Kushenol C from Sophora flavescens protects against UVB-induced skin damage in mice through suppression of inflammation and oxidative stress.

Sophora flavescens has been used in traditional medicine for the treatment of various diseases such as viral hepatitis, fever, cancer, and pain. It is known to contain many bioactive compounds including prenylated flavonoids such as kurarinone, sophoraflavanone G, kuraridine and isoxanthohumol. These flavonoids have been confirmed to have anti-inflammatory, α-glucosidase inhibitory and antioxidant performances. However, the protective activities against UV-induced skin damage of kushenol C from S. flavescens have not yet been elucidated. In this study, we explored the protective effect of kushenol C against the skin damage induced by UVB in mice. Our results showed that kushenol C treatment significantly recovered UVB-induced skin damage, the degradation of collagen, mast cell infiltration, together with epidermal hyperplasia in mice. Furthermore, the treatment of kushenol C remarkably suppressed the generation of pro-inflammatory mediators in the mice irradiated by UVB. More so, treatment with kushenol C suppressed the oxidative stress in mice irradiated by UVB. In conclusion, these results showed that kushenol C from S. flavescens has potentialities to treat skin injury via suppressing skin damage induced by UVB and oxidative stress.

Anti-inflammatory of disenecionyl cis-khellactone in LPS-stimulated RAW264.7 cells and the its inhibitory activity on soluble epoxide hydrolase.

The objective of the present study was to investigate anti-inflammatory effects of disenecionyl cis-khellactone (DK) isolated from Peucedanum japonicum Thunberg, a traditional edible plant, in RAW264.7 cells stimulated with lipopolysaccharide (LPS). Anti-inflammatory effects of DK were analyzed using various techniques, including NO assay, Western blot analysis, enzyme-linked immunosorbent assay (ELISA), real-time PCR, and immunofluorescence staining. It was revealed that DK reduced the production of pro-inflammatory cytokines including Monocyte chemoattractant protein-1 (MCP-1), Tumor necrosis factor-α (TNF-α), Interleukin 1ß (IL-1ß), and Interleukin 6 (IL-6) in RAW264.7 cells stimulated with LPS. It was revealed that DK effectively downregulated expression levels of iNOS and COX-2 due to inhibition of NF-κB activation and suppressing the phosphorylation of p38 and jun N-terminal kinase (JNK) mitogen-activated protein kinase (MAPK) phosphorylation. Also, soluble epoxide hydrolase activity and expression were decreased by the proinflammatory inhibitor, DK. Finally, findings of this study suggest that DK isolated from P. japonicum might have potential as a therapeutic candidate for inflammatory diseases.

Diospyros lotus leaf extract and its main component myricitrin regulate pruritus through the inhibition of astrocyte activation.

Diospyros lotus is a deciduous plant native to Asian countries, including Korea, Japan and China, and southeast Europe. In traditional medicine, Diospyros lotus is used as an anticancer, antidiabetic and antipyretic agent. The present study aimed to evaluate the effect of Diospyros lotus leaf extract (DLE) in ameliorating histamine-independent pruritus. Activation of signal transducer and activator of transcription 3 (STAT3) in astrocytes contributes to pruritus. In this study, the effects of DLE and its main component, myricetin (MC), on the activation of STAT3, expression of glial fibrillary acidic protein (GFAP), and production of lipocalin-2 (LCN2) in IL-6-treated astrocytes and chloroquine-injected mice were investigated through western blot, reverse transcription-quantitative PCR, and immunofluorescence staining. DLE and MC inhibited STAT3 activation, GFAP expression and LCN2 release via inositol 1,4,5-trisphosphate receptor type 1 blockade in astrocytes. DLE and MC ameliorated scratching behavior, expression of GFAP, mast cell infiltration and serum IL-6 levels in chloroquine-injected mice. These results suggested that DLE and MC can be used as oral therapeutic agents for the treatment and management of pruritus.

Anti-inflammatory effect of red ginseng marc, Artemisia scoparia, Paeonia japonica and Angelica gigas extract mixture in LPS-stimulated RAW 264.7 cells.

A normal inflammatory response is essential in protecting the body from foreign substances. However, excessive inflammation contributes to diseases such as oxidative stress, heart disease, and cancer. In this study, we evaluated the anti-inflammatory effects of RAPA (red ginseng marc, Artemisia scoparia Waldst.et Kit, Paeonia japonica Miyabe & Takeda, and Angelica gigas Nakai extract mixture) in LPS-stimulated RAW 264.7 cells (macrophages). RAPA suppressed the expression of inflammatory factors such as iNOS and COX-2 and decreased the production of nitric oxide. In addition, RAPA decreased the expression of the inflammatory cytokines TNF-α and IL-6. Furthermore, RAPA inhibited the phosphorylation of MAPKs such as JNK and ERK as well as IκB and NF-κB. In conclusion, RAPA inhibited production of inflammatory mediators via downregulation of the MAPK and NF-κB signaling pathways in LPS-stimulated RAW 264.7 cells. The results of this study demonstrated that RAPA regulates excessive inflammatory responses at the cellular level. Therefore, it is necessary to investigate whether the same effect is observed in vivo through further research.

Anti­inflammatory effect of Chrysanthemum zawadskii, peppermint, Glycyrrhiza glabra herbal mixture in lipopolysaccharide­stimulated RAW264.7 macrophages.

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 anti­inflammatory 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 anti­inflammatory activity of the CPG mixture. Pretreatment of Raw264.7 cells with CPG inhibited the increase of inflammatory mediators (inducible nitric oxide synthase, cyclooxygenase­2 and IFN­ß) induced by LPS. Additionally, it inhibited the production of pro­inflammatory cytokines (TNF­α, IL­6 and IL­1ß). CPG suppressed LPS­induced phosphorylation of STAT1, AKT, Iκb and NF­κB. Furthermore, CPG inhibited the translocation of NF­κB into the nucleus. In summary, CPG could inhibit LPS­induced inflammation, which occurs primarily through the AKT/Iκb/NF­κB signaling pathway in RAW264.7 cells.

Kushenol C Prevents Tert-Butyl Hydroperoxide and Acetaminophen-Induced Liver Injury.

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.

In vitro Anti-Inflammatory and Anti-Oxidative Stress Activities of Kushenol C Isolated from the Roots of Sophora flavescens.

Kushenol C (KC) is a prenylated flavonoid isolated from the roots of Sophora flavescens aiton. Little is known about its anti-inflammatory and anti-oxidative stress activities. Here, we investigated the anti-inflammatory and anti-oxidative stress effects of KC in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages, and tert-butyl hydroperoxide (tBHP)-induced oxidative stress in HaCaT cells. The results demonstrated that KC dose-dependently suppressed the production of inflammatory mediators, including NO, PGE2, IL-6, IL1ß, MCP-1, and IFN-ß in LPS-stimulated RAW264.7 macrophages. The study demonstrated that the inhibition of STAT1, STAT6, and NF-κB activations by KC might have been responsible for the inhibition of NO, PGE2, IL-6, IL1ß, MCP-1, and IFN-ß in the LPS-stimulated RAW264.7 macrophages. KC also upregulated the expression of HO-1 and its activities in the LPS-stimulated RAW264.7 macrophages. The upregulation of Nrf2 transcription activities by KC in the LPS-stimulated RAW264.7 macrophages was demonstrated to be responsible for the upregulation of HO-1 expression and its activity in LPS-stimulated RAW264.7 macrophages. In HaCaT cells, KC prevented DNA damage and cell death by upregulating the endogenous antioxidant defense system involving glutathione, superoxide dismutase, and catalase, which prevented reactive oxygen species production from tert-butyl hydroperoxide (tBHP)-induced oxidative stress in HaCaT cells. The upregulated activation of Nrf2 and Akt in the PI3K-Akt signaling pathway by KC was demonstrated to be responsible for the anti-oxidative stress activity of KC in HaCaT cells. Collectively, the study suggests that KC can be further investigated as a potential anti-inflammatory candidate for the treatment of inflammatory diseases.

Anti-obesity effects of enzyme-treated celery extract in mice fed with high-fat diet.

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.

Chlorogenic acid-rich Solanum melongena extract has protective potential against rotenone-induced neurotoxicity in PC-12 cells.

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.

Biological activities of water-soluble polysaccharides from Opuntia humifusa stem in high-fat-diet-fed mice.

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.

Muscat Bailey A grape stalk extract ameliorates high-fat diet­induced obesity by downregulating PPARγ and C/EPBα in mice.

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 UV­protective activities. However, its effects on obesity and obesity­associated disorders have not yet been investigated. The effects of grape stalk extract on improving metabolic features were examined using a high­fat diet (HFD)­induced obesity mouse model. Oral administration of 200 mg/kg/day grape stalk extract over 16 weeks markedly prevented HFD­induced 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/enhancer­binding protein α and peroxisome­proliferator­activated receptor Î³ 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.

Ameliorative effects of fruit stem extract from Muscat Bailey A against chronic UV-induced skin damage in BALB/c mice.

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.

Tyrosinase inhibitory components from the seeds of Cassia tora.

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.

Protective effects of grape stem extract against UVB-induced damage in C57BL mice skin.

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.

Enhanced biological activities of gamma-irradiated persimmon leaf extract.

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.

Anti-inflammatory activity of myricetin from Diospyros lotus through suppression of NF-κB and STAT1 activation and Nrf2-mediated HO-1 induction in lipopolysaccharide-stimulated RAW264.7 macrophages.

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-ß 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.

Anti-inflammatory and antipruritic effects of luteolin from Perilla (P. frutescens L.) leaves.

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-1ß (IL-1 ß) 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.

Antioxidant effect of astragalin isolated from the leaves of Morus alba L. against free radical-induced oxidative hemolysis of human red blood cells.

We evaluated the antioxidant properties of mulberry leaves extract (MLE) and flavonoids isolated from MLE. MLE was prepared by extraction with methanol. Flavonoids were analyzed by high-performance liquid chromatography. Oxidative hemolysis of normal human red blood cells (RBCs) was induced by the aqueous peroxyl radical [2,2'-Azobis (2-amidinopropane) dihydrochloride, AAPH]. MLE contained three flavonoids in the order quercetin (QC) > kaempferol (KF) > astragalin (AG). Oxidative hemolysis of RBCs induced by AAPH was suppressed by MLE, AG, KF, and QC in a time- and dose-dependent manner. MLE and these three flavonoids prevented the depletion of cystosolic antioxidant glutathione (GSH) in RBCs. AG had the greatest protective effect against AAPH-induced oxidative hemolysis and GSH depletion in RBCs.

The ameliorative effects of L-2-oxothiazolidine-4-carboxylate on acetaminophen-induced hepatotoxicity in mice.

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.

Inhibitory effect of dibutyryl chitin ester on nitric oxide and prostaglandin E2 production in LPS-stimulated RAW 264.7 cells.

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-1ß, 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.