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The normal inflammatory reaction protects the body from harmful external factors, whereas abnormal chronic inflammation can cause various diseases, including cancer. The purpose of the present study was to investigate the anti‑inflammatory activity of a mixture of Chrysanthemum zawadskii, peppermint and Glycyrrhiza glabra (CPG) by analyzing the expression levels of inflammatory mediators, cytokines and transcription factors in lipopolysaccharide (LPS)‑stimulated Raw264.7 cells. A nitric oxide assay, ELISA, western blotting and immunofluorescence staining were performed to investigate the anti‑inflammatory activity of the CPG mixture. Pretreatment of Raw264.7 cells with CPG inhibited the increase of inflammatory mediators (inducible nitric oxide synthase, cyclooxygenase‑2 and IFN‑β) induced by LPS. Additionally, it inhibited the production of pro‑inflammatory cytokines (TNF‑α, IL‑6 and IL‑1β). CPG suppressed LPS‑induced phosphorylation of STAT1, AKT, Iκb and NF‑κB. Furthermore, CPG inhibited the translocation of NF‑κB into the nucleus. In summary, CPG could inhibit LPS‑induced inflammation, which occurs primarily through the AKT/Iκb/NF‑κB signaling pathway in RAW264.7 cells.

Sophora flavescens, also known as Kushen, has traditionally been used as a herbal medicine. In the present study we evaluated the ameliorative effects of kushenol C (KC) from S. flavescens against tBHP (tert-Butyl hydroperoxide)-induced oxidative stress in hepatocellular carcinoma (HEPG2) cells and acetaminophen (APAP)-induced hepatotoxicity in mice. KC pretreatment protected the HEPG2 cells against oxidative stress by reducing cell death, apoptosis and reactive oxygen species (ROS) generation. KC pretreatment also upregulated pro-caspase 3 and GSH (glutathione) as well as expression of 8-Oxoguanine DNA Glycosylase (OGG1) in the HEPG2 cells. The mechanism of action was partly related by KC’s activation of Akt (Protein kinase B (PKB)) and Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) in the HepG2 cells. In in vivo investigations, coadministration of mice with KC and APAP significantly attenuated APAP-induced hepatotoxicity and liver damage, as the serum enzymatic activity of aspartate aminotransferase and alanine aminotransferase, as well as liver lipid peroxidation and cleaved caspase 3 expression, were reduced in APAP-treated mice. Coadministration with KC also up-regulated antioxidant enzyme expression and prevented the production of proinflammatory mediators in APAP-treated mice. Taken together, these results showed that KC treatment has potential as a therapeutic agent against liver injury through the suppression of oxidative stress.

Astrocytes release biologically active substances that cause inflammation in neurodegenerative diseases. The present study investigated the effects of two flavonoids (apigenin and luteolin) on the production of IL-31 and IL-33 in lipopolysaccharide (LPS)-activated astrocytes. Cell viability was investigated using EZ-Cytox assay, mRNA expressions of IL-31 and IL-33 were analyzed by RT-PCR, protein expressions were analyzed by western blot, and cytokine secretion was analyzed by ELISA. Apigenin and luteolin prevented astrocyte activation and inhibited mRNA and protein expression and secretion of IL-31 and IL-33 in the LPS-treated astrocytes. Apigenin's suppression of ERK, NF-κB, and STAT3 activations was responsible for the inhibition of IL-31 and IL-33, while luteolin's suppression of JNK, p38, ERK, NF-κB, and STAT3 activations was responsible for the inhibition of IL-31 in the astrocytes. Also, luteolin's suppression of ERK, NF-κB, and STAT3 activations inhibited IL-33 production in the activated astrocytes. In addition, apigenin and luteolin also prevented the translocation of activated STAT3 and NF-κB to the nucleus of the activated astrocytes and subsequently affected their DNA binding activities. The results suggest that apigenin and luteolin may have potentials as neuroprotective agents for the treatment of diseases involving astrocyte activation and detrimental production of IL-31 and IL-33.

Microglia cells are resident cells of the central nervous system (CNS) charged with modulating inflammation in the CNS. Overstimulation of microglia cells continuously releases inflammatory mediators that contribute to neurodegenerative diseases. Apigenin and Luteolin are flavonoids with reported anti-inflammatory activities. However, their effects on IL-31 and IL-33 production in microglial cells are unknown. Here, we investigated the effects of apigenin and luteolin on the production of IL-31 and IL-33 by microglia cells. SIM-A9 microglial cells were pre-treated with apigenin or luteolin and stimulated with lipopolysaccharides to evaluate the production of IL-31 and IL-33. The study revealed that apigenin and luteolin inhibited the production of IL-31 and IL-33 at the gene and protein expressions and the secretion levels. Using potent inhibitors of MAPK, NF-&kappa, B, and STAT3 signaling pathways, we demonstrated that apigenin and luteolin&rsquo, s suppression of ERK and JNK contributed to the inhibition of IL-31 and IL-33 in the MAPK pathway. Luteolin&rsquo, s suppression of NF-&kappa, B and STAT3 also contributed to the inhibition of IL-31 and IL-33. Further analysis revealed that both compounds prevented nuclear translocation of activated NF-&kappa, B and STAT3, an act that subsequently prevented their DNA binding activities. Collectively, the study suggested that apigenin and luteolin&rsquo, s regulation of signaling pathways contributed to the inhibition of IL-31 and IL-33, thus suggesting its importance for the improvement of neurodegenerative diseases involving these two cytokines.

Interleukin-31 (IL-31) is a recently discovered cytokine that is tightly linked to the pathogenesis of pruritus seen in atopic dermatitis. Flavonoids, like fisetin, are naturally occurring molecules with antioxidant, cytoprotective, and anti-inflammatory actions. Aim: the present study sought to investigate whether fisetin modulates IL-31 and histamine release in human mast cells (HMC-1). Main methods: HMC-1 cells were pretreated with fisetin at various doses and stimulated with phorbol-12-myristate 13-acetate and calcium ionophore A23187 (PI) for different time intervals. We evaluated IL-31 production and histamine release and signaling mechanism of the action of fisetin on IL-31 production. We also investigated the effects of fisetin on scratching behaviors in mice. Key findings: Fisetin decreased PI-stimulated mRNA expression and production of IL-31 in HMC-1 cells. Fisetin inhibited PI-induced phosphorylation of mitogen-activated protein kinases that further suppressed nuclear factor (NF-κB) activation and translocation to the nucleus through the inhibition of IκB-α phosphorylation. Fisetin also prevented mast cell release of histamine in HMC-1 cells. Mice in-vivo studies show that fisetin reduced scratching behaviors in mice. Significance: These pharmacological actions of fisetin provide new suggestions that fisetin can be of potential use for the treatment of pruritus that cannot be treated with histamine receptor blockers alone.

The aim of this study was to investigate the protective effect of Diospyros lotus leaf extract (DLE) on UVB-induced skin damage in mice. UVB irradiation of mice skin incurred significant damage to mice skin; increased thiobarbituric acid-reactive substance level; decreased superoxide dismutase; and glutathione levels in mice skin tissues. More so, UVB irradiation led to collagen degradation and infiltration of mast cell and neutrophils into mice skin leading to inflammation. However, topical application of DLE significantly reversed these conditions with the result comparable to l-ascorbic acid. Myricitrin, gallic acid, astragalin, myricetin-3-O-glactosside, and myricetin through high-performance liquid chromatography analysis were further determined to be the primary active compounds in DLE. In conclusion, our study showed that DLE has potentials as local therapeutic materials against skin damage by inhibiting oxidative stress and UVB-induced skin damage.

Humans have become exposed to another form of a trait which is ultraviolet B (UVB) radiation reaching the earth's surface. This has become a major source of oxidative stress that ultimately leads to inflammation, DNA damage, photoaging and pigmentation disorders etc. Although several studies have shown the photo-protective role of different grape parts like the fruits and seeds, little or no data demonstrating the in vivo photo-protective role of grape stem, which is the most discarded part of the grape are available. We evaluated the protective influence of grape stem extract against UVB-induced oxidative damage in C57BL mice characterized by epidermal hyperplasia, pigmentation, collagen degradation and inflammation. Grape stem extract was administered topically 1week before UVB irradiation (120mJ/cm2) and continued until the termination of the experiment. A group of non-irradiated mice and a group of irradiated mice topically administered with propylene were used as a negative and positive control. Epidermal thickness, pigmentation, erythema, mast cell and neutrophil infiltration, collagen degradation and COX-2, Nrf2, and HO-1 expressions were evaluated. Grape stem extract markedly recovered skin damage induced by the UVB radiation through the prevention of epidermal hyperplasia, pigmentation, erythema, mast cell and neutrophil infiltrations, collagen degradation and COX-2, Nrf2, and HO-1 expressions. Our study demonstrated for the first time in C57BL mice that grape stem extract reduces UVB-induced oxidative damage and hence can play a protective role in skin photo-damage.

Atopic dermatitis, a chronic relapsing and pruritic inflammation of the skin also thought to be involved in, or caused by immune system destruction is an upsetting health problem due to its continuously increasing incidence especially in developed countries. Mast cell infiltration in atopic dermatitis skin lesions and its IgE-mediated activation releases various cytokines and chemokines that have been implicated in the pathogenesis of atopic dermatitis. This study was aimed at investigating synergistic anti-inflammatory, anti-pruritic and anti-atopic dermatitis effects of Diospyros lotus leaf extract (DLE) and Muscat bailey A grapefruit stem extract (GFSE) in atopic dermatitis-like induced skin lesions in mice. Combinations of DLE and GFSE inhibited TNF-α and IL-6 production more than DLE or GFSE in PMA plus calcium ionophore A23187-activated HMC-1 cells. DLE and GFSE synergistically inhibited compound 48/80-induced dermal infiltration of mast cells and reduced scratching behavior than DLE or GFSE. Furthermore, DLE and GFSE synergistically showed a stronger ameliorative effect in skin lesions by reducing clinical scores; dermal infiltration of mast cells; ear and dorsal skin thickness; serum IgE and IL-4 production in atopic dermatitis-like mice. Collectively, these results suggest that DLE and GFSE synergistically exhibit anti-atopic dermatitis effects in atopic dermatitis-like skin lesions in mice.

The aim of this study was to compare the anti-oxidative and anti-inflammatory activities of gamma-irradiated persimmon leaf extract (GPLE) with those of non-irradiated persimmon leaf extract (PLE). Ethanolic extract of persimmon leaf was exposed to gamma irradiation at a dose of 10 kGy. After gamma irradiation, the color of the extract changed from dark brown to light brown. The anti-oxidative and anti-inflammatory activities of GPLE and PLE were assessed from: total polyphenol and total flavonoid contents; 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay; 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) assay, and levels of pro-inflammatory mediators such as nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6). The total polyphenol contents of GPLE and PLE were determined to be 224.44 ± 1.54 and 197.33 ± 5.81 mg gallic acid equivalents (GAE)/g, respectively, and the total flavonoid contents of GPLE and PLE were 206.27 ± 1.15 and 167.60 ± 2.00 mg quercetin equivalents (QUE)/g, respectively. The anti-oxidant activities of GPLE and PLE as measured by DPPH assays were 338.33 ± 30.19 μg/ml (IC50) and 388.68 ± 8.45 μg/ml (IC50), respectively, and those measured by ABTS assays were 510.49 ± 15.12 μg/ml (IC50) and 731.30 ± 10.63 μg/ml (IC50), respectively. IC50 is the inhibitor concentration that reduces the response by 50%. GPLE strongly inhibited the production of NO, PGE2 and IL-6 compared with PLE in lipopolysaccharide-stimulated RAW264.7 macrophages. Furthermore, GPLE significantly inhibited the production of TNF-α and IL-6 cytokines compared with PLE in phorbol 12-myristate 13-acetate (PMA) plus A23187-stimulated HMC-1 human mast cells. These results indicate that gamma irradiation of PLE can enhance its anti-oxidative and anti-inflammatory activities through elevation of the phenolic contents. Therefore, gamma-irradiated PLE has potential for use in the food and cosmetic industries.

This study investigated the ameliorative effects of acid hydrolyzed celery extract (HCE) and celery extract (CE) in an atopic dermatitis (AD) mice model. The results of the study showed that HCE, more than CE improved AD-like skin lesions caused by fluoro-2,4-dinitrobenzene and house dust mite antigen administration. Further analysis also showed the dominance of HCE than CE in preventing mast cell infiltration in the dermis; inhibiting the IL-31 expression in mice skin and reducing the immunoglobulin-E, IL-4, IL-5, TNF-α, IFN-γ, IL-31, and TSLP in serum of mice. Using in vitro studies in a murine macrophage cell line, we showed that apigetrin, luteolin, and apigenin present in both extracts could be accountable for the observed effects as these three compounds and not apiin prevented the nitric oxide production in the murine macrophage. Based on this study, we suggest that hydrolyzing celery extracts can improve the therapeutic efficacy of celery extracts for management of AD. PRACTICAL APPLICATIONS: Apigenin, apigetrin, and luteolin are known biologically active compounds present in celery. Acid hydrolysis could increase the biologically active compounds in natural products. The research investigated the effects of acid HCE in a mice model of atopic dermatitis. The data obtained from this study sheds light on the use of hydrolysis methods to improve the biological activities of plant extracts used in nutraceutical industries.

Neurodegenerative diseases are major threats to human health. Here, through fluorescence, colorimetric, immunoblotting, spectroscopy, and laser scanning confocal microscopic techniques, we investigated the neuroprotective properties of chlorogenic acid-rich Solanum melongena extracts (SM extract) in rotenone-induced PC-12 cell death. The results showed that rotenone caused apoptosis to PC-12 cells by elevating Bax/Bcl-2 ratio and increasing caspase-3 activity. Rotenone also increased ROS in cells while suppressing SOD and catalase activities. This resulted in the depletion of ATP in cells by blocking mitochondria complex I activity. Pretreatment of the cells with SM extract at concentrations of 100, 250, and 500 μg/ml before incubation for 24 hr with rotenone significantly prevented apoptosis, decreased ROS, and increased ATP production in the cells. SM extract upregulated SOD and catalase activities in the cells. These results unveil evidence that SM extract content neuroprotective properties that can be exploited to prevent and treat neurodegenerative diseases. PRACTICAL APPLICATIONS: Solanum melongena eggplant is a popular ingredient in many traditional recipes and is well known in Asia for its medicinal benefits. Despite numerous scientific reports of the potential health benefits of this plant, reports on its effects in neurodegenerative diseases is still lacking. This pilot study demonstrates that S. melongena eggplant can protect against neurotoxicity in neurodegenerative diseases. The results of this research serves as a base for further research on eggplant that will result in its usage on a larger scale as functional food materials.

The present study demonstrated the anti-obesity effects of enzyme-treated celery extract (ECE) in mice on high-fat diet (HFD). In vitro studies showed that ECE has anti-adipogenic properties by inhibiting lipid accumulations in adipose cells. In vivo studies indicated that the administration of ECE markedly prevented HFD-induced body weight gain, food efficiency ratio, and epididymal fat and liver weights. ECE reduced lipid parameters, cardiac risk factor, and atherogenic index in obese mice. ECE prevented a diabetes state by improving adipokines levels, reducing glucose levels, and preventing insulin resistance. Moreover, ECE prevented HFD-induced liver damage by preventing hepatic steatosis and upregulation of liver antioxidant enzymes. The mechanism of ECE was partially investigated to involve the activation of 5' adenosine monophosphate-activated protein kinase and hence the downregulation of CCAAT/enhancer binding protein α and peroxisome proliferator-activated receptor γ by ECE. Our results suggest that ECE could be used as functional food materials for the prevention of obesity. PRACTICAL APPLICATIONS: Apium graveolens is a popular plant with nutritive and medicinal benefits. It contains bioactive compounds such as apiin, apigenin, and luteolin. However, these compounds are rendered insoluble due to their interaction with polysaccharides in the cell wall thus making them less bioavailable. Hydrolyzing them could increase the yield of bioactive compounds in celery. This pilot study demonstrates that pectinase-treated celery extract has anti-obesity effects. The results of this research demonstrate the use of enzymes in improving the biological activities of plant extracts and suggest the use of enzyme-assisted extraction techniques in the industrial production of health functional food from celery.

IL-31 is a recently discovered cytokine that is produced not only in T-cells but also in mast cells. It is strongly implicated to play a key role in inflammatory diseases and in the pathogenesis of itch in atopic dermatitis. Apigenin, a flavonoid of plant origin has numerous biological applications. In this study, we showed that apigenin modulates IL-31 mRNA, protein expression, and release in stimulated human mast (HMC-1) by inhibiting the phosphorylation activation of MAPK and NF-&kappa, B. To determine whether apigenin has similar effects in vivo, using Compound 48/80, we developed an atopic dermatitis itch model in mice and found an increase in IL-31 expression in the skin. We also revealed that apigenin prevents the infiltration and degranulation of mast cells and suppressed mRNA and protein expression of IL-31 in the skin of mice. These results provide a new suggestion of the potential applicability of apigenin for treatment of various inflammatory diseases and itch mediated by IL-31.

Diospyros lotus is traditionally used for the treatment of diabetes, diarrhea, tumor, and hypertension. The purpose of this study was to investigate the anti-inflammatory effect and underlying molecular mechanisms of myricetin in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Myricetin dose-dependently suppressed the production of pro-inflammatory mediators (NO, iNOS, PGE2, and COX-2) in LPS-stimulated RAW264.7 macrophages. Myricetin administration decreased the production of NO, iNOS, TNF-α, IL-6, and IL-12 in mice. Myricetin decreased NF-κB activation by suppressing the degradation of IκBα, nuclear translocation of p65 subunit of NF-κB, and NF-κB DNA binding activity in LPS-stimulated RAW264.7 macrophages. Moreover, myricetin attenuated the phosphorylation of STAT1 and the production of IFN-β in LPS-stimulated RAW264.7 macrophages. Furthermore, myricetin induced the expression of HO-1 through Nrf2 translocation. In conclusion, these results suggest that myricetin inhibits the production of pro-inflammatory mediators through the suppression of NF-κB and STAT1 activation and induction of Nrf2-mediated HO-1 expression in LPS-stimulated RAW264.7 macrophages. This study has elucidated the anti-inflammatory effects of myricetin in in vitro and in vivo.

Muscat Bailey A grape stalk is an organic waste produced in marked amounts during the vinification of grapes. Previous studies have indicated that grape stalk is rich in bioactive phenolic compounds, and exhibits antioxidant and UV‑protective activities. However, its effects on obesity and obesity‑associated disorders have not yet been investigated. The effects of grape stalk extract on improving metabolic features were examined using a high‑fat diet (HFD)‑induced obesity mouse model. Oral administration of 200 mg/kg/day grape stalk extract over 16 weeks markedly prevented HFD‑induced obesity, hepatic steatosis, diabetic symptoms and the risk of developing cardiovascular disease. Furthermore, grape stalk extract prevented oxidative stress and inflammation caused by HFD in mice. The beneficial effect may be associated with CCAAT/enhancer‑binding protein α and peroxisome‑proliferator‑activated receptor γ down-regulation in liver tissue. Collectively, the results of the present study indicated that grape stalk extract may be a potent functional food ingredient for preventing obesity, hepatic steatosis and type 2 diabetes.

Diospyros (D.) lotus has been demonstrated to have antioxidant and anti‑inflammatory properties. The purpose of the present study was to evaluate the effect of D. lotus leaf water extract (DLE) on high‑fat diet (HFD)‑induced obesity in C57BL/6 mice. The present study first investigated the effect of DLE on the lipid accumulation and triglyceride (TG) contents in 3T3‑L1 cells, and the results revealed that treatment with DLE suppressed the lipid accumulation and TG level. Subsequently, the anti‑obesity effects of DLE were investigated in vivo. Oral administration of DLE reduced the body weight gain, food efficiency ratio, and liver and visceral fat weight in mice fed with a HFD. DLE administration in these mice also reduced TG, total cholesterol, low‑density lipoprotein cholesterol, glucose, insulin and leptin levels, as well as the atherogenic index. Furthermore, DLE administration decreased hepatic steatosis, as well as serum aspartate transaminase, alanine transaminase and alkaline phosphatase levels in mice fed with HFD. It was further observed that treatment of the HFD‑fed mice with DLE prevented lipid peroxidation, while it recovered glutathione depletion and the activities of superoxide dismutase, catalase and glutathione peroxidase. In conclusion, the current study suggests that the anti‑obesity effect of DLE may provide positive insights as a potential functional food ingredient for the prevention of obesity.

Ten compounds (1-10) isolated from the seeds of Cassia tora were evaluated for tyrosinase inhibition. Compounds 3, 4, and 7 inhibited tyrosinase enzymatic activity in a dose-dependent manner, with IC50 values of 3.0 ± 0.8, 7.0 ± 0.4, and 9.2 ± 3.4 μM, respectively. Kinetic analyses revealed a mechanism consistent with competitive inhibition. In silico molecular docking showed that compounds 3 and 4 docked in the active site of tyrosinase, whereas 7 interacted with Ala246 and Val248 at outside of the active site, and His244 and Glu256 at inside. Additionally, compounds 3, 4, and 7 suppressed melanogenesis in α-MSH-treated B16F10 melanoma cells at a concentration of 10 μM.

This study analyzed fruit stem extract (MGFE) from Muscat Bailey A grape (Vitis labrusca × Vitis vinifera) for their ameliorative effects on Ultraviolet B (UVB)-induced skin damage in Balb/c mice. Well established in vivo assays were used to determine the biological effects of MGFE upon UVB irradiation of BALB/c mice. The results showed that treatment with MGFE recovered glutathione depletion, prevented lipid peroxidation of tissues and decreased the expression of DNA repair enzyme oxo guanine glycosylase-1. MGFE recovered the skin conditions in UVB-irradiated Balb/c mice. Moreover, MGFE inhibited dermal infiltration of inflammatory cells and reduced serum tumor necrosis factor alpha and interleukin-6 levels. Finally, MGFE treatment inhibited UVB-induced melanin formation and collagen fiber destruction through the inhibition of matrix metalloproteinase-1 expression. Through high-performance liquid chromatography analysis, catechin, epicatechin, and trans-resveratrol were found to be among the main active compounds present in MGFE. Taken together, these results indicated that MGFE has potentials as topical therapeutic materials against skin damage by inhibiting oxidative stress and inflammatory.

Perilla (Perilla frutescens L.) leaves have shown therapeutic efficacy in the treatment of inflammatory disorders, allergies, bronchial asthma, and systemic damage due to free radicals. In the present study we analyzed the active constituents in perilla leaves using high-performance liquid chromatography (HPLC) and isolated luteolin, a polyphenolic flavonoid. We investigated the anti-inflammatory and antipruritic properties of luteolin. Luteolin inhibited the secretion of inflammatory cytokines such as interleukin-1β (IL-1 β) and tumor necrosis factor-α (TNF-α) from human mast cells (HMC-1) stimulated with phorbol myristate acetate plus calcium ionophore A23187 in a dose-dependent manner. Luteolin also significantly reduced the histamine release from rat peritoneal mast cells stimulated by compound 48/80, a potent histamine liberator. Furthermore, the administration of luteolin markedly inhibited the scratching behavior and vascular permeability induced by pruritogens, such as compound 48/80 or serotonin, in ICR mice. These results suggested that luteolin has potential as a therapeutic agent against inflammation and itch-related skin diseases.

Water-soluble polysaccharide (WSP) of Opuntia humifusa stems was extracted and its biological activities in mice fed with a high-fat diet (HFD) were investigated. The mice were treated with oral doses of WSP for 4 weeks. Body weight, fat mass, serum lipid, and hormone profiles, gastrointestinal tract changes were evaluated. WSP treatment resulted in a decrease in fat mass and improvement of lipid and hormone profiles associated with HFD consumption. In addition, WSP improved the gastrointestinal health of the mice by increasing ghrelin-releasing cells and serotonin-positive cells and boosted immune functions by increasing the expression of CD4+ cells and nitric oxide synthase. Also, WSP treatment reduced gastrointestinal transit time and increased fecal moisture content. These findings suggest that a sufficient intake of WSP from O. humifusa can be beneficial in preventing disorders that are associated with the consumption of HFD including the preservation of gastrointestinal health. PRACTICAL APPLICATIONS: Opuntia humifusa is a traditional edible plant widely eaten in Asia for its high concentrations of vitamin C, polyphenols, and flavonoids. The research investigated the biological activity of WSP extracted from O. humifusa stems. The data obtained from this study sheds light on the use of plant-based polysaccharides in nutraceutical industries as potential functional food materials for the prevention of HFD-related disorders and improvement of gastrointestinal health. The results of this research could serve as a base for further research on this polysaccharide as a source of functional polysaccharides and promotes its usage on a large scale in functional food materials.

s Ethnopharmacological relevance Panax ginseng (P. ginseng) is one of the most widely used medicinal plants due to its wide spectrum of medicinal effects. Among the currently available Panax ginseng products, Korea red ginseng (KRG) has been shown to exhibit a variety of antioxidative and hepatoprotective action. Aim of the study Our aim was to investigate the effects of KRG and its primary ginsenosides (Rg3 and Rh2) on EtOH-induced injury to mouse hepatocytes (TIB-73). Materials and methods We investigated the effects of KRG and its primary ginsenoside on EtOH-induced injury to TIB-73 cells and evaluated MAPKs signals as a possible mechanism of action. Hepatocytic injury was evaluated by biochemical assays as cell viability, lactate dehydrogenase (LDH), aspartate aminotransferase (AST), ROS and mitochondria membrane potential (MMP) level in TIB-73 cells. The levels of MAPK activation were analyzed by Western blots. Results The results showed that exposure of EtOH to TIB-73 cells led to cell death and membrane damage, accompanied by a decrease in cell viability, MMP, and Mg2+ concentrations, but an increase in LDH, AST, ROS and MAPK activation. KRG and its primary ginsenosides reduced EtOH-induced generation of ROS and the activation of ERK and JNK, and increased Mg2+ concentrations. Conclusion These results suggest that KRG and its primary ginsenosides inhibit EtOH-induced oxidative injury by suppression of the MAPK pathway in TIB-73 cells.

The aim of this study was to examine the proliferative ability of dibutyryl chitin (DBC) on scratch wounds in HaCaT keratinocytes and to evaluate the effect of nanoporous non-woven mat (DBCNFM) on skin wound healing in hairless mice using the advantages of DBCNFM, such as high porosity and high surface area to volume. The cell spreading activity of DBC was verified through a cell spreading assay in scratched human HaCaT keratinocytes. Scratch wound experiments showed that DBC notably accelerates the spreading rate of HaCaT keratinocytes in a dose dependent manner. The molecular aspects of the healing process were also investigated by hematoxylin & eosin staining of the healed skin, displaying the degrees of reepithelialization and immunostaining on extracellular matrix synthesis and remodeling of the skin. Topical application of DBCNFM significantly reduced skin wound rank scores and increased the skin remodeling of the wounded hairless mice in a dose dependent way. Furthermore, DBCNFM notably increased the expression of the type 1 collagen and filaggrin. These results demonstrate that DBC efficiently accelerates the proliferation of HaCaT keratinocytes and DBCNFM notably increases extracellular matrix synthesis on remodeling of the skin, and these materials are a good candidate for further evaluation as an effective wound healing agent.

The aim of the study was to investigate the ameliorative effects and the mechanism of action of L-2-oxothiazolidine-4-carboxylate (OTC) on acetaminophen (APAP)-induced hepatotoxicity in mice. Mice were randomly divided into six groups: normal control group, APAP only treated group, APAP + 25 mg/kg OTC, APAP + 50 mg/kg OTC, APAP + 100 mg/kg OTC, and APAP + 100 mg/kg N-acetylcysteine (NAC) as a reference control group. OTC treatment significantly reduced serum alanine aminotransferase and aspartate aminotransferase levels in a dose dependent manner. OTC treatment was markedly increased glutathione (GSH) production and glutathione peroxidase (GSH-px) activity in a dose dependent manner. The contents of malondialdehyde and 4-hydroxynonenal in liver tissues were significantly decreased by administration of OTC and the inhibitory effect of OTC was similar to that of NAC. Moreover, OTC treatment on APAP-induced hepatotoxicity significantly reduced the formation of nitrotyrosin and terminal deoxynucleotidyl transferase dUTP nick end labeling positive areas of liver tissues in a dose dependent manner. Furthermore, the activity of caspase-3 in liver tissues was reduced by administration of OTC in a dose dependent manner. The ameliorative effects of OTC on APAP-induced liver damage in mice was similar to that of NAC. These results suggest that OTC has ameliorative effects on APAP-induced hepatotoxicity in mice through anti-oxidative stress and anti-apoptotic processes.

Inflammation is a highly complex process that protects against foreign challenge or tissue injury. The ester derivative dibutyryl chitin (DBC) reportedly accelerates wound healing and exerts an anti-inflammatory effect. However, little is known regarding the inhibitory effect of DBC in anti-inflammation. In this study, we investigated the effect of DBC on the inducible nitric oxide synthetase (iNOS) and cyclooxygenage-2 (COX-2) pathways and pro-inflammatory cytokine production in lipopolysaccharide (LPS)-treated RAW 264.7 macrophages. Our results demonstrate that DBC (MW 3,772) significantly inhibits overproduction of NO and PGE(2) as well as pro-inflammatory cytokines, such as tumor necrosis factor-α and interleukin-1β, in LPS-stimulated RAW 264.7 macrophages. Inhibition of NO and PGE(2) overproduction in LPSstimulated RAW 264.7 macrophages by DBC was mediated through the down-regulation of iNOS and COX-2 expression. These results demonstrate that DBC efficiently inhibits inflammation and has potential as an effective anti-inflammatory and wound healing agent.

Mite antigen, extract from Dermatophagoides farinae in house dust, is a well-known causative agent of atopy or allergic diseases, which involves many inflammatory cytokines/chemokines expression. Heme oxygenase 1 (HO1) has recently emerged as an important cytoprotective enzyme against oxidative stress and inflammatory responses in many cell types.The aim of this study was to investigate the possible mechanism by which wogonin, a natural product isolated from Scutellaria baicalensis, inhibited the mite antigen-induced chemokine expression in human keratinocytes, HaCaT cells.The level of chemokine expression was measured by reverse transcription-polymerase chain reaction (RT-PCR) and signaling study was performed by Western blot analysis.The mite antigen-induced thymus- and activation-regulated chemokine (TARC/CCL17) expression in a dose-dependent manner via extracellular signal-regulated kinase (ERK) activation. However, it did not affect the expression of other chemokines including macrophage-derived chemokine (MDC/CCL22), RANTES, and IL-8. Interestingly, wogonin significantly suppressed the mite antigen-induced TARC expression via the induction of HO1. This suppression was completely restored by HO1 siRNA, suggesting a direct role of HO1 for the suppressive effect. Furthermore, exogenous CO, but not other end products of HO1 activity, also suppressed the mite antigen-induced TARC expression.Wogonin induces HO1 expression, which in turn HO1 and/or CO suppresses TARC expression induced by mite antigen in human HaCaT cells.

Nitric oxide (NO), synthesized from L-arginine by NO synthases, is a small, lipophilic, diffusible, highly reactive molecule with dichotomous regulatory roles in many biological events under physiological and pathological conditions. NO can promote apoptosis (pro-apoptosis) in some cells, whereas it inhibits apoptosis (anti-apoptosis) in other cells. This complexity is a consequence of the rate of NO production and the interaction with biological molecules such as metal ion, thiol, protein tyrosine, and reactive oxygen species. Long-lasting overproduction of NO acts as a pro-apoptotic modulator, activating caspase family proteases through the release of mitochondrial cytochrome c into cytosol, up-regulation of the p53 expression, and alterations in the expression of apoptosis-associated proteins, including the Bcl-2 family. However, low or physiological concentrations of NO prevent cells from apoptosis that is induced by the trophic factor withdrawal, Fas, TNFalpha/ActD, and LPS. The anti-apoptotic mechanism is understood on the basis of gene transcription of protective proteins. These include: heat shock protein, hemeoxygenase, or cyclooxygenase-2 and direct inhibition of the apoptotic executive effectors caspase family protease by S-nitrosylation of the cysteine thiol group in their catalytic site in a cell specific way. Our current understanding of the mechanisms by which NO exerts both pro- and anti-apototic action is discussed in this review article.

Stylopine is a major component of the leaf of Chelidonium majus L. (Papaveraceae), which has been used for the removal of warts, papillomas and condylomas, as well as the treatment of liver disease, in oriental countries. Stylopine per se had no cytotoxic effect in unstimulated RAW 264.7 cells, but concentration-dependently reduced nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta), and the IL-6 production and cyclooxygenase-2 (COX-2) activity caused by the LPS stimulation. The levels of inducible nitric oxide synthase (iNOS) and COX-2 protein expressions were markedly suppressed by stylopine in a concentration dependent manner. These results suggest that stylopine suppress the NO and PGE2 production in macrophages by inhibiting the iNOS and COX-2 expressions. These biological activities of stylopine may contribute to the anti-inflammatory activity of Chelidonium majus.

The inhibitory effects of tanshinone IIA, a diterpene isolated from Salvia miltiorrhiza root, on the production of nitric oxide (NO), interleukin-1beta (IL-1beta), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), and the expression of inducible nitric oxide synthase (iNOS) were investigated in activated RAW 264.7 cells. This compound markedly inhibited the production of NO, IL-1beta and TNF-alpha, and suppressed the expression of iNOS in a dose-dependent manner. These results suggest that the traditional use of S. miltiorrhiza as an anti-inflammatory herbal medicine may be explained, in part, by the inhibition of NO, IL-1beta, IL-6 and TNF-alpha production, and expression of iNOS.

CD38 is a bifunctional enzyme synthesizing (ADP-ribosyl cyclase) and degrading (cyclic ADP-ribose (cADPR) hydrolase) cADPR, a potent Ca(2+) mobilizer from intracellular pools. CD38 internalization has been proposed as a mechanism by which the ectoenzyme produced intracellular cADPR, and thiol compounds have been shown to induce the internalization of CD38. Here, we show that the disulfide bond between Cys-119 and Cys-201 in CD38 may be involved in CD38 dimerization and internalization. We tested the effect of a reducing agent, l-2-oxothiazolidine-4-carboxylic acid (OTC), a prodrug of cysteine, on CD38 internalization in pancreatic islets. OTC enhanced insulin release from isolated islets as well as CD38 internalization and cytoplasmic Ca(2+) level. Furthermore, islet cells treated with antisense CD38 oligonucleotide showed inhibition of OTC-induced insulin secretion. Intake of OTC in db/db mice ameliorated glucose tolerance, insulin secretion, and morphology of islets when compared with control mice. These data indicate that OTC improves glucose tolerance by enhancing insulin secretion via CD38/cADPR/Ca(2+) signaling machinery. Thus, OTC may represent a novel class of antidiabetic drug.