Unsaturated Fatty Acids Complex Regulates Inflammatory Cytokine Production through the Hyaluronic Acid Pathway.

In this study, we aimed to develop natural and/or functional materials with antioxidant and anti-inflammatory effects. We obtained extracts from natural plants through an oil and hot-water extraction process and prepared an extract composite of an effective unsaturated fatty acid complex (EUFOC). Furthermore, the antioxidant effect of the extract complex was evaluated, and the anti-inflammatory effect was explored by assessing its inhibitory effect on nitric oxide production through its HA-promoting effect. We conducted a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assay to evaluate the cell viability of the EUFOC, and the results showed that EUFOC was not cytotoxic at the test concentrations. In addition, it showed no endogenous cytotoxicity in HaCaT (human keratinocyte) cells. The EUFOC showed excellent 1,1-diphenyl-2-picrylhydrazyl- and superoxide-scavenging abilities. Moreover, it exerted an inhibitory effect on NO production at concentrations that did not inhibit cell viability. The secretion of all the cytokines was increased by lipopolysaccharide (LPS) treatment; however, this was inhibited by the EUFOC in a concentration-dependent manner. In addition, hyaluronic acid content was markedly increased by the EUFOC in a dose-dependent manner. These results suggest that the EUFOC has excellent anti-inflammatory and antioxidant properties, and hence, it can be used as a functional material in various fields.

Oral administration of Ulmus davidiana extract suppresses interleukin-1ß expression in LPS-induced immune responses and lung injury.

BACKGROUND: Ulmus davidiana (UD) is a traditional Korean herb medicine that is used to treat inflammatory disorders. UD has been shown to modulate a number of inflammatory processes in vitro or in vivo studies. However, the molecular mechanisms of UD on lipopolysaccharide (LPS)-induced acute lung injury remain to be understood. OBJECTIVE: The primary objective of this study is to determine the effect of UD bark water extract on LPS-induced immune responses and lung injury using both in vitro and in vivo models. METHODS: RAW 264.7 cells and a rat model of acute lung injury (ALI) were used to study the effects of UD on several parameters. Nitrite level, lactate dehydrogenase (LDH) level, and superoxide dismutase (SOD) activities were measured. Tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and plasma transaminase activities in blood were also determined. Pathological investigations were also performed. RESULTS: LPS infusion resulted in elevated IL-1ß mRNA expression, nitrite levels, TNF-α expression, and IL-1ß expression in RAW 264.7 cells. LPS infusion also increased levels of nitrite/nitrate, total protein, LDH, and TNF-α in bronchoalveolar lavage fluid, but reduced SOD levels in ex vivo and in vivo models. UD administration ameliorated all these inflammatory markers. In particular, treatment with UD reduced LPS-induced nitrite production in RAW 264.7 cells in a dose-dependent manner. UD treatment also counteracted the LPS-induced increase in alanine aminotransferase (ALT) and aspartate transaminase (AST) activity in rat plasma, leading to a significant reduction in ALT and AST activity. CONCLUSIONS: The results revealed that UD treatment reduces LPS-induced nitrite production, IL-1ß mRNA expression, and TNF-α expression. In addition, LPS-induced decrease in SOD level is significantly elevated by UD administration. These results indicate that UD extract merits consideration as a potential drug for treating and/or preventing ALI.

Red Ginseng Reduces Inflammatory Response via Suppression MAPK/P38 Signaling and p65 Nuclear Proteins Translocation in Rats and Raw 264.7 Macrophage.

Lipopolysaccharides (LPS) cause systemic inflammatory responses, which are characterized by high mortality and multiple signs, including metabolic disturbances, respiratory acidosis, hypotension, and vital organs disorder. Cytokines secretion and oxidative stress are the main features of the disease. Diagnosis and treatment of systemic inflammation (SI) remain a challenge. Korean Red Ginseng (RG) is one of medicinal herbs that showed a potent anti-oxidant effect. We aimed to study the protective effects of RG on systemic inflammatory response in rats and RAW 264.7 macrophage cells induced by LPS. The rats were treated with water and alcohol extracts of RG for four weeks to prevent the inflammatory response. The result showed that LPS toxin increased morbidity and mortality, and induced liver, kidney, and lung injuries manifested by deteriorated biomarkers. Hypotension, hypomagnesemia, acidosis, and oxidative stress were observed in septic rats. However, RG extracts attenuated liver, kidney, and lung enzymes and metabolites in treated groups via its anti-inflammatory and anti-oxidant properties. Furthermore, RG improved magnesium and blood pressure in the treated groups. RAW 264.7 macrophage cells exposed to LPS disturbance in translocation of p65 and MAPK/p38. Nevertheless, RG-pretreated cells did not significantly alter. In conclusion, RG reduced the rates of mortality and morbidity of treated rats - liver, kidney, and lung injuries were protected in the treated groups through the potentiation of anti-oxidant defense. RG was able to conserve mitochondrial function, inhibiting the activation of MAPK/p38 signaling and suppressing NF-κB p65 cytoplasm-nucleus transport. Further studies are needed to examine the effects on chronic conditions in animal models and human.

Distribution, accumulation, and potential risk of polybrominated diphenyl ethers in the marine environment receiving effluents from a sewage treatment plant.

We investigated the effect of sewage treatment plant effluent on the distribution and accumulation of polybrominated diphenyl ethers (PBDEs) in the marine environment. PBDEs concentrations in seawater and surface sediments were within the ranges 1.58-6.94 ng/L and 2.18-307 ng/g dw, respectively. PBDE concentrations in sediments gradually decreased with increasing distance from inner bay including the sewage outfall. The contribution of effluent to PBDE distributions was very limited. The concentrations of PBDEs in sediment core decreased exponentially with increasing depth. PBDE concentrations in oysters were 4.7-37 ng/g lw. BDE-209 was the dominant congener in marine environmental samples receiving effluent. Estimated dietary exposures of PBDEs by seafood were 0.01-0.08 ng/kg body weight/day, which were more than six orders of magnitude lower than the reported levels of PBDEs with the no observable adverse effects. Hazard quotients demonstrated that, at present, PBDEs posed no potential risk to benthic organisms in the study area.

Identification of genotoxic compounds in crude oil using fractionation according to distillation, polarity and Kow.

We examined the degree of DNA damage caused by fractions of crude oil in accordance with the boiling points, polarity and log Kow. Relatively high DNA damage was observed in the aromatic fraction (290-330°C) and resin and polar fraction (350-400°C). The resin and polar fraction showed relatively high genotoxicity compared with the aliphatic and aromatic fraction at the 1-4 log Kow range. At the 6-7 log Kow range, the aromatic fraction showed relatively high DNA damage compared with the aliphatic and resin and polar fraction. In particular, every detailed fraction in accordance with the log Kow values (aliphatic and aromatic (310-320°C) and resins and polar fractions (370-380°C)) showed one or less than one DNA damage. However, the fractions before separation in accordance with log Kow values (aliphatic and aromatic (310-320°C) and resin and polar (370-380°C) fractions) showed high DNA damage. Thus, we confirm the synergistic action between the detailed compounds.

Antidiabetic Effects of Yam (Dioscorea batatas) and Its Active Constituent, Allantoin, in a Rat Model of Streptozotocin-Induced Diabetes.

The objective of this study was to investigate the therapeutic efficacies of crude yam (Dioscorea batatas) powder (PY), water extract of yam (EY), and allantoin (the active constituent of yam) in streptozotocin (STZ)-induced diabetic rats with respect to glucose, insulin, glucagon-like peptide-1 (GLP-1), C-peptide, glycated hemoglobin (HbAlc), lipid metabolism, and oxidative stress. For this purpose, 50 rats were divided into five groups: normal control (NC), diabetic control (STZ), and STZ plus treatment groups (STZ + PY, STZ + EY, and STZ + allantoin). After treatment for one-month, there was a decrease in blood glucose: 385 ± 7 in STZ, 231 ± 3 in STZ + PY, 214 ± 11 in STZ + EY, and 243 ± 6 mg/dL in STZ + allantoin, respectively. There were significant statistical differences (p < 0.001) compared to STZ (100%): 60% in STZ + PY, 55% in STZ + EY, and 63% in STZ + allantoin. With groups in the same order, there were significant decreases (p < 0.001) in HbAlc (100% as 24.4 ± 0.6 ng/mL, 78%, 75%, and 77%), total cholesterol (100% as 122 ± 3 mg/dL, 70%, 67%, and 69%), and low-density lipoprotein (100% as 29 ± 1 mg/dL, 45%, 48%, and 38%). There were also significant increases (p < 0.001) in insulin (100% as 0.22 ± 0.00 ng/mL, 173%, 209%, and 177%), GLP-1 (100% as 18.4 ± 0.7 pmol/mL, 160%, 166%, and 162%), and C-peptide (100% as 2.56 ± 0.10 ng/mL, 129%, 132%, and 130%). The treatment effectively ameliorated antioxidant stress as shown by a significant decrease (p < 0.001) in malondialdehyde (100% as 7.25 ± 0.11 nmol/mL, 87%, 86%, and 85%) together with increases (p < 0.01) in superoxide dismutase (100% as 167 ± 6 IU/mL, 147%, 159%, and 145%) and reduced glutathione (100% as 167 ± 6 nmol/mL, 123%, 141%, and 140%). The results indicate that yam and allantoin have antidiabetic effects by modulating antioxidant activities, lipid profiles and by promoting the release of GLP-1, thereby improving the function of ß-cells maintaining normal insulin and glucose levels.

DNA damage caused by organic extracts of contaminated sediment, crude, and weathered oil and their fractions recovered up to 5 years after the 2007 Hebei Spirit oil spill off Korea.

We examined the degree of DNA damage caused by three fractions (F1, aliphatic hydrocarbons; F2, aromatic hydrocarbons; and F3, polar compounds) of the organic extract of sediments taken from Taean, Korea, following the Hebei Spirit oil spill. DNA damage was measured using the comet assay with blood cells of the striped beakfish (Oplegnathus fasciatus). DNA damage was also examined for fractions of crude oil (Iranian Heavy Crude Oil, IHC), weathered oil and six subfractions (F2.1-F2.6). The greatest DNA damage was found from the Sinduri dune region and DNA damage decreased to 40% weathered oil in F2 fraction compared with crude oil. The DNA damage of the sum of fractions was found higher than the organic extracts of sediments, suggesting antagonistic interactions between the genotoxic compounds. This study confirmed the persistence of potential genotoxicity in sediments of the severely affected regions as long as 5 years after the oil spill.

Effect-directed analysis and mixture effects of AhR-active PAHs in crude oil and coastal sediments contaminated by the Hebei Spirit oil spill.

The major AhR-active PAHs were identified in crude oil and oil-contaminated sediments by use of effect-directed analysis. As part of the study, an enhanced potency balance analysis was conducted by establishing the novel relative potency values of (alkyl)-PAHs from the H4IIE-luc bioassay. Silica gel column fractionation of crude oil resulted in greater AhR-mediated potencies in fractions of aromatics (F2) and resins (F3), and such trend was also observed for field collected sediment samples. AhR-mediated potencies of six F2 sub-fractions from HPLC indicated that the majority of F2 responses were attributable to 3-4 ring aromatics. Target PAHs including C4-phenanthrene, C1-chrysene, and C3-chrysene in sediments explained ∼ 18% of the bioassay-derived TCDD-EQs, however, the unknown AhR agonists and potential mixture effects remain in question. Overall, the AhR-potency and antagonistic potential of residual oil in sediment tended to decrease over time, thus monitoring of weathering process would be key for the post management of oil-contaminated sites.

Mesocosm study on weathering characteristics of Iranian Heavy crude oil with and without dispersants.

The environmental fate of Iranian Heavy crude oil (IHC) with and without an added oil spill dispersant (OSD) has been studied using a 1000 kL capacity in situ mesocosm. Physical weathering and chemical composition changes of the oil were monitored for 77 days. Compound-specific effects of the OSD could be observed as changes over time in the content of the total petroleum hydrocarbon (TPH), unresolved complex mixture (UCM), alkanes, polycyclic aromatic hydrocarbons (PAHs), hopanes and steranes in the oil. As oil weathers, most hydrocarbons showed a rapid decreasing phase followed by a slowdown and stabilization. Recalcitrant biomarkers, however, showed a different trend. An increase in hydrocarbon contents in the form of UCM occurred after OSD treatment. The enhanced solubility of the low molecular weight PAHs by the OSD decreased the half-life of the alkylated PAHs in the OD. After 77 days of exposure at the sea surface, both the oils with and without the OSD exhibited moderate weathering. Most of the source diagnostic indices maintained their source information, and the weathering indices indicated that evaporation, dissolution, and dispersion were the major weathering processes. The mass balance of the weathered oil was calculated using laboratory and mesocosm data and the results demonstrate the importance of using a mesocosm for the production of environmentally realistic data.

Korean red ginseng and its primary ginsenosides inhibit ethanol-induced oxidative injury by suppression of the MAPK pathway in TIB-73 cells.

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 Mg(2+) 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 Mg(2+) 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.

Temporal and geographical trends in the genotoxic effects of marine sediments after accidental oil spill on the blood cells of striped beakperch (Oplegnathus fasciatus).

To determine the impact of genetic toxicity caused by the Hebei Spirit oil spill on December 7, 2007, we measured DNA damage in the blood cells of striped beakperch in vitro after exposure to extracts from sediments in the Taean area. The objective of this study was to investigate temporal changes of toxic effects caused by residual PAHs in the sediments up to 18 months after an oil spill. In conclusion, DNA damage had reduced over this 18-month period; that is, the sediments recovered quickly from the oil pollution. In addition, statistically significant correlations between PAHs and DNA damage were observed. Because the comet assay is sensitive to DNA damage induced by genotoxic substances from the polluted sediments, the comet assay can be considered a useful tool as a biomarker in investigating genetic toxicity in environmental monitoring and elucidating the recovery of oil pollution after oil spill as well.

Taurine prevents hypertension and increases exercise capacity in rats with fructose-induced hypertension.

BACKGROUND: Fructose-induced hypertension was used to test the hypothesis that taurine supplementation and/or exercise can prevent hypertension and increase exercise capacity. METHODS: Five groups of 15 Sprague-Dawley rats were allocated and designated as control, high fructose-fed (fructose), high fructose-fed plus exercise (FE), high fructose-fed plus 2% taurine supplement (FT) and high fructose-fed plus 2% taurine supplement and exercise (FET) groups. Noninvasive systolic blood pressure (SBP) was recorded weekly and invasive arterial blood pressure (ABP) was recorded at the end of the 4-week trial. Three consecutive swimming tests were performed in the selected rats from each group and the plasma biomarkers were measured in the remaining rats. RESULTS: Noninvasive SBP differed significantly (P < 0.001) from week 3, both noninvasive and invasive ABP increased significantly (P < 0.001), and exercise capacity significantly decreased (P < 0.001) in the fructose group compared with the control group. The individual effects of swimming and taurine supplementation were incapable of preventing the development of hypertension and SBP significantly (P < 0.001) increased in the FE and FT groups; exercise capacity in those groups remained similar to control. The combined effects of exercise and taurine alleviated hypertension and significantly increased exercise capacity in the FET group. Insulin resistance increased significantly and plasma nitric oxide (NO) decreased significantly in the F, FE, and FT groups. Both parameters remained similar to control values in the FET group with an increasing antioxidant activity. CONCLUSION: Taurine supplementation in combination with exercise prevents hypertension and increases exercise capacity by possibly antioxidation and maintaining NO concentrations.