf extract (CLE) and to elucidate the mechanism underlying its anti-inflammatory effect. We found the inhibitory activity of CLE on the secretion of proinflammatory cytokines and a chemokine from mouse macrophage-like RAW 264.7 cells and mouse peritoneal macrophages. The inhibitory activity of CLE was attributed to downregulated JNK, p38 MAPK, and NF-κB signaling pathways, leading to suppressed gene expression of inflammation-associated proteins. Oral administration of CLE significantly decreased the serum level of proinflammatory cytokines IL-6 and TNFα and increased that of anti-inflammatory cytokine IL-10 in lipopolysaccharide-induced systemic inflammation mice. In addition, oral administration of CLE decreased secretion and gene expression of several proinflammatory proteins in the liver and spleen of the model mice. Overall results revealed that C. unshiu leaf is effective to attenuate inflammatory responses in vitro and in vivo.

Coriandrum sativum L. seed is generally used as a spice and crude drug. Although many functions of the various components in C. sativum L. seed have been reported, the immunostimulatory effect of water-soluble components in C. sativum L. seed has not been studied. In the present study, we focused on the immunostimulatory effect of C. sativum L. seed aqueous extract (CAE) on macrophages as a novel health function of C. sativum L. seed components.; Results: CAE significantly enhanced the production of tumor necrosis factor (TNF)-α and interleukin (IL)-6 in both RAW264.7 cells and peritoneal macrophages by enhancing the expression levels of these cytokine genes. CAE also stimulated nitric oxide (NO) production and the phagocytosis activity in RAW264.7 cells. We suggest that the activity of CAE is a result of the upregulation of mitogen-activated protein kinase and nuclear factor-κB cascades via TLR4. In addition, IL-6 production by peritoneal macrophages collected from CAE-administered mice was significantly enhanced, suggesting that CAE could stimulate macrophage activity in vivo.; Conclusion: The findings of the present study suggest that CAE contains a novel water-soluble component with an immunostimulatory effect on macrophages. CAE would contribute to activating host defense against pathogens by stimulating the innate immunity. © 2017 Society of Chemical Industry.; © 2017 Society of Chemical Industry.

An array of foodstuffs was screened for the suppressive effect on production of IgE, a key molecule in the type I allergic reaction, using U266 cells. An ethanol extract from passion fruit seeds (PFS) has emerged as a food material with the IgE production-suppressive effect as the result of screening. Real-time RT-PCR analysis revealed that the IgE production-suppressive effect was caused by downregulated IgE gene expression. In addition, PFS selectively suppressed IgE production and did not affect the production of IgG, IgA, or IgM by mouse splenocytes. Resveratrol and piceatannol were identified as bioactive ingredients contained in passion fruit seeds. The effect of oral administration of PFS, resveratrol, and piceatannol was evaluated using a mouse model of allergic contact dermatitis. Both stilbenoids significantly suppressed IgE production in orally administered mice. Overall results indicated that passion fruit seeds are a promising candidate with the antiallergy effect for development of functional foods.

Dried bonito is a preserved food used in Japan, which contains abundant flavor ingredients and functional substances. We focused on the immunostimulatory effect of dried bonito extract (DBE) on mouse macrophage-like J774.1 cells, RAW264.7 cells, and mouse primary peritoneal macrophages. DBE significantly stimulated the production of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) by both J774.1 cells and peritoneal macrophages by enhancing the cytokine gene expression levels. In addition, DBE stimulated nitric oxide production by enhancing the expression of inducible nitric oxide synthase in RAW264.7 cells. DBE also increased the phagocytosis activity of J774.1 cells. Immunoblot analysis revealed that DBE has an immunostimulatory effect on macrophages through activation of mitogen-activated protein kinase and nuclear factor-κB cascades. TNF-α production enhanced by DBE was partially inhibited by treatment with TLR4 inhibitor TAK-242, whereas IL-6 production enhanced by DBE was almost inhibited. These results suggested that DBE is thought to strongly stimulate the TLR4 signaling pathway for macrophage activation, and its activation is also involved in other signaling. Finally, the phagocytosis activity of peritoneal macrophages from DBE-administered BALB/c mice increased significantly, suggesting that DBE has the potential to stimulate macrophage activity in vivo. In conclusion, these data indicated that DBE contributes to activating host defense against pathogens by activating innate immunity.

Trigonelline, one of the alkaloids contained in coffee, is important not only as one of the constituents of aroma and flavor in coffee but also as a useful source of nutrition. Its anti-microbial, anti-carcinogenic, and anti-hyperglycemic effects have been investigated in previous studies. However, there have not been any studies examining the anti-degranulation effect of trigonelline. In this study, the anti-degranulation effect of trigonelline was evaluated in in vitro and in vivo models using a rat basophilic leukemia cell line, RBL-2H3 cells, and a passive cutaneous anaphylaxis (PCA) reaction in mice, respectively. In the β-hexosaminidase release assay, trigonelline effectively suppressed antigen-induced degranulation of RBL-2H3 cells in a dose-dependent manner without cytotoxicity. Trigonelline also inhibited FceRI-mediated intracellular signaling pathways, such as phosphorylation of PLCγ1, PI3 K, and Akt, in antigen-stimulated RBL-2H3 cells and suppressed the PCA response in mice. Moreover, trigonelline also inhibited the microtubule formation in RBL-2H3 cells, indicating that trigonelline could inhibit IgE-sensitized mast cell degranulation by attenuating both the intracellular calcium-dependent and independent pathways. These results revealed that trigonelline possesses the anti-degranulation effect against the development of allergic diseases.

Kawachi-bankan (Citrus maxima) is one of the citruses produced in Ehime, Japan. Although health functions of flavonoids and carotenoids in citrus peel have been studied very well, those of water-soluble substances in the peel have not been focused. We herein indicated the anti-inflammatory effect of Kawachi-bankan peel aqueous extract (KPE) in vitro and in vivo. KPE significantly inhibited the production of inflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor (TNF)-α by LPS-stimulated RAW264.7 cells without cytotoxicity. KPE also significantly inhibited the mRNA expression levels of IL-6 and TNF-α in the cells, suggesting that KPE inhibits the production of inflammatory cytokines by suppressing the gene expression levels. Immunoblot analysis revealed that KPE shows an anti-inflammatory effect on macrophages through the suppression of the phosphorylation of p38 and the translocation of NF-κB into nucleus. The oral administration of KPE inhibited the serum levels of inflammatory cytokines and improved the survival rate in systemic inflammatory response syndrome (SIRS) model mice. Our experiments using a cell line suggested that KPE inhibits the production of inflammatory cytokines by macrophages in hyperinflammatory state. In addition, experiments in vivo showed that the oral administration of KPE inhibited the serum levels of inflammatory cytokines and improved the survival rate in SIRS model mice. Our findings indicated that KPE contributes to alleviating of a hyperinflammatory response.

Cuminum cyminum L. (cumin) seed is used as a spice in various countries. Although several functions of the components in cumin seed have been reported, the anti-allergic effect of the water-soluble component in cumin seed has not been reported yet. In this study, we focused on the suppressive effect of cumin seed aqueous extract on degranulation in order to reveal the anti-allergic effect of cumin. Cumin seed aqueous extract significantly suppressed the antigen-induced degranulation of rat basophilic leukemia cell line RBL-2H3 cells in a dose-dependent manner without cytotoxicity. The extract also inhibited the elevation of the intracellular calcium ion concentration induced by antigen. Immunoblot analysis revealed that the extract suppresses phosphorylation of phosphatidylinositol 3-kinase, Bruton’s tyrosine kinase, phospholipase C-γ1/2, and Akt in the signaling pathways activated by antigen induction via FcεRI. Furthermore, the extract suppressed microtubule formation induced by antigen. In addition, oral administration of cumin seed aqueous extract significantly suppressed the passive cutaneous anaphylaxis reaction in BALB/c mice. Our findings suggest that cumin seed contains water-soluble components with the anti-allergic effect. Therefore, cumin seed has potential as anti-allergic functional food. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10616-019-00309-2) contains supplementary material, which is available to authorized users.

We herein report the immunostimulatory effect of spinach aqueous extract (SAE) on mouse macrophage-like J774.1 cells and mouse primary peritoneal macrophages. SAE significantly enhanced the production of interleukin (IL)-6 and tumor necrosis factor-α by both J774.1 cells and peritoneal macrophages by enhancing the expression levels of these cytokine genes. In addition, the phagocytosis activity of J774.1 cells was facilitated by SAE. Immunoblot analysis revealed that SAE activates mitogen-activated protein kinase and nuclear factor-κB cascades. It was found that SAE activates macrophages through not only TLR4, but also other receptors. The production of IL-6 was significantly enhanced by peritoneal macrophages from SAE-administered BALB/c mice, suggesting that SAE has a potential to stimulate macrophage activity in vivo. Taken together, these data indicate that SAE would be a beneficial functional food with immunostimulatory effects on macrophages.

Immunoglobulin E (IgE) is involved in the onset of allergic reaction, and the suppression of IgE production leads to alleviation of allergic symptoms. We found that mango peel ethanol extract (MPE) significantly suppresses IgE production by human myeloma cell line U266 cells, suggesting that MPE has an anti-allergic effect by inhibiting the production of IgE. Although mangiferin is contained in mango, which suppresses IgE production by U266 cells, it was not contained in MPE. We investigated the suppressive effect of MPE in 2,4-dinitrofluorobenzene (DNFB)-induced allergic contact dermatitis model mice. The elevation of serum IgE level was significantly suppressed by oral administration of MPE. Intake of MPE also suppressed the expression level of IL-4 in the DNFB-challenged ears, suggesting that MPE suppresses the IL-4-mediated maturation into IgE-producing cells. Our findings indicate that MPE has a potential to alleviate the increase in serum IgE level that is feature of type I allergy.

Chlorophyll c2 in a Sargassum horneri extract suppressed the degranulation of rat basophilic leukaemia RBL-2H3 cells. In this contribution, the mode of action of S. horneri extract was revealed. The extract inhibited the elevation of intracellular Ca 2+ concentration induced by the antigen. Immunoblot analysis showed that S. horneri extract down-regulated the phosphorylation of both Syk and PI3K in the signalling pathways involved in degranulation triggered by antigen–antibody interaction. In addition, oral administration of S. horneri extract inhibited mice nasal rubbing behaviour sensitized with anti-DNP IgE. These findings suggest that S. horneri extract has anti-allergic activity via the suppression of degranulation of mast cells and basophils.

Based on some studies, moderate caffeine consumption provides several benefits to human health. However, there are few reports on the anti-degranulation activity of caffeine. Allergy is a global healthcare problem that is drastically increasing in both developed and developing countries. Meanwhile, allergic reactions are triggered by the presence of chemical mediators released from the granules in mast cells, which are called the degranulation process. In this study, caffeine was evaluated for anti-degranulation activity using basophilic cell line RBL-2H3 cells as the in vitro model and the passive cutaneous anaphylaxis (PCA) model mice in vivo. As a result, caffeine effectively suppressed antigen-induced degranulation by RBL-2H3 cells in a dose-dependent manner without cytotoxicity. Besides, caffeine also inhibited FceRI-mediated intracellular signaling pathways, such as phosphorylation of Syk, Btk, PLCγ1, PI3K, and Akt in antigen-stimulated RBL-2H3 cells. Caffeine also suppressed PCA response in mice.

The inhibitory effect of an aqueous extract from spinach on degranulation of RBL-2H3 cells is herein reported. The extract significantly suppressed antigen-induced degranulation in a dose-dependent manner without affecting cell viability. Active substances in the extract were heat-stable and trypsin-resistant with molecular weights ranging from 500 Da to 14 kDa. The extract inhibited elevation of the intracellular Ca(2+) concentration caused by stimulation by antigen, while not suppressing degranulation induced by a calcium ionophore A23187. Immunoblot analysis revealed that the inhibitory effect results from downregulation of phosphorylation of both Syk kinase and phosphatidylinositol 3-kinase in the signalling pathways involved in degranulation caused by the antigen-antibody interaction. Taken together, these findings suggest that aqueous spinach extract has an anti-allergic activity that controls degranulation.

Coriandrum sativum L. seed is generally used as a spice and crude drug. Although many functions of the various components in C. sativum L. seed have been reported, the immunostimulatory effect of water-soluble components in C. sativum L. seed has not been studied. In the present study, we focused on the immunostimulatory effect of C. sativum L. seed aqueous extract (CAE) on macrophages as a novel health function of C. sativum L. seed components.CAE significantly enhanced the production of tumor necrosis factor (TNF)-α and interleukin (IL)-6 in both RAW264.7 cells and peritoneal macrophages by enhancing the expression levels of these cytokine genes. CAE also stimulated nitric oxide (NO) production and the phagocytosis activity in RAW264.7 cells. We suggest that the activity of CAE is a result of the upregulation of mitogen-activated protein kinase and nuclear factor-κB cascades via TLR4. In addition, IL-6 production by peritoneal macrophages collected from CAE-administered mice was significantly enhanced, suggesting that CAE could stimulate macrophage activity in vivo.The findings of the present study suggest that CAE contains a novel water-soluble component with an immunostimulatory effect on macrophages. CAE would contribute to activating host defense against pathogens by stimulating the innate immunity. © 2017 Society of Chemical Industry.