Diabetes mellitus (DM) is one of the main global health problems. Chronic exposure to hyperglycemia can lead to cellular dysfunction that may become irreversible over time, a process that is termed glucose toxicity. Our perspective about glucose toxicity as it pertains to the pancreatic β-cell is that the characteristic decreases in insulin secretion are caused by regulated apoptotic gene expression. In this study, we examined whether ferulic acid protects INS-1 pancreatic cells against high glucose-induced apoptosis. High glucose concentration (30 mM) induced glucotoxicity and death of INS-1 pancreatic β cells. However, treatment with 1, 5, 10, or 20 μM ferulic acid increased the cell viability in a concentration-dependent manner. Treatment with ferulic acid dose-dependently decreased the intracellular levels of reactive oxygen species, thiobarbituric acid reactive substances, and nitric oxide in INS-1 pancreatic β cells pretreated with high glucose. These effects influence the apoptotic pathway, increasing the expression of the anti-apoptotic protein Bcl-2 and reducing the levels of pro-apoptotic proteins, including Bax, cytochrome C, and caspase 9. Annexin V/propidium iodide staining indicated that ferulic acid significantly reduced high glucose-induced apoptosis. These results demonstrate that ferulic acid is a potential therapeutic agent to protect INS-1 pancreatic β cells against high glucose-induced apoptosis.
Jinshun Zhan;Zhiyong Gu;Haibo Wang;Yuhang Liu;Yanping Wu;Junhong Huo
Animal Bioscience
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v.37
no.2
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pp.303-314
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2024
Objective: Rutin, also called vitamin P, is a flavonoids from plants. Previous studies have indicated that rutin can alleviate the injury of tissues and cells by inhibiting oxidative stress and ameliorating inflammation. There is no report on the protective effects of rutin on goat rumen epithelial cells (GRECs) at present. Hence, we investigated whether rutin can alleviate lipopolysaccharide (LPS)-induced damage in GRECs. Methods: GRECs were cultured in basal medium or basal medium containing 1 ㎍/mL LPS, or 1 ㎍/mL LPS and 20 ㎍/mL rutin. Six replicates were performed for each group. After 3-h culture, the GRECs were harvested to detect the relevant parameters. Results: Rutin significantly enhanced the cell activity (p<0.05) and transepithelial electrical resistance (TEER) (p<0.01) and significantly reduced the apoptosis rate (p<0.05) of LPS-induced GRECs. Rutin significantly increased superoxide dismutase, glutathione peroxidase, and catalase activity (p<0.01) and significantly decreased lactate dehydrogenase activity and reactive oxygen species and malondialdehyde (MDA) levels in LPS-induced GRECs (p<0.01). The mRNA and protein levels of interleukin 6 (IL-6), IL-1β, and C-X-C motif chemokine ligand 8 (CXCL8) and the mRNA level of tumor necrosis factor-α (TNF-α) and chemokine C-C motif ligand 5 (CCL5) were significantly increased in LPS-induced GRECs (p<0.05 or p<0.01), while rutin supplementation significantly decreased the mRNA and protein levels of IL-6, TNF-α, and CXCL8 in LPS-induced GRECs (p<0.05 or p<0.01). The mRNA level of toll-like receptor 2 (TLR2), and the mRNA and protein levels of TLR4 and nuclear factor κB (NF-κB) was significantly improved in LPS-induced GRECs (p<0.05 or p<0.01), whereas rutin supplementation could significantly reduce the mRNA and protein levels of TLR4 (p<0.05 or p<0.01). In addition, rutin had a tendency of decreasing the protein levels of CXCL6, NF-κB, and inhibitor of nuclear factor kappa-B alpha (0.05
Hong Kyu Lee;Yun-Jung Na;Su-Min Seong;Dohee Ahn;Kyung-Chul Choi
Biomolecules & Therapeutics
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v.32
no.3
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pp.368-378
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2024
Cordycepin, a valuable bioactive component isolated from Cordyceps militaris, has been reported to possess anti-cancer potential and the property to enhance the effects of chemotherapeutic agents in various types of cancers. However, the ability of cordycepin to chemosensitize cholangiocarcinoma (CCA) cells to gemcitabine has not yet been evaluated. The current study was performed to evaluate the above, and the mechanisms associated with it. The study analyzed the effects of cordycepin in combination with gemcitabine on the cancer stem-like properties of the CCA SNU478 cell line, including its anti-apoptotic, migratory, and antioxidant effects. In addition, the combination of cordycepin and gemcitabine was evaluated in the CCA xenograft model. The cordycepin treatment significantly decreased SNU478 cell viability and, in combination with gemcitabine, additively reduced cell viability. The cordycepin and gemcitabine co-treatment significantly increased the Annexin V+ population and downregulated B-cell lymphoma 2 (Bcl-2) expression, suggesting that the decreased cell viability in the cordycepin+gemcitabine group may result from an increase in apoptotic death. In addition, the cordycepin and gemcitabine co-treatment significantly reduced the migratory ability of SNU478 cells in the wound healing and trans-well migration assays. It was observed that the cordycepin and gemcitabine cotreatment reduced the CD44highCD133high population in SNU478 cells and the expression level of sex determining region Y-box 2 (Sox-2), indicating the downregulation of the cancer stem-like population. Cordycepin also enhanced oxidative damage mediated by gemcitabine in MitoSOX staining associated with the upregulated Kelch like ECH Associated Protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) expression ratio. In the SNU478 xenograft model, co-administration of cordycepin and gemcitabine additively delayed tumor growth. These results indicate that cordycepin potentiates the chemotherapeutic property of gemcitabine against CCA, which results from the downregulation of its cancer-stem-like properties. Hence, the combination therapy of cordycepin and gemcitabine may be a promising therapeutic strategy in the treatment of CCA.
The extrusion-cooking condition on Cordyceps pruinosa was designed using twin-screw extruder. Response surface methodology (RSM) was used to investigate extrusion-cooking using a central composition design with varying die temperature $(114-146^{\circ}C)$, feed moisture $(22-38\%)$, feed rate (4-14 ka/h) and screw speed (120-280 rpm). System parameters (die pressure and specific mechanical energy (SME)) and extrudate parameters (density and water solubility index (WSI)) were statically analyzed using RSH. Die pressure was significantly affected by temperature, moisture contents and feed rate. SM was affected by screw speed and feed rate. When die temperature is $130^{\circ}C$ and moisture content $25\%$, the optimum pressure is shown. SME is about 20 Wh/kg, when feed rate is $10\~12kg/min$ and screw speed $200\~250rpm$. WSI was affected by temperature and moisture contents. Density was not affected by any factor. WSI increases by $7\%$ from about $23\%$ to about $30\%$, as temperature is raised from $120^{\circ}C\;to\;140^{\circ}C$. The WSI of Cordyceps pruinosa pulverized after extruding (PE) is about $26.97\%$ higher than that of raw material and $10\%$ higher than that of pulverized after drying (PD). The content of unsaturated fatty acid were not significantly different in PD and PE. Anti-oxidative activity of PE was 1.67-2.2 times higher than that of PD in Cordyceps pruinosa using 1- dipheny1-2-picrylhydrazyl method (DPPH).
In order to examine the effect of Injinhotang extract on the liver cancer induced by N-nitrosodiethylamine (NDEA) and carbon tetrachloride ($CCl_4$) in Rats. The animals were divided into three groups. The normal (Nor) group were fed basal diet. Control (Con) group were administered with NDEA (200 mg/kgb.w., i.p.) and $CCl_4$. Injinhotang extract (IJH) group treated with Injinhotang extract (260 mg/kg/day) for 8 weeks after NDEA+$CCl_4$. Enzymic antioxidants, such as superoxide dismutase (SOD) and catalase levels were determined in all the groups of animals. The activities of SOD were significantly increased in the Con, but the activities of catalase were decreased in the Con, but the anti-oxidative enzyme activities of superoxide dismutase and catalase were increased in the IJH. In the immunohistochemistry observation, treatment of Injinhotang extract reduced the rates of p53 immunoreactivity. According to the electron microscopical observation, in the liver cancer cells were increased the smooth endoplasmic reticulum and dilated the rough endoplasmic reticulum in the Con compared with IJH. These results suggest that administration of Injinhotang extract suppress or retard NDEA and $CCl_4$-induced liver cancer.
Matrix metalloproteinases (MMPs) are crucial extracellular matrices degrading enzymes that take important roles in metastasis of cancer progression as well as other significant conditions such as oxidative stress and hepatic fibrosis. Natural products are on the rise for their potential to provide remarkable health benefits. In this context, halophytes have been of interest in the nutraceutical field with reported instances of isolation of bioactive compounds. In this study, Limonium tetragonum, an edible halophyte, was studied for its ability to inhibit MMP-2 and -9 using HT1080 fibrosarcoma cells. Results showed that L. tetragonum extract was able to inhibit the enzymatic activity and mRNA expression of MMP-2 and -9 according to gelatin zymography and RT-PCR assays, respectively, but it was not able to significantly change the MMP pathway related factors such as tissue inhibitors of metalloproteinases. Also, Mitogen-activated protein kinases pathway-related protein levels and their phosphorylation were assayed. While the phosphorylated p38 levels were decreased, extracellular signal-regulated kinase and c-Jun N-terminal kinase were not affected by L. tetragonum treatment. In conclusion, it was suggested that L. tetragonum contains substances acting as MMP inhibitors on enzymatic activity rather than intracellular pathway intervention, which could be useful for further utilization of L. tetragonum as a source for anti-MMP agents.
Objectives : In this study, the antioxidant activities of the 80% ethanol and hot water extracts of Euphorbia supina Rafinesque were investigated. Methods : We measured total phenol contents, flavonoid contents, 2,2-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging assay, 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) radical scavenging assay. The production of reactive oxygen species was measured in LPS-induced RAW 264.7 cells using flow cytometry system. Results : The content of phenol in the hot water extract was $65.529{\pm}0.462mg/g$ and $126.932{\pm}1.894mg/g$ in the 80% ethanol extract, and that of flavonoid in the hot water extract was $16.063{\pm}0.471mg/g$ and $29.159{\pm}1.963mg/g$ in the ethanol extract. The 80% ethanol extract also showed higher DPPH and ABTS radical scavenging activities ($90.8{\pm}1.0%$ and $92.5{\pm}0.7%$) than the hot water extract ($81.5{\pm}0.5%$ and $91.5{\pm}0.2%$). The production of reactive oxygen species(ROS) was reduced dose-dependently by 80% ethanol and hot water extract at concentration of 1, 10 and $100{\mu}g/m{\ell}$ of RAW 264.7 cells. Conclusion : According to these results, the 80% ethanol extract of Euphorbia supina Rafinesque has a good anti-oxidative effects than the hot water extract. Thus, the 80% ethanol extract of Euphorbia supina Rafinesque may serve as useful natural antioxidants.
In this study, the effects of propolis and vitamin C (L-ascorbic acid) supplementation in diets were investigated on feed intake (FI), body weight (BW), body weight gain (BWG), feed conversion rate (FCR) and digestibility and on egg production and qualities (weight, mortality, shell thickness) in laying hens exposed to heat stress. A total of 150 Hyline White Leghorn, aged 42 weeks, hens was divided into five groups of 30 hens. Chicks were randomly divided into 1 positive control, 1 control and 3 treatment groups. The chicks were kept in cages in temperature-controlled rooms at $22^{\circ}C$ for 24 h/d (positive control, Thermoneutral, TN group) or $34^{\circ}C$ for 9 h/d from 08.00-17.00 h followed by $22^{\circ}C$ for 15 h (control, heat stress, HS group) and fed a basal diet or basal diet supplemented with vitamin C (250 mg/kg of L- ascorbic acid/kg of diet) or two levels of propolis (2 and 5 g of ethanol extracted propolis/kg of diet). Increased FI (p<0.05) and improvement in FCR (p<0.05), hen day egg (p<0.05) and egg weight (p<0.05) were found in Vitamin C and propolis-supplemented laying hens reared under heat stress conditions. Mortality rate was higher in the control group than TN, vitamin C and propolis groups (p<0.05). Digestibility of dry matter, organic matter, crude protein and ether extract improved with increasing of both dietary vitamin C and propolis (p<0.05). Vitamin C or propolis supplementation did not affect either the percentage shape index, yolk index or haugh unit and albumen index (p>0.05). However, the egg shell thickness and egg shell weight appeared to be increased in Vitamin C and propolis groups in comparison to HS group birds (p<0.05). In conclusion, dietary supplementation of laying hens with anti-oxidants (vitamin C and propolis) can attenuate heat stress-induced oxidative damage. These positive effects were evidenced by increased growth performance and digestibility, improvement of egg shell thickness and egg weight in comparison to non-supplemented birds. Moreover, supplementation with propolis (5 g/kg diet) was the most efficient treatment.
Fifty-six [(Duroc${\times}$Yorkshire)${\times}$Landrace] pigs with an average initial BW of 19.3${\pm}$0.17 kg were used in this 15-wk growth experiment to investigate the effects of grape pomace fermented by Saccharomyces boulardii on pig growth performance, nutrient digestibility and quality attributes of pork. Pigs were allotted to 2 dietary treatments (7 replications) based on their initial BW in a randomized complete block design. The experimental treatments were: i) control (CON; basal diet), ii) FGPP (CON+30 g/kg fermented grape pomace product). Dietary FGPP improved (p<0.05) average daily gain (ADG), coefficient apparent total tract digestibility (CATTD) of dry matter (DM) and nitrogen (N) during 35-70 d of the experiment. Similarly, pigs fed the FGPP supplemented diet had a higher N digestibility (p<0.05) in the finisher phase (day 71-105). Dietary FGPP increased (p<0.05) the marbling score, the redness ($a^*$) and yellowness ($b^*$) values, as well as the anti-oxidative ability (lower TBARS). The inclusion of FGPP reduced palmitic acid (C:16:0), stearic acid (C:18:0), arachidic acid (C:20:0) and SFA levels (p<0.05) in subcutaneous fat. An increased (p<0.05) linoleic acid (C18:2n6), total PUFA and PUFA/SFA ratio were observed in the FGPP group. Dietary FGPP supplementation decreased the arachidic acid (C:20:0) level in longissimus muscle (LM). In conclusion, dietary inclusion of FGPP at the level of 30 g/kg improved the growth performance, nutrients digestibility and altered the fatty acid pattern in the subcutaneous fat as well as some attributes of pork meat.
Kim, Seong Ryul;Kim, Kee-Young;Kim, Seong-Wan;Park, Seung-Won
International Journal of Industrial Entomology and Biomaterials
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v.40
no.1
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pp.16-21
/
2020
Humans use insects as food and traditional medicine for many years. Hemolymph is the circulating fluid of insects and is a key component of their immune system. However, limited information is available regarding hemolymph identification, development, and differentiation, as well as the related cellular immune responses. In a previous study, hemolymph extracts prepared from Bombyx mori larvae were found to exert anti-inflammatory effects. In this study, we aimed to identify and compare the antioxidant activity of immune-challenged and unchallenged B. mori hemolymph extracts in vitro. For this purpose, human epithelial Caco-2 cells were first exposed to oxidative stress and then treated with various concentrations and incubation times of either immune-challenged or unchallenged B. mori hemolymph extracts. Next, we determined the effect of treatment on the relative expression of GPX-1, SOD-1, and SOD-2 antioxidant marker genes. We found that the expression rates of the three marker genes were markedly higher at a immune-challenged hemolymph extract concentration of 80 ppm compared to those at other concentrations, and the antioxidant effects were enhanced after treatment for 48 hr. Thus, B. mori hemolymph extracts showed antioxidant activity within the limited time and dose. Especially, the immune-challenged B. mori hemolymph extracts showed higher the antioxidant activities than unchallenged one. The activity of silkworm hemolymph extracts could facilitate the development of new types of functional foods, feed additives, and biomaterials with antioxidant properties.
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