Potential for tyndalized Lactobacillus acidophilus as an effective component in moisturizing skin and anti-wrinkle products.

It is widely accepted that ultraviolet (UV) irradiation induces skin damage. In the present study, a UVB-induced hairless mouse model of skin photoaging was developed to determine whether tyndalized Lactobacillus acidophilus was able to significantly enhance the repair of photodamaged skin. To evaluate the effects of tyndalized L. acidophilus on UVB-induced skin-wrinkle formation in vivo, HR-1 hairless male mice were exposed to UVB radiation and orally administered tyndalized L. acidophilus. Compared with the control group, the UVB irradiation mice displayed a significant increase in transepidermal water loss and a reduction in skin hydration. In mice with UVB-induced photodamage, the effacement of the fine wrinkles by tyndalized L. acidophilus was correlated with dermal collagen synthesis, accompanied by histological changes. Furthermore, western blotting was performed to investigate the protein expression levels of matrix metalloproteinases (MMPs) and mitogen-activated protein kinase. Notably, orally administered tyndalized L. acidophilus reduced the expression levels of MMP-1 and MMP-9. Based upon the aforementioned results, it was determined that tyndalized L. acidophilus effectively inhibited the wrinkle formation induced by UVB irradiation, and that this may be attributed to the downregulation of MMPs. Therefore, tyndalized L. acidophilus may be considered a potential agent for preventing skin photoaging and wrinkle formation.

Phenylacylphenol derivatives with anti-melanogenic activity from Stewartia pseudocamellia.

Three new phenylacylphenol derivatives, stewartianol (1), deoxystewartianol-4'-O-arabinoglucoside (2), and stewartianol-3-O-glucoside (3), along with nine known compounds, methylesculin (4), fraxoside (5), fraxetin (6), scopletin (7), (+)-dihydromyricetin (8), (+)-taxifolin-7-O-ß-D-glucose (9), (+)-taxifolin (10), (+)-dihydrokaempferol-7-O-ß-D-glucose (11), and 3-acetyl-ursolic acid (12), were isolated from the twigs of Stewartia pseudocamellia; commonly used as folk medicine in Korea. The structures of the isolated compounds were identified using spectroscopic analysis, including 1D, 2D NMR, MS and compared with published data. The compounds were tested for their anti-melanogenic activity in cultured murine B16 melanoma cells. Stewartianol (1) and stewartianol-3-O-glucoside (3) showed an inhibitory effect significantly on melanogenesis in a concentration-dependent manner.

Verproside inhibits TNF-α-induced MUC5AC expression through suppression of the TNF-α/NF-κB pathway in human airway epithelial cells.

Airway mucus secretion is an essential innate immune response for host protection. However, overproduction and hypersecretion of mucus, mainly composed of MUC5AC, are significant risk factors in asthma and chronic obstructive pulmonary disease (COPD) patients. Previously, we reported that verproside, a catalpol derivative iridoid glycoside isolated from Pseudolysimachion rotundum var. subintegrum, is a potent anti-asthmatic candidate drug in vivo. However, the molecular mechanisms underlying the pharmacological actions of verproside remain unknown. Here, we found that verproside significantly reduces the expression levels of tumor necrosis factor alpha (TNF-α)-induced MUC5AC mRNA and protein by inhibiting both nuclear factor kappa B (NF-κB) transcriptional activity and the phosphorylation of its upstream effectors such as IκB kinase (IKK)ß, IκBα, and TGF-ß-activated kinase 1 (TAK1) in NCI-H292 cells. Moreover, verproside attenuated TNF-α-induced MUC5AC transcription more effectively when combined with an IKK (BAY11-7082) or a TAK1 (5z-7-oxozeaenol) inhibitor than when administered alone. Importantly, we demonstrated that verproside negatively modulates the formation of the TNF-α-receptor (TNFR) 1 signaling complex [TNF-RSC; TNFR1-recruited TNFR1-associated death domain protein (TRADD), TNFR-associated factor 2 (TRAF2), receptor-interacting protein kinase 1 (RIP1), and TAK1], the most upstream signaling factor of NF-κB signaling. In silico molecular docking studies show that verproside binds between TRADD and TRAF2 subunits. Altogether, these results suggest that verproside could be a good therapeutic candidate for treatment of inflammatory airway diseases such as asthma and COPD by blocking the TNF-α/NF-κB signaling pathway.

Thuja orientalis reduces airway inflammation in ovalbumin-induced allergic asthma.

Thuja orientalis (TO) may be used as a herbal remedy for the treatment of numerous inflammatory diseases. In the present study, the effects of TO were evaluated on airway inflammation in ovalbumin (OVA)­induced allergic asthma and RAW264.7 murine macrophage cells. The effects of TO on the production of proinflammatory mediators, were determined in RAW264.7 cells that had been stimulated with lipopolysaccharide (LPS). Furthermore, an in vivo experiment was performed on mice that were sensitized to OVA and then received an OVA airway challenge. TO was administered by daily oral gavage at a dose of 30 mg/kg, 21­23 days after the initial OVA sensitization. TO was shown to reduce nitric oxide production and reduce the relative mRNA expression levels of inducible nitric oxide synthase (iNOS), interleukin (IL)­6, cyclooxygenase­2, matrix metalloproteinase (MMP)­9, and tumor necrosis factor­α in RAW264.7 cells stimulated with LPS. In addition, TO markedly decreased the inflammatory cell counts in bronchial alveolar lavage fluid, reduced the levels of IL­4, IL­5, IL­13, eotaxin and immunoglobulin E, and reduced airway hyperresponsivenes, in the OVA sensitized mice. Furthermore, TO attenuated airway inflammation and mucus hypersecretion, induced by the OVA challenge of the lung tissue. TO also reduced the expression of iNOS and MMP­9 in lung tissue. In conclusion, TO exerted anti­inflammatory effects in an OVA­induced allergic asthma model, and in LPS­stimulated RAW264.7 cells. These results suggest that TO may be a useful therapeutic agent for the treatment of inflammatory diseases, including allergic asthma.

Zingiber mioga (Thunb.) Roscoe attenuates allergic asthma induced by ovalbumin challenge.

Zingiber mioga (Thunb.) Roscoe (ZM) is a traditional medicine, used to treat inflammatory diseases. The present study aimed to evaluate the inhibitory effects of ZM on the inflammatory response in lipopolysaccharide (LPS)­stimulated RAW264.7 murine macrophage cells and in a mouse model of ovalbumin (OVA)­induced allergic asthma. Mice received OVA sensitization on day 0 and 14, and were challenged with OVA between days 21 and 23. ZM was administered to the mice at a dose of 30 mg/kg, 1 h prior to OVA challenge. In LPS­stimulated RAW264.7 cells, ZM significantly decreased nitric oxide (NO) and tumor necrosis factor (TNF)­α production in a concentration­dependent manner, and mRNA expression of inducible NO synthase (iNOS), TNF­α and matrix metalloproteinase (MMP)­9 was reduced. In addition, treatment with ZM decreased the inflammatory cell count in bronchoalveolar lavage fluid from the mice, and reduced the expression of interleukin (IL)­4, IL­5, IL­13, eotaxin and immunoglobulin E. ZM also reduced airway hyperresponsiveness in OVA­challenged mice, and attenuated the infiltration of inflammatory cells and mucus production in the airways, with a decrease in the expression of iNOS and MMP­9 in lung tissue. In conclusion, the results of the present study indicate that ZM effectively inhibits inflammatory responses. Therefore, it may be that ZM has potential as a therapeutic agent for use in inflammatory diseases.

Triterpene glycosides with stimulatory activity on melanogenesis from the aerial parts of Weigela subsessilis.

Three new triterpene glycosides (Lonicerosides K, L and M) and 11 known compounds were isolated from the aerial parts of Weigela subsessilis. Among the known isolated compounds, loniceroside A, sweroside, kaempferol-3-O-glucopyranoside 6″-(3-hydroxy-3-methylglutarate), kaempferol-3-O-acetylglucoside and grandifloroside were reported for the first time in a Weigela genus plant. Their chemical structures were identified using extensive spectroscopic analysis including two-dimensional (2D)-NMR experiments, HR-ESI-QTOF-MS and comparison with reported data. Among these compounds, lonicerosides A and L had potent melanogenesis stimulatory activity in murine B16F0 melanoma cells. The structural relationship of active compounds was discussed.

Siegesbeckia glabrescens attenuates allergic airway inflammation in LPS-stimulated RAW 264.7 cells and OVA induced asthma murine model.

Siegesbeckia glabrescens (SG) is a plant growing in Korea that is used as a traditional medicine for various inflammatory diseases. In this study, we investigated the protective effects of SG extract on allergic asthma in an ovalbumin (OVA)-induced asthma murine model and lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Female BALB/c mice were sensitized by intraperitoneal injection of OVA on days 0 and 14 and then challenged with OVA from days 21 to 23. SG (30mg/kg) was administered by oral gavage 1h before the OVA challenge. LPS-stimulated RAW264.7 cells were evaluated to determine their levels of nitric oxide (NO). The SG significantly reduced the number of inflammatory cells in bronchoalveolar lavage (BAL) fluid and also reduced IL-4, IL-5, IL-13, eotaxin and immunoglobulin E in OVA-sensitized/challenged mice. SG also effectively reduced airway inflammation and mucus overproduction in lung tissue in addition to decreasing the expression of iNOS and COX-2. In LPS-stimulated RAW264.7 cells, SG treatment significantly reduced the levels of NO. These findings indicate that SG effectively suppressed inflammatory responses, and its effects appear to be related to reduction in iNOS and COX-2 expression. Therefore, we suggest that SG may have potential use as a therapeutic agent for inflammatory diseases such as allergic asthma.

Melatonin inhibits MUC5AC production via suppression of MAPK signaling in human airway epithelial cells.

Mucus acts as a primary defense system in the airway against various stimuli. However, excess mucus production causes a reduction in lung function via limitation of the airflow in the airway of patients suffering from asthma or chronic obstructive pulmonary disease (COPD). In this study, we evaluated the effects of melatonin on the production of MUC5AC, a major constituent of the mucin that is secreted from the airway, using epidermal growth factor (EGF)-stimulated NCI-H292 cells, a human mucoepidermoid carcinoma cell line, and an ovalbumin (OVA)-induced asthma murine model. Melatonin treatment significantly reduced the mRNA and protein levels of MUC5AC and reduced interleukin (IL)-6 production in EGF-stimulated H292 cells. Melatonin markedly decreased the phosphorylation of MAPKs, including ERK1/2, JNK, and p-38, induced by EGF stimulation. These findings were consistent with the results using MAPK inhibitors. Particularly, co-treatment with melatonin and a MAPK inhibitor more effectively suppressed MAPK phosphorylation than treatment with a MAPK inhibitor alone, which resulted in a reduction in MUC5AC expression. In the asthma murine model, melatonin-treated mice exhibited a marked reduction in MUC5AC expression in the airway compared with the OVA-induced mice. These reductions were accompanied by reductions in proinflammatory cytokine production and inflammatory cell infiltration. Collectively, these findings indicate that melatonin effectively inhibits MUC5AC expression. These effects may be closely associated with the inhibition of MAPK phosphorylation. Furthermore, our study suggests that melatonin could represent a potential therapeutic for chronic airway diseases, such as asthma and COPD.

Anti-inflammatory activity of a methanol extract from Ardisia tinctoria on mouse macrophages and paw edema.

Ardisia tinctoria (AT) is a plant of the Myrsinaceae family. No studies on its anti-inflammatory effects have yet been reported. This study investigated the anti-inflammatory activity of AT. A non-cytotoxic methanol extract of AT inhibited the expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2), leading to significantly reduced levels of nitric oxide (NO) and prostaglandin E2 (PGE2) and of two proteins regulated by these, interleukin-1ß (IL-1ß) and IL-6, in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. The thickness of paw edema induced in vivo in mice by carrageenan administration was effectively reduced by the AT extract. Translocation of the nuclear factor-κB (NF-κB) subunit 65 (p65) into the nucleus and phosphorylation of mitogen-activated protein kinase kinase (MEK) and extracellular signal-related kinase (ERK) were inhibited by the AT extract. Our results indicated that a methanol extract of AT downregulates the inflammatory response by blocking phosphorylation of MEK and ERK and activation of NF-κB. To the best of our knowledge, this is the first study of anti-inflammatory effects of an AT extract, and demonstrates its potential in the treatment of inflammatory diseases.

Anti-inflammatory activities of methanol extract of Mastixia arborea C.B. Clarke as to mouse macrophage and paw edema.

The biological activity of Mastixia arborea (MA) relates to inflammation, but the underlying mechanisms are largely unknown. We confirmed the anti-inflammatory effects of a methanol extract of MA extract on lipopolysaccharide (LPS)-stimulated RAW264.7 mouse macrophage cells and carrageenan-induced mice paw edema. The MA extract significantly inhibited nitric oxide (NO), prostaglandin E2 (PGE2), interleukin-1ß (IL-1ß), and IL-6 production in LPS-stimulated RAW264.7 cells. In vitro expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) was suppressed by the extract. The extract attenuated acute inflammatory responses in carrageenan-induced mice paw edema. A mechanism study indicated that translocation of the NF-κB (p65) subunit into the nucleus and phosphorylation of ERK and JNK were inhibited by the extract. These results indicate that the extract is an effective suppressor of the inflammatory response, blocking the phosphorylation of ERK and JNK and the translocation of NF-κB in macrophages, thereby producing an anti-inflammatory effect in vivo.

Diallyl-disulfide, an organosulfur compound of garlic, attenuates airway inflammation via activation of the Nrf-2/HO-1 pathway and NF-kappaB suppression.

Diallyl disulfide (DADS) is a major organosulfur compound found in garlic oil that is widely used as a flavoring agent. In this study, we evaluated the effects of DADS on airway inflammation using an ovalbumin-induced model of allergic asthma and RAW264.7 cells. DADS decreased nitric oxide production with a reduction in the levels of interleukins (IL)-1ß and IL-6 in RAW264.7 cells stimulated with LPS. DADS also reduced the expression of proinflammatory proteins including inducible nitric oxide synthase (iNOS), nuclear factor (NF)-κB, and matrix metalloproteinase (MMP)-9, and it enhanced the expression of antioxidant proteins including Nrf-2 and hemeoxygenase (HO)-1. In in vivo experiments, DADS decreased the inflammatory cell count in the bronchoalveolar lavage fluid (BALF) with IL-4, IL-5, IL-13, and immunoglobulin (Ig) E. These results were consistent with the histological analysis. DADS attenuated the airway inflammation and mucus hypersecretion induced by OVA challenge. In addition, DADS induced the activation of Nrf-2 and the expression of HO-1. In contrast, DADS reduced the activation of NF-κB, iNOS and MMP-9. In conclusion, DADS reduced the airway inflammation via regulation of Nrf-2/HO-1 and NF-κB. These results suggest that DADS might represent a useful new oral therapy to treat allergic asthma.

Anti-human rhinoviral activity of polybromocatechol compounds isolated from the rhodophyta, Neorhodomela aculeata.

An extract of the red alga, Neorhodomela aculeata, exhibited antiviral activity against human rhinoviruses. Bioassay-guided purification was performed to yield six compounds, which were subsequently identified as lanosol (1) and five polybromocatechols (2-6) by spectroscopic methods, including 1D and 2D NMR and mass spectrometric analyses. Structurally, all of these compounds, except compound 5, contain one or two 2,3-dibromo-4,5-dihydroxyphenyl moieties. In a biological activity assay, compound 1 was found to possess antiviral activity with a 50% inhibitory concentration (IC50) of 2.50 µg/mL against HRV2. Compound 3 showed anti-HRV2 activity, with an IC50 of 7.11 µg/mL, and anti-HRV3 activity, with an IC50 of 4.69 µg/mL, without demonstrable cytotoxicity at a concentration of 20 µg/mL. Collectively, the results suggest that compounds 1 and 3 are candidates for novel therapeutics against two different groups of human rhinovirus.

Inhibition of UVB-induced wrinkle formation and MMP-9 expression by mangiferin isolated from Anemarrhena asphodeloides.

Chronic exposure of human skin to solar ultraviolet (UV) radiation causes photoaging. Naturally occurring phytochemicals are known to have anti-photoaging effects. The present study examined the effect of mangiferin isolated from Anemarrhena asphodeloides on wrinkle formation, skin thickness, and changes in collagen fibers in hairless mice. The in vitro effects and possible mechanism of mangiferin on UVB irradiation were determined in human keratinocyte (HEKa) cells. In vitro results showed that mangiferin reduced UVB-induced matrix metalloproteinase (MMP)-9 protein expression and enzyme activity and subsequent attenuation of UVB-induced phosphorylation of mitogen-activated protein kinase kinase1 (MEK) and extracellular signal-regulated kinase (ERK). In the in vivo studies, mangiferin inhibited UVB-induced mean length and mean depth of skin wrinkle based on skin replica, epidermal thickening, and damage to collagen fiber. Taken together, these results indicate that mangiferin exerts anti-photoaging activity in UVB-irradiated hairless mice by regulating MMP-9 expression through inhibition of MEK and ERK.

3-Deoxysappanchalcone inhibits tumor necrosis factor-α-induced matrix metalloproteinase-9 expression in human keratinocytes through activated protein-1 inhibition and nuclear factor-kappa B DNA binding activity.

Tumor necrosis factor α (TNF-α), which is a primary cytokine responsible for inflammatory responses in skin, induces the synthesis of matrix metalloproteinase-9 (MMP-9), which causes skin aging. The protective effects of 3-deoxysappanchalcone against TNF-α-induced damage was investigated using human skin keratinocytes. The results showed that 3-deoxysappanchalcone inhibited MMP-9 expression at the protein and mRNA level, by blocking the activation of activator protein-1 (AP-1) and nuclear factor kappa B (NF-κB). Taken together, the inhibitory activity of 3-deoxysappanchalcone on MMP-9 expression and production in TNF-α-treated cells was found to be mediated by the suppression of AP-1 and NF-κB activation.

Anti-inflammatory and anti-asthmatic effects of Viola mandshurica W. Becker (VM) ethanolic (EtOH) extract on airway inflammation in a mouse model of allergic asthma.

AIM OF THE STUDY: We investigated the efficacy of Viola mandshurica W. Becker (VM) ethanolic (EtOH) extract in the treatment of bronchial asthma in an ovalbumin (OVA)-induced asthmatic BALB/c mouse model. MATERIALS AND METHODS: Female BALB/c mice were sensitized with intraperitoneal (i.p.) ovalbumin (OVA) on days 0 and 14, and were next given intranasal OVA on days 28-30. Randomized treatment groups of sensitized mice received VM EtOH extract, dexamethasone, or placebo, orally, from days 28 to 30. RESULTS: VM EtOH extract significantly inhibited increases in total immunoglobulin E (IgE) and cytokines IL-4 and IL-13 levels in serum and bronchoalveolar lavage fluid (BALF), and also effectively suppressed airway hyperresponsiveness (AHR), eosinophilia, and mucus hypersecretion, in mice with OVA-induced asthma. CONCLUSIONS: The results suggest that VM EtOH extract and allied extracts could be useful herbal medicines for asthma treatment, and that VM may also be a valuable lead material for anti-asthma drug development.

Anti-inflammatory activity of (-)-aptosimon isolated from Daphne genkwa in RAW264.7 cells.

In the present study, we investigated that (-)-aptosimon, isolated from flower buds of Daphne genkwa, inhibited cyclooxygenase-2 (COX-2) and inducible nitric oxide (NO) synthase (iNOS) expression in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Similarly, (-)-aptosimon suppressed tumor necrosis factor (TNF)-alpha production. Our results clearly indicated that (-)-aptosimon inhibited LPS-induced nuclear factor-kappaB (NF-kappaB) activation, by preventing degradation of the inhibitor kappa B-alpha (IkappaB-alpha). (-)-Aptosimon also inhibited interleukin-4 (IL-4) and interleukin-13 (IL-13) production in ConA-induced splenocytes. In conclusion, the anti-inflammatory effects of (-)-aptosimon are attributed to the suppression of pro-inflammatory cytokines and mediators by blocking NF-kappaB activation. These data suggest that (-)-aptosimon as a potential therapeutic agent for inflammation-associated disorders.