Luteolin supplementation during porcine oocyte maturation improves the developmental competence of parthenogenetic activation and cloned embryos.

Luteolin (Lut), a polyphenolic compound that belongs to the flavone subclass of flavonoids, possesses anti-inflammatory, cytoprotective, and antioxidant activities. However, little is known regarding its role in mammalian oocyte maturation. This study examined the effect of Lut supplementation during in vitro maturation (IVM) on oocyte maturation and subsequent developmental competence after somatic cell nuclear transfer (SCNT) in pigs. Lut supplementation significantly increased the proportions of complete cumulus cell expansion and metaphase II (MII) oocytes, compared with control oocytes. After parthenogenetic activation or SCNT, the developmental competence of Lut-supplemented MII oocytes was significantly enhanced, as indicated by higher rates of cleavage, blastocyst formation, expanded or hatching blastocysts, and cell survival, as well as increased cell numbers. Lut-supplemented MII oocytes exhibited significantly lower levels of reactive oxygen species and higher levels of glutathione than control MII oocytes. Lut supplementation also activated lipid metabolism, assessed according to the levels of lipid droplets, fatty acids, and ATP. The active mitochondria content and mitochondrial membrane potential were significantly increased, whereas cytochrome c and cleaved caspase-3 levels were significantly decreased, by Lut supplementation. These results suggest that Lut supplementation during IVM improves porcine oocyte maturation through the reduction of oxidative stress and mitochondria-mediated apoptosis.

Photoprotective Effect of Fermented and Aged Mountain-Cultivated Ginseng Sprout (Panax ginseng) on Ultraviolet Radiation-Induced Skin Aging in a Hairless Mouse Model.

Interest in foods that promote inner beauty increases with increases in exposure to ultraviolet (UV) rays and with improvements in quality of life. This study was performed to evaluate the efficacy of fermented and aged mountain-cultivated ginseng sprouts (FAMCGSs), which have higher anti-inflammatory and antioxidant effects compared to mountain-cultivated ginseng sprouts (MCGSs), as an inner beauty enhancing food. The effect of orally administered FAMCGSs on UV type B (UVB) radiation-induced skin aging was investigated in a hairless mouse model through analyzing skin parameters including epidermal thickness, transepidermal water loss (TEWL), roughness, moisture, elasticity, and collagen contents. The mice exposed to UVB had markedly greater epidermal thickness, TEWL, and skin roughness than those of the normal control (NC) group. In addition, the levels of collagen, skin moisture, and dermal elasticity were lower in the UVB radiation group than the NC group. These UVB-induced skin aging parameters were significantly lower in the groups administered FAMCGSs than in the groups not administered FAMCGSs (p < 0.05). These results show that FAMCGSs exhibit a photoprotective effect in mice exposed to UVB and suggest that FAMCGSs can be used as a food that promotes inner beauty and protects skin from UVB-induced photoaging.

Fermented Aloe arborescens Miller Leaf Extract Suppresses Acute Alcoholic Liver Injury via Antioxidant and Anti-Inflammatory Effects in C57BL/6J Mice.

This study confirmed the change in functional composition and alcohol-induced acute liver injury in Aloe arborescens after fermentation. An acute liver injury was induced by administration of ethanol (3 g/kg/day) to C57BL/6J mice for 5 days. A fermented A. arborescens Miller leaf (FAAL) extract was orally administered 30 minutes before ethanol treatment. After fermentation, the emodin content was approximately 13 times higher than that of the raw material. FAAL extract significantly attenuated ethanol-induced aspartate aminotransferase, alanine aminotransferase, and triglyceride increases in serum and liver tissue. Histological analysis revealed that FAAL extract inhibits inflammatory cell infiltration and fat accumulation in liver tissues. The cytochrome P450 2E1, superoxide dismutase, and glutathione (GSH), which involved in alcohol-induced oxidative stress, were effectively regulated by FAAL extract in serum and liver tissues, except for GSH. FAAL also maintained the antioxidant defense system by upregulating heme oxygenase 1 and nuclear factor erythroid 2-related factor 2 protein expression. In addition, FAAL extract inhibited the decrease in alcohol dehydrogenase and aldehyde dehydrogenase activity, which promoted alcohol metabolism and prevented the activation of inflammatory response. Our results suggest that FAAL could be used as a potential therapeutic agent for ethanol-induced acute liver injury.

Changes in Chemical Compositions and Antioxidant Activities from Fresh to Fermented Red Mountain-Cultivated Ginseng.

This study investigated changes in nutrients (fatty acids, amino acids, and minerals), ginsenosides, and volatile flavors, and antioxidant activities during food processing of mountain-cultivated ginseng (MCG) with the cocktail lactic acid bacteria. Fatty acid content increased, but the free amino acid content decreased, and minerals were practically unaffected during processing. Total phenolic and flavonoid contents and maillard reaction products increased markedly according to processing stage. The total ginsenosides levels increased from 31.25 mg/g (DMCG) to 32.36 mg/g (red MCG, RMCG) and then decreased (27.27 mg/g, at fermented RMCG) during processing. Particularly, the contents of F2 (0.31 → 1.02 → 2.27 mg/g), Rg3 (0.36 → 0.77 → 1.93 mg/g), and compound K (0.5 → 1.68 → 4.13 mg/g) of ginsenosides and ß-panasinsene (17.28 → 22.69 → 31.61%), biocycloelemene (0.11 → 0.84 → 0.92%), δ-cadinene (0.39 → 0.5 → 0.94%), and alloaromadendrene (1.64 → 1.39 → 2.6%) of volatile flavor compounds increased during processing, along with to the antioxidant effects (such as DPPH, ABTS, and hydroxyl radical scavenging activities, and FRAP). This study may provide several choices for the use of ginseng in functional foods and functional cosmetics.

Comprehensive Comparison of Chemical Composition and Antioxidant Activity of Panax ginseng Sprouts by Different Cultivation Systems in a Plant Factory.

In this study, the primary (such as amino acids, fatty acids, and minerals) and secondary (including ginsenosides, phenolic acids, and flavonols) metabolites and antioxidant effects of Panax ginseng sprouts (PGSs) by different cultivation systems, such as soil-substrate cultivation (SSC) and deep-water cultivation (DWC), in a plant factory has been observed. There was no significant difference in the total fatty acid (FA) contents. Particularly, the major FAs of PGSs were palmitic acid (207.4 mg/100 g) of saturated FAs and linoleic acid (397.6 mg/100 g) and α-linolenic acid (222.6 mg/100 g) of unsaturated FAs in the SSC system. The values of total amino acids were all higher in SSC than in DWC. In the case of ginsenosides, the total protopanaxtriol product was 30.88 mg/g in SSC, while the total protopanaxdiol product was 34.83 mg/g in DWC. In particular, the values of total phenolic acids and total flavonols were 133.36 and 388.19 ug/g, respectively, and SSC had a higher content than DWC. In conclusion, the SSC system was shown to be higher in nutritional constituents and antioxidant activities in soil cultivation, suggesting that PGS with SSC has a positive effect on the quality of PGS in a plant factory.

Increased Production of Ginsenoside Compound K by Optimizing the Feeding of American Ginseng Extract during Fermentation by Aspergillus tubingensis.

The ginsenoside compound K (C-K) is widely used in traditional medicines, nutritional supplements, and cosmetics owing to its diverse pharmacological activities. Although many studies on C-K production have been conducted, fermentation is reported to produce C-K with low concentration and productivity. In the present study, addition of an inducer and optimization of the carbon and nitrogen sources in the medium were performed using response surface methodology to increase the C-K production via fermentation by Aspergillus tubingensis, a generally recognized as safe fungus. The optimized inducer and carbon and nitrogen sources were 2 g/l rice straw, 10 g/l sucrose, and 10 g/l soy protein concentrate, respectively, and they resulted in a 3.1-fold increase in the concentration and productivity of C-K (0.22 g/l and 1.52 mg/l/h, respectively) compared to those used before optimization without inducer (0.071 g/l and 0.49 mg/l/h, respectively). The feeding methods of American ginseng extract (AGE), including feeding timing, feeding concentration, and feeding frequency, were also optimized. Under the optimized conditions, A. tubingensis produced 3.96 mM (2.47 g/l) C-K at 144 h by feeding two times with 8 g/l AGE at 48 and 60 h, with a productivity of 17.1 mg/l/h. The concentration and productivity of C-K after optimization of feeding methods were 11-fold higher than those before the optimization (0.22 g/l and 1.52 mg/l/h, respectively). Thus, the optimization for the feeding methods of ginseng extract is an efficient strategy to increase C-K production. To our knowledge, this is the highest reported C-K concentration and productivity via fermentation reported so far.

Hot-melt extruded copper sulfate affects the growth performance, meat quality, and copper bioavailability of broiler chickens.

OBJECTIVE: This study was conducted to evaluate the effects of the supplementation of diets of broiler chickens with hot-melt extruded CuSO4 (HME-Cu) on their growth performance, nutrient digestibility, gut microbiota, small intestinal morphology, meat quality, and copper (Cu) bioavailability. METHODS: A total of 225 broilers (Ross 308), one-day old and initial weight 39.14 g, were weighed and distributed between 15 cages (15 birds per cage) in a completely randomized experimental design with 3 treatments (diets) and 5 replicates per treatment. Cages were allotted to three treatments including control (without supplemental Cu), IN-Cu (16 mg/kg of CuSO4), and HME-Cu (16 mg/kg of HME processed CuSO4). RESULTS: The HME-Cu treatment tended to increase the overall body weight gain (p<0.10). The apparent digestibility of Cu was increased by supplementation of HME-Cu at phase 2 (p<0.05). The Escherichia coli count in cecum tended to decrease with the supplementation with Cu (p<0.10). In addition, the HME-Cu treatment had a higher pH of breast meat than the control and IN-Cu treatments (p<0.05). Significant increases in the cooking loss, water-holding capacity, and lightness in the breast were observed in the HME-Cu treatment compared to the control (p<0.05). The Cu content of excreta increased with the Cu supplementation (p<0.05). The concentration of excreta Cu in broilers was decreased in the HME-Cu compared to the IN-Cu in phase 2 (p<0.05). The Cu concentration in the liver was increased with the HME-Cu supplementation, compared with the control diets (p<0.05). CONCLUSION: This study showed that HME-Cu supplementation at the requirement level (16 mg/kg diets) in broiler diets did not affect the growth performance and the physiological function of Cu in broilers. However, supplementation of Cu in HME form improved the meat quality and the bioavailability of Cu.

Immunomodulatory and anti-inflammatory effects of Phellinus linteus mycelium.

BACKGROUND: The present study extensively aimed to evaluate the underlying mechanism of the immunomodulatory and anti-inflammatory effects of Phellinus linteus mycelium (PLM). METHODS: To assess whether PLM influences the production of markers related to inflammation, Lipopolysaccharide (LPS)-stimulated RAW264.7 cells were treated with PLM (50, 100, 200, and 500 µg/mL). Splenocyte, thymus, peritoneal exudate cells (PEC), and peripheral blood mononuclear cells (PBMC) were isolated from the Balb/c mice treated with Korean red ginseng or PLM once a day for 5 weeks. Moreover, all mice except normal mice were stimulated with 10% proteose peptone (PP) treated 3 days before the sacrifice and 2% starch treated 2 days before the sacrifice. Subsequently, the cytotropic substance was evaluated by using flow cytometry analysis and ELISA assay. RESULTS: PLM200 treatment significantly suppressed the production of nitric oxide (NO) and prostaglandin E2 (PGE2) and inhibited the release of proinflammatory cytokines such as interleukin (IL)-6, IL-1ß, and tumor necrosis factor (TNF)-α dose-dependently in the LPS-stimulated RAW264.7 cells. PLM200 supplementation showed a significant increase in IL-2, IL-12, and interferon (IFN)-γ production and upregulated the ratio of IFN-γ (T-helper type 1, Th1) to IL-4 (T-helper type 2, Th2) in splenocytes. After PLM200 treatment, the significant elevation of CD4+CD25+, CD4+&CD8+, and CD4+CD69+ treatment were detected in thymus. Moreover, CD4+ and CD4+CD69+ in PBMC and CD69+ in PEC were also shown in a significant increase. CONCLUSIONS: Taken together, these results showed an immunomodulatory effect of PLM about an elevated INF-γ/IL4 ratio, as an index of Th1/Th2, as well as the anti-inflammatory effect in the LPS-stimulated RAW264.7 cells. Therefore, our findings demonstrate that PLM possesses immunostimulatory and anti-inflammatory effects.

(-)-Loliolide Isolated from Sargassum horneri Abate UVB-Induced Oxidative Damage in Human Dermal Fibroblasts and Subside ECM Degradation.

Ultraviolet (UV) B exposure is a prominent cause of skin aging and a contemporary subject of interest. The effects are progressing through the generation of reactive oxygen species (ROS) that alter cell signaling pathways related to inflammatory responses. The present study evaluates the protective effects of (7aR)-6-hydroxy-4,4,7a-trimethyl-6,7-dihydro-5H-1-benzofuran-2-one (HTT) isolated from the edible brown algae Sargassum horneri against UVB protective effects in human dermal fibroblasts (HDFs). HTT treatment dose-dependently suppressed intracellular ROS generation in HDFs with an IC50 of 62.43 ± 3.22 µM. HTT abated UVB-induced mitochondrial hyperpolarization and apoptotic body formation. Furthermore, UVB-induced activation of key nuclear factor (NF)-κB and mitogen-activated protein kinase signaling proteins were suppressed in HTT treated cells while downregulating pro-inflammatory cytokines (interleukin-1ß, 6, 8, 33 and tumor necrosis factor-α). Moreover, HTT treatment downregulated matrix metalloproteinase1, 2, 3, 8, 9 and 13 that was further confirmed by the inhibition of collagenase and elastase activity. The evidence implies that HTT delivers protective effects against premature skin aging caused by UVB exposure via suppressing inflammatory responses and degradation of extracellular matrix (ECM) components. Extensive research in this regard will raise perspectives for using HTT as an ingredient in UV protective ointments.

Beneficial Effect of Taraxacum coreanum Nakai via the Activation of LKB1-AMPK Signaling Pathway on Obesity.

OBJECTIVE: Liver kinase B (LKB) 1 and AMP-activated protein kinase (AMPK) are master regulators and sensors for energy homeostasis. AMPK is mainly activated via phosphorylation of LKB1 under energy stress. Here, we highlighted the antiobesity effect and underlying mechanism of Taraxacum coreanum Nakai (TCN) in connection with LKB1-AMPK signaling pathway. METHODS: Male C57BL/6 mice were fed on a high-fat diet (60% kcal fat; HFD) to induce obesity. Simultaneously, they received 100 or 200 mg/kg TCN orally for 5 weeks. We measured the body weight gain and liver weight along with liver histology. Moreover, the changes of factors related to lipid metabolism and ß-oxidation were analyzed in the liver, together with blood parameters. RESULTS: The body weights were decreased in mice of the TCN200 group more than those of the HFD control group. Moreover, TCN supplementation lowered serum triglyceride (TG) and total cholesterol (TC) levels, whereas TCN increased HDL-cholesterol level. Liver pathological damage induced by HFD was alleviated with TCN treatment and accompanied with significant reduction in serum AST and ALT activities. In addition, TCN significantly increased the expression of p-AMPK compared with the HFD control group via the activation of LKB1/AMPK signaling pathway. Lipid synthesis gene like ACC was downregulated and factors related to ß-oxidation such as carnitine palmitoyl transferase-1 (CPT-1) and uncoupling protein 2 (UCP-2) were upregulated through peroxisome proliferator-activated receptor (PPAR) α activation. CONCLUSION: Taken together, these data suggest that TCN treatment regulates lipid metabolism via LKB1-AMPK signaling pathway and promotes ß-oxidation by PPARα; hence, TCN may have potential remedy in the prevention and treatment of obesity.

Protective Effects of Inflammation of Curcumae Longae Rhizoma 30% EtOH Extract on Acute Reflux Esophagitis Rats.

Gastroesophageal reflux disease (GERD) is induced by the reflux of stomach contents or gastric acid, pepsin into the esophagus for prolonged periods of time due to defection of the lower esophageal sphincter. Reflux esophagitis is a disease found in less than 50% of GERD patients. This study is aimed at evaluating the protective effect of Curcumae longae Rhizoma 30% EtOH extract (CLR) in acute reflux esophagitis (ARE) rats. CLR measured antioxidant activity through in vitro experiments. Based on the results, we performed experiments in vivo. Before 90 min ARE induction, CLR was administered orally by concentration. ARE was derived by linking the metastatic junction between pylorus and forestomach and corpus in Sprague-Dawley rats. And rats were sacrificed 5 h after surgery. We analyzed the expression of antioxidant and inflammatory-related markers by western blot and observed the production of alanine aminotransferase (ALT), aspartate aminotransferase (AST), reactive oxygen species (ROS), peroxynitrite (ONOO-), and thiobarbituric acid reactive substance (TBARS). The administration of CLR reduced esophagus tissue damage in rats with acute reflux esophagitis and decreased the elevated ALT, AST, ROS, ONOO-, and TBARS. In addition, CLR effectively increased antioxidant-related factors and reduced inflammatory protein. Overall, these results suggest that CLR would be used as a therapeutic material in protection and treatment for ARE. Overall, CLR treatment informed that markedly ameliorated inactivation of NF-κB led to the inhibition of the expressions of proinflammatory proteins. These results suggest that CLR would be used as a therapeutic material in protection and treatment for ARE.

Lycopene Improves In Vitro Development of Porcine Embryos by Reducing Oxidative Stress and Apoptosis.

In vitro culture (IVC) for porcine embryo development is inferior compared to in vivo development because oxidative stress can be induced by the production of excessive reactive oxygen species (ROS) under high oxygen tension in the in vitro environment. To overcome this problem, we investigated the effect of lycopene, an antioxidant carotenoid, on developmental competence and the mechanisms involved in mitochondria-dependent apoptosis pathways in porcine embryos. In vitro fertilized (IVF) embryos were cultured in IVC medium supplemented with 0, 0.02, 0.05, 0.1, or 0.2 µM lycopene. The results indicate that 0.1 µM lycopene significantly increased the rate of blastocyst formation and the total cell numbers, including trophectoderm cell numbers, on Day In terms of mitochondria-dependent apoptosis, IVF embryos treated with 0.1 µM lycopene exhibited significantly decreased levels of ROS, increased mitochondrial membrane potential, and decreased expression of cytochrome c on Days 2 and Furthermore, 0.1 µM lycopene significantly decreased the number and percentage of caspase 3-positive and apoptotic cells in Day-6 blastocysts. In addition, Day-2 embryos and Day-6 blastocysts treated with 0.1 µM lycopene showed significantly reduced mRNA expression related to antioxidant enzymes (SOD1, SOD2, CATALASE) and apoptosis (BAX/BCL2L1 ratio). These results indicate that lycopene supplementation during the entire period of IVC enhanced embryonic development in pigs by regulating oxidative stress and mitochondria-dependent apoptosis.

Protective Effects of Phellinus linteus Mycelium on the Development of Osteoarthritis after Monosodium Iodoacetate Injection.

OBJECTIVE: The aim of this study was to identify the protective effects of Phellinus linteus mycelium (PLM) and its possible mechanisms in a model of monosodium iodoacetate- (MIA-) induced osteoarthritis (OA). METHODS: Intra-articular injection of MIA was injected to 50 µL with 80 mg/mL using a 0.3 mL insulin syringe into the right knee joint. Changes in hindpaw weight-bearing distribution between the right (osteoarthritic) and left (contralateral control) legs were used as an index of joint discomfort. PLM (50, 100, and 200 mg/kg body weight) was orally administered once daily for 14 days from day 7 after MIA treatment. And then, various factors associated with inflammatory response and cartilage degeneration in cartilage tissues detected by western blotting. RESULTS: PLM treatment showed a concentration-dependent elevation in change in hindpaw weight-bearing distribution (HWBD). PLM200 demonstrated the capacity to significantly increase HWBD, indicating that the change in weight-bearing distribution means the reduction of spontaneous pain. Our results indicate that PLM suppressed the inflammatory factors via NF-κB signaling pathway induced by p38 phosporlyation. Moreover, PLM200 exhibited a significant reduction of ROS produced by the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. PLM100 and PLM200 inhibited the levels of matrix metalloproteinase (MMP)-1, one of proteinase that degrades extracellular matrix (ECM). CONCLUSIONS: Taken together, our results indicated that PLM has a strong chondroprotective effect through the suppression both ROS production and inflammation.

Step gradient alcohol precipitation for the purification of low molecular weight fucoidan from Sargassum siliquastrum and its UVB protective effects.

Ultraviolet B (UVB) can induce oxidative damage to outermost layers of skin causing suntans, sunburns, and, in severe cases, blisters leading to photoaging. Low molecular weight (MW) fucoidan is renowned for possessing enhanced antioxidant activities. The present study discloses the use of step gradient ethanol precipitation in refining fucoidan fractions (SSQC1-SSQC4) from Sargassum siliquastrum and evaluation of their UVB-protective effects in human HaCaT keratinocytes. Among the fractions, SSQC4 indicated the best bioactive effects. 1H NMR, FTIR, monosaccharide composition by HPAEC-PAD analysis, MW estimation by agarose gel electrophoresis were used to characterize the fractions. SSQC4 was comprising of fucoidan, with an estimated MW distribution of 8-25 kDa. Exposure of UVB increased intracellular ROS, DNA damage, loss of mitochondrial membrane potential, apoptotic body formation causing cell death through the mitochondria-mediated apoptosis pathway. SSQC4 treatment could dose-dependently attenuate the ROS levels and suppress mitochondria-mediated apoptosis in UVB exposed keratinocytes. SSQC4 treatment enhanced cellular antioxidant defense by increasing Nrf2 mediated HO-1 generation, which was identified as the cause of observed bioactivities. The safety and stability of SSQC4 could be further evaluated to promote its use as a bioactive natural ingredient in UV-protective cosmetics.

Hot melt extruded-based nano zinc as an alternative to the pharmacological dose of ZnO in weanling piglets.

OBJECTIVE: This study was conducted to investigate the effects of hot-melt extruded ZnO nano-particles (HME-ZnO) as an alternative for P-ZnO on growth performance, nutrient digestibility, Zn bioavailability, intestinal microbiota, and intestinal morphology of weanling pigs. METHODS: A total of 450 piglets (Landrace×Yorkshire×Duroc) were randomly allotted to five treatments based on initial body weight and sex. The experimental diets were fed in a meal form as phase 1 from d 0 to 14 and phase 2 from d 15 to 28. Treatments were the control diet without ZnO supplementation, the diet containing 2,500 ppm Zn as ZnO, and three diets containing 500, 1,000, or 2,500 ppm Zn as HME-ZnO. RESULTS: The overall result showed a higher (p<0.01) average daily gain in weanling pigs fed ZnO-supplemented diets in comparison to the control diet. There was a decrease (p<0.01) in fecal score in the ZnO-supplemented diets. Dietary supplementation of ZnO improved (p<0.05) crude protein digestibility. The weanling pigs fed the P-ZnO diet had a lower (p<0.01) Zn digestibility in the feces than HME-ZnO supplemented treatments. Weanling pigs fed diets supplemented with ZnO had greater (p<0.05) Lactobacillus spp. populations and lower Clostridium spp. (p<0.05) and Coliforms (p<0.01) populations in the ileum. Weanling pigs fed diets supplemented with increasing concentrations of HME-ZnO linearly decreased Clostridium spp. (p<0.05) and Coliforms (p<0.01) in the ileum. Lower (p<0.05) Clostridium spp. and Coliforms counts in the colon were observed in pigs fed with ZnO-supplemented diets. Weanling pigs fed diets supplemented with ZnO showed a greater (p<0.01) villus height in the duodenum. CONCLUSION: Dietary supplementation of HME-ZnO and P-ZnO showed a potential to improve the digestibility of protein, intestinal Coliform and Clostridium, villus height in duodenum and ileum. Moreover, HME-ZnO showed a higher Zn digestibility compared with P-ZnO.

Molecular Mechanism of the Protective Effect of Zerumbone on Lipopolysaccharide-Induced Inflammation of THP-1 Cell-Derived Macrophages.

Unregulated inflammatory responses lead to massive production of macrophages-activating inflammatory cytokines and chemokines, which may induce diabetes, cancer, and atherosclerosis. Macrophages differentiated from human monocyte (THP-1) have been extensively used in in vitro inflammation models in recent studies. Zerumbone is a major component of the essential oil of Zingiber zerumbet Smith, a type of wild ginger. In this study, we investigated the effects of zerumbone on the secretion of pro-inflammatory cytokines and its underlying mechanistic regulation in lipopolysaccharide (LPS)-activated inflammation of THP-1 cell-derived macrophages. Nuclear factor (NF)-κB and toll-like receptors (TLRs) are known to play important roles in inflammation and immunity. If pathogens enter the host, TLRs recognize the pathogens and signal for the activation of NF-κB to induce inflammatory gene products, such as cytokines. We demonstrated that zerumbone inhibits the secretion of pro-inflammatory cytokines and the induction of NF-κB p65 in LPS-activated inflammation of THP-1 cell-derived macrophages. In addition, zerumbone significantly inhibited mRNA and protein levels of TLR-2/4, and the expression of myeloid differentiation factor 88 (MyD88) adaptor proteins in the LPS-activated inflammation of THP-1 cell-derived macrophages. Moreover, we showed that zerumbone (1-10 µM) regulated histone deacetylase (HDAC) activity and the expression of HDAC genes. H3K9ac, H3K27ac, and H3K4me2 are inducible histone marks that activate gene expression. Treatment with LPS upregulated H3K9ac, H3K27ac, and H3K4me2 in THP-1 cell-derived macrophages; however, this upregulation was decreased by zerumbone treatment. Therefore, these results provide evidence that zerumbone may have therapeutic benefits for chronic inflammatory diseases.

A phase II study of preoperative chemoradiation with tegafur-uracil plus leucovorin for locally advanced rectal cancer with pharmacogenetic analysis.

BACKGROUND: This study aimed to evaluate the efficacy of a high dose of oral tegafur-uracil (400 mg/m2) plus leucovorin with preoperative chemoradiation of locally advanced rectal cancer and to explore the impact of polymorphisms of cytochrome P 2A6 (CYP2A6), uridine monophosphate synthetase (UMPS), and ATP-binding cassette B1 (ABCB1) on clinical outcome. METHODS: Patients with cT3 or cT4 rectal cancer were enrolled and were given tegafur-uracil 400 mg/m2/day and leucovorin 90 mg/m2/day for 7 days a week during preoperative chemoradiation (50.4 Gy/28 fractions) in this phase II trial. Primary endpoint was pathologic complete response rate, and the secondary endpoint was to explore the association between clinical outcomes and genetic polymorphisms CYP2A6 (*4, *7, *9 and *10), UMPS G638C, and three ABCB1 genotypes (C1236T, C3435T, and G2677T). RESULTS: Ninety-one patients were given study treatment, and 90 underwent surgery. Pathologic complete response was noted in 10 patients (11.1%). There was no grade 4 or 5 toxicity; 20 (22.0%) experienced grade 3 toxicities, including diarrhea (10, 11.0%), abdominal pain (2, 2.2%), and anemia (2, 2.2%). Relapse-free survival and overall survival at 5 years were 88.6% and 94.2%, respectively. Patients with the UMPS 638 CC genotype experienced significantly more frequent grade 2 or 3 diarrhea (p for trend = 0.018). CONCLUSIONS: Preoperative chemoradiation with tegafur-uracil 400 mg/m2/day with leucovorin was feasible, but did not meet the expected pathologic complete response rate. The UMPS 638 CC genotype might be a candidate biomarker predicting toxicity in patients receiving tegafur-uracil/leucovorin-based preoperative chemoradiation for locally advanced rectal cancer. TRIAL REGISTRATION: ISRCTN11812525 , registered on 25 July 2016. Retrospectively registered.

Hyperforin attenuates microglia activation and inhibits p65-Ser276 NFκB phosphorylation in the rat piriform cortex following status epilepticus.

Hyperforin, a lipophilic constituent of medicinal herb St. John's Wort, has neurobiological effects including antidepressant activity, antibiotic potency, anti-inflammatory activity and anti-tumoral properties. Furthermore, hyperforin activates transient receptor potential conical channel-6 (TRPC6), a nonselective cation channel. To elucidate the roles of hyperforin and TRPC6 in neuroinflammation in vivo, we investigated the effect of hyperforin on neuroinflammatory responses and its related events in the rat piriform cortex (PC) following status epilepticus (SE). Hyperforin attenuated microglial activation, p65-serine 276 NFκB phosphorylation, and suppressed TNF-α expression in the PC following SE. Hyperforin also effectively alleviated SE-induced vasogenic edema formation, neuronal damage, microglial TRPC6 induction and blood-derived monocyte infiltration. Our findings suggest that hyperforin may effectively attenuate microglia-mediated neuroinflammation in the TRPC6-independent manner.

Hepatoprotective effects of fermented field water-dropwort (Oenanthe javanica) extract and its major constituents.

Dropwort (Oenanthe javanica) has been used for many years for the treatment of inflammatory conditions, including hepatitis. We investigated the protective effects of fermented field water-dropwort extract (FDE) on tert-butyl hydroperoxide (t-BHP)-induced hepatotoxicity in HepG2 cells and carbon tetrachloride (CCl4)-induced liver damage in rats. Pretreatment with FDE prior to the t-BHP treatment of HepG2 cells inhibited cell death and lactate dehydrogenase (LDH) leakage in a dose-dependent manner. In addition FDE significantly prevented the increase of hepatic enzyme markers (ALT, AST) in vivo. Moreover, FDE administration for 7 days significantly affected CYP2E1, CYP4A2, and PPARγ gene expressions. CYP2E1 and CYP4A2 gene expression in the liver, increased 2 and 22-fold by CCl4 administration, respectively, was attenuated to normal levels by pretreatment with FDE. PPARγ gene expression, completely blocked by CCl4 treatment, was increased by FDE pretreatment compared to normal control group. Histopathological examination of the livers also revealed that FDE reduced the incidence of liver lesions. Caffeic acid and chlorogenic acid were identified as major constituents of FDE. These results demonstrate the protective effects of FDE against hepatocytotoxicity induced by CCl4 and t-BHP in rats and HepG2 cells, thus indicating the potential of FDE as a therapeutic for acute liver diseases.

Acidic polysaccharide of Panax ginseng regulates the mitochondria/caspase-dependent apoptotic pathway in radiation-induced damage to the jejunum in mice.

Owing to its susceptibility to radiation, the small intestine of mice is valuable for studying radioprotective effects. When exposed to radiation, intestinal crypt cells immediately go through apoptosis, which impairs swift differentiation necessary for the regeneration of intestinal villi. Our previous studies have elucidated that acidic polysaccharide of Panax ginseng (APG) protects the mouse small intestine from radiation-induced damage by lengthening villi with proliferation and repopulation of crypt cells. In the present study, we identified the molecular mechanism involved. C57BL/6 mice were irradiated with gamma-rays with or without APG and the expression levels of apoptosis-related molecules in the jejunum were investigated using immunohistochemistry. APG pretreatment strongly decreased the radiation-induced apoptosis in the jejunum. It increased the expression levels of anti-apoptotic proteins (Bcl-2 and Bcl-XS/L) and dramatically reduced the expression levels of pro-apoptotic proteins (p53, BAX, cytochrome c and caspase-3). Therefore, APG attenuated the apoptosis through the intrinsic pathway, which is controlled by p53 and Bcl-2 family members. Results presented in this study suggest that APG protects the mouse small intestine from irradiation-induced apoptosis through inhibition of the p53-dependent pathway and the mitochondria/caspase pathway. Thus, APG may be a potential agent for preventing radiation induced injuries in intestinal cells during radio-therapy such as in cancer treatment.