• Nutrition Research and Practice
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• v.16 no.5
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• pp.549-564
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• 2022

BACKGROUND/OBJECTIVES: Oxidative stress is caused by an imbalance between harmful free radicals and antioxidants. Long-term oxidative stress can lead to an "exhausted" status of antioxidant defense system triggering development of metabolic syndrome and chronic inflammation. Green perilla (Perilla frutescens) is commonly used in Asian cuisines and traditional medicine in southeast Asia. Green perilla possesses numerous beneficial effects including anti-inflammatory and antioxidant functions. To investigate the potentials of green perilla leaf extract (PE) on oxidative stress, we induced oxidative stress by high-fat diet (HFD) in aging mice. MATERIALS/METHODS: C57BL/6J male mice were fed HFD continuously for 53 weeks. Then, mice were divided into three groups for 12 weeks: a normal diet fed reference group (NDcon), high-fat diet fed group (HDcon), and high-fat diet PE treated group (HDPE, 400 mg/kg of body weight). Biochemical analyses of serum and liver tissues were performed to assess metabolic and inflammatory damage and oxidative status. Hepatic gene expression of oxidative stress and inflammation related enzymes were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: PE improved hepatopathology. PE also improved the lipid profiles and antioxidant enzymes, including hepatic glutathione peroxidase (GPx) and superoxide dismutase (SOD) and catalase (CAT) in serum and liver. Hepatic gene expressions of antioxidant and anti-inflammatory related enzymes, such as SOD-1, CAT, interleukin 4 (IL-4) and nuclear factor erythroid 2-related factor (Nrf2) were significantly enhanced by PE. PE also reduced the levels of hydrogen peroxide (H₂O₂) and malondialdehyde (MDA) in the serum and liver; moreover, PE suppressed hepatic gene expression involved in pro-inflammatory response; Cyclooxygenase-2 (COX-2), nitric oxide synthase (NOS), interleukin 1 beta (IL-1β), and interleukin 6 (IL-6). CONCLUSIONS: This research opens opportunities for further investigations of PE as a functional food and possible anti-aging agent due to its attenuative effects against oxidative stress, resulting from HFD and aging in the future.

• Journal of Ginseng Research
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• v.47 no.1
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• pp.106-116
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• 2023

Background: Pirarubicin (THP) is an anthracycline antibiotic used to treat various malignancies in humans. The clinical usefulness of THP is unfortunately limited by its dose-related cardiotoxicity. Ginsenoside F1 (GF1) is a metabolite formed when the ginsenosides Re and Rg1 are hydrolyzed. However, the protective effects and underlying mechanisms of GF1 on THP-induced cardiotoxicity remain unclear. Methods: We investigated the anti-apoptotic and anti-oxidative stress effects of GF1 on an in vitro model, using H9c2 cells stimulated by THP, plus trigonelline or AKT inhibitor imidazoquinoxaline (IMQ), as well as an in vivo model using THP-induced cardiotoxicity in rats. Using an enzyme-linked immunosorbent test, the levels of malondialdehyde (MDA), brain natriuretic peptide (BNP), creatine kinase (CK-MB), cardiac troponin (c-TnT), lactate dehydrogenase (LDH), superoxide dismutase (SOD) and glutathione (GSH) were determined. Nuclear factor (erythroid-derived2)-like 2 (Nrf2) and the expression of Nrf2 target genes, including heme oxygenase-1 (HO-1), glutathione-S-transferase (Gst), glutamate-cysteine ligase modifier subunit (GCLM), and expression levels of AKT/Bcl-2 signaling pathway proteins were detected using Western blot analysis. Results: THP-induced myocardial histopathological damage, electrocardiogram (ECG) abnormalities, and cardiac dysfunction were reduced in vivo by GF1. GF1 also decreased MDA, BNP, CK-MB, c-TnT, and LDH levels in the serum, while raising SOD and GSH levels. GF1 boosted Nrf2 nuclear translocation and Nrf2 target gene expression, including HO-1, Gst, and GCLM. Furthermore, GF1 regulated apoptosis by activating AKT/Bcl-2 signaling pathways. Employing Nrf2 inhibitor trigonelline and AKT inhibitor IMQ revealed that GF1 lacked antioxidant and anti-apoptotic effects. Conclusion: In conclusion, GF1 was found to alleviate THP-induced cardiotoxicity via modulating Nrf2 and AKT/Bcl-2 signaling pathways, ultimately alleviating myocardial oxidative stress and apoptosis.

• Herbal Formula Science
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• v.31 no.1
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• pp.53-65
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• 2023

Objectives : Present study investigated the hepatoprotective effects and the optimal mixing ratio of fermented Schizandrae Fructus Pomace (fSFP) and Hoveniae Semen Cum Fructus (HSCF) extract combination in carbon tetrachloride (CCl₄)-induced acute liver injury mice. Methods : ICR mice were orally administered with 200 mg/kg of fSFP, HSCF and mixtures of fSFP and HSCF [MSH (w:w); 1:1, 1:2, 1:4, 1:6, 2:1, 4:1, 6:1, and 8:1] for 7 consecutive days. Silymarin (100 mg/kg) was administered as a reference drug. 0.5 mL/kg of CCl₄ was injected intraperitoneally to induce acute liver injury. Body weight gain, relative liver weight, serum chemistry, histopathological analysis, and hepatic endogenous antioxidants capacities were observed. Results : All diverse combinations of MSH significantly reduced relative liver weight increase by CCl₄. In addition, MSH administrations significantly decreased the elevation of serum alanine aminotransferase and aspartate aminotransferase activities by CCl₄. Histopathological observation indicated that all MSH treatments significantly reduced the increase of degenerated hepatocytes, inflammatory cell infiltration, and histological activity index score by CCl₄. Moreover, all MSH administrations reduced the elevation of malondialdehyde contents, and ameliorated the reduction of hepatic glutathione contents, superoxide dismutase activity, and catalase activity. Among the various mixing ratio of MSH combinations, MSH 1:1 and 2:1 showed the most potent anti-oxidative stress, and hepatoprotective effect. Conclusion : Present results suggest that 1:1 and 2:1 combinations of MSH is promising herbal formulation with the hepatoprotective effect against oxidative stress.

• Journal of Korean Neurosurgical Society
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• v.66 no.5
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• pp.511-524
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• 2023

Objective : This animal model aimed to compare the rat group that received brain irradiation and did not receive additional treatment (only saline) and the rat group that underwent brain irradiation and received Granulocyte colony stimulating factor (G-CSF) treatment. In addition, the effects of G-CSF on brain functions were examined by magnetic resonance (MR) imaging and histopathologically. Methods : This study used 24 female Wistar albino rats. Drug administration (saline or G-CSF) was started at the beginning of the study and continued for 15 days after whole-brain radiotherapy (WBRT). WBRT was given on day 7 of the start of the study. At the end of 15 days, the behavioral tests, including the three-chamber sociability test, open field test, and passive avoidance learning test, were done. After the behavioral test, the animals performed the MR spectroscopy procedure. At the end of the study, cervical dislocation was applied to all animals. Results : G-CSF treatment positively affected the results of the three-chamber sociability test, open-space test and passive avoidance learning test, cornu Ammonis (CA) 1, CA3, and Purkinje neuron counts, and the brain levels of brain-derived neurotrophic factor and postsynaptic density protein-95. However, G-CSF treatment reduced the glial fibrillary acidic protein immunostaining index and brain levels of malondialdehyde, tumor necrosis factor-alpha, nuclear factor kappa-B, and lactate. In addition, on MR spectroscopy, G-CSF had a reversible effect on brain lactate levels. Conclusion : In this first designed brain irradiation animal model, which evaluated G-CSF effects, we observed that G-CSF had reparative, neuroprotective and anti-neurodegenerative effects and had increased neurotrophic factor expression, neuronal counts, and morphology changes. In addition, G-CSF had a proven lactate-lowering effect in MR spectroscopy and brain materials.

• Animal Bioscience
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• v.36 no.4
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• pp.629-641
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• 2023

Objective: This study investigated the effects of extruded flaxseed with and without herbs mixture on egg performance, yolk fatty acids (FAs), lipid components, blood biochemistry, serological enzymes, antioxidants, and immune system of Hy-Line W-36 hens for nine weeks. Methods: Two hundred forty laying hens were randomly distributed to eight treatments, resulting in six replicates with five hens. Graded levels of dietary extruded flaxseed (0, 90, 180, and 270 g/kg) with and without herbs mixture (24 g/kg: garlic, ginger, green tea, and turmeric 6 g/kg each) were designed as treatments. Results: The two-way analysis of variance indicated that hens fed herbs mixture had a higher value of egg production, yolk high-density lipoprotein (HDL), superoxide dismutase, glutathione peroxidase, and white blood cell and lower contents of yolk cholesterol, glucose, and blood low-density lipoprotein than those fed diets without herb mixtures (p<0.05). The Flx27 (270 g/kg flaxseed) (153.5 g/kg n-3 FAs) and Flx27+H (270 g/kg flaxseed plus 24 g/kg herbs mixture) (150.5 g/kg n-3 FAs) groups were the most promising treatments in terms of yolk n-3 FAs content. In-teraction effect (herbs- flaxseed) for blood cholesterol, HDL, malondialdehyde, glutaredoxin, alanine transaminase, (ALT), aspartate transaminase (AST), haemoglobin and immune parameters was significant (p<0.05). The results showed layers fed herbs mixture (Flx9+H, Flx18+H, and Flx27+H) had a better value of total antibody, immunoglobulin M, immunoglobulin G, ALT, AST, and blood HDL as compared with representative flaxseed levels without herbs. Conclusion: High inclusion levels of extruded flaxseed (270 g/kg) without herbs to enrich eggs with n-3 appears to impair the antioxidant system, immunohematological parameters, and sero-logical enzymes. Interestingly, the herbs mixture supplementation corrected those effects. Therefore, feeding layers with flaxseed-rich diets (270 g/kg) and herbs mixture can be a promising strategy to enrich eggs with n-3 FAs.

• Animal Bioscience
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• v.36 no.8
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• pp.1241-1251
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• 2023

Objective: Egg yolk immunoglobulin (IgY) is an antibiotic alternative to prevent and fight intestinal pathogenic infections. This study aimed to investigate the effects of sodium alginate/chitosan/sodium alginate IgY microcapsules on the growth performance, serum parameters, and intestinal health of broiler chickens. Methods: One-day-old broilers (Ross 308) were divided into five treatments, each with 10 replicates of five chickens. The dietary treatments were maintained for 28 days and consisted of a basal diet (NC), basal diet + 500 mg chlortetracycline/kg diet (CH), basal diet + 50 mg non-microencapsulated IgY/kg diet (NM), basal diet + 600 mg low levels microencapsulated IgY/kg diet (LM), and basal diet + 700 mg high levels microencapsulated IgY/kg diet (HM). Results: Throughout the 28-day trial period, the NM, LM, HM, and CH groups increased average daily gain compared with the NC group (p<0.05), and the HM group reduced feed conversion ratio compared with the CH group (p<0.05). The LM and HM groups increased relative organ weights of thymus and spleen compared with the CH and NM groups (p<0.05). The HM group improved the duodenal, jejunal and ileum villi height (VH) and villus height to crypt depth ratio (VH:CD) compared with the CH and NM groups (p<0.05). Compared with the CH group, the HM group increased serum immunoglobulin (IgA), immunoglobulin G (IgG), superoxide dismutase, total antioxidant capacity, and glutathione peroxidase levels (p<0.05), and decreased serum malondialdehyde levels (p<0.05). Compared with the NC group, the NM, LM, HM, and CH groups reduced colonic Escherichia coli and Salmonella levels (p<0.05). and the HM group promoted the levels of lactic acid bacteria and bifidobacteria compared with the CH group (p<0.05). Conclusion: Microencapsulation could be considered as a way to improve the efficiency of IgY. The 700 mg high levels microencapsulated IgY/kg diet could potentially be used as an alternative to antibiotics to improve the immune performance and intestinal health, leading to better performance of broiler chickens.

• The Journal of Internal Korean Medicine
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• v.44 no.3
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• pp.402-417
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• 2023

Objective: Liver fibrosis is a highly conserved wound-healing response and the final common pathway of chronic inflammatory injury. This study aimed to evaluate the potential anti-fibrotic effect of the combination of Rhei Radix et Rhizoma water extract (RW) and silymarin in a thioacetamide (TAA)-induced liver fibrosis model. Methods: The liver fibrosis mouse model was established through the intraperitoneal injection of TAA (1 week 100 mg/kg, 2-3 weeks 200 mg/kg, 4-8 weeks 400 mg/kg) three times per week for eight weeks. Animal experiments were conducted in five groups; Normal, Control (TAA-induced liver fibrosis mice), Sily (silymarin 50 mg/kg), RSL (RW 50 mg/kg+silymarin 50 mg/kg), and RSH (RW 100 mg/kg+silymarin 50 mg/kg). Biochemical analyses were measured in serum, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), malondialdehyde (MDA), and ammonia levels. Liver inflammatory cytokines and fibrous biomarkers were measured by Western blot analysis, and liver histopathology was evaluated through tissue staining. Results: A significant decrease in the liver function markers AST and ALT and a reduction in ammonia and total bilirubin were observed in the group treated with RSL and RSH. Measurement of reactive oxygen species and MDA revealed a significant decrease in the RSL and RSH administration group compared to the TAA induction group. The expression of extracellular matrix-related proteins, such as transforming growth factor β1, α-smooth muscle actin, and collagen type I alpha 1, was likewise significantly decreased. All drug-administered groups had increased matrix metalloproteinase-9 but a decreasing tissue inhibitor of matrix metalloproteinase-1. RSL and RSH exerted a significant upregulation of NADPH oxidase 2, p22^phox, and p47^phox, which are oxidative stress-related factors. Furthermore, pro-inflammatory proteins such as cyclooxygenase 2 and interleukin-1β were markedly suppressed through the inhibition of nuclear factor kappa B activation. Conclusions: The administration of RW and silymarin suppressed the NADPH oxidase factor protein level and showed a tendency to reduce inflammation-related enzymes. These results suggest that the combined administration of RW and silymarin improves acute liver injury induced by TAA.

• Nutrition Research and Practice
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• v.17 no.4
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• pp.670-681
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• 2023

BACKGROUND/OBJECTIVES: Oxidative stress is caused by reactive oxygen species and free radicals that accelerate inflammatory responses and exacerbate fatigue. Tormentic acid (TA) has antioxidant and anti-inflammatory properties. Thus, the aim of present study is to determine the fatigue-regulatory effects of TA in H₂O₂-stimulated myoblast cell line, C2C12 cells and treadmill stress test (TST) and forced swimming test (FST) animal models. MATERIALS/METHODS: In the in vitro study, C2C12 cells were pretreated with TA before stimulation with H₂O₂. Then, malondialdehyde (MDA), lactate dehydrogenase (LDH), creatine kinase (CK) activity, tumor necrosis factor (TNF)-α, interleukin (IL)-6, superoxide dismutase (SOD), catalase (CAT), glycogen, and cell viability were analyzed. In the in vivo study, the ICR male mice were administered TA or distilled water orally daily for 28 days. FST and TST were then performed on the last day. In addition, biochemical analysis of the serum, muscle, and liver was performed. RESULTS: TA dose-dependently alleviated the levels of MDA, LDH, CK activity, TNF-α, and IL-6 in H₂O₂-stimulated C2C12 cells without affecting the cytotoxicity. TA increased the SOD and CAT activities and the glycogen levels in H₂O₂-stimulated C2C12 cells. In TST and FST animal models, TA decreased the FST immobility time significantly while increasing the TST exhaustion time without weight fluctuations. The in vivo studies showed that the levels of SOD, CAT, citrate synthase, glycogen, and free fatty acid were increased by TA administration, whereas TA significantly reduced the levels of glucose, MDA, LDH, lactate, CK, inflammatory cytokines, alanine transaminase, aspartate transaminase, blood urea nitrogen, and cortisol compared to the control group. CONCLUSIONS: TA improves fatigue by modulating oxidative stress and energy metabolism in C2C12 cells and animal models. Therefore, we suggest that TA can be a powerful substance in healthy functional foods and therapeutics to improve fatigue.

• Animal Bioscience
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• v.35 no.9
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• pp.1434-1443
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• 2022

Objective: This study was designed to investigate the hypothesis that dietary quercetin (QUE) and coated sodium butyrate (SB) supplementation alleviate oxidative stress in the small intestine of diquat (DIQ)-challenged pullets. Methods: A total of 200 13-week-old pullets were divided into four groups: the control group (CON), the DIQ group, the QUE group, and the coated SB group, and injected intraperitoneally with either saline (CON) or diquat (DIQ, QUE, and SB) to induce oxidative stress on day 0. Results: On the first day, the malondialdehyde and superoxide dismutase (SOD) concentrations in the SB group were significantly different from those in the DIQ and QUE groups (p<0.05), and dietary supplementation with SB increased serum glutathione peroxidase (GSH-PX) levels compared with the DIQ group (p<0.05). Quercetin and SB increased the levels of CLAUDIN-1 and zonula occludens-1 (ZO-1) in the jejunum. On the tenth day of treatment, QUE attenuated the decrease in GSH-PX levels compared to those of the CON group (p<0.05), while SB increased SOD, GSH-PX, and total antioxidant capacity levels compared to those of the DIQ group. Nuclear factor erythroid 2-related factor 2 (NRF2) and heme oxygenase-1 (HO-1) mRNA levels in the QUE and SB groups increased (p<0.05) and CLAUDIN-1 mRNA levels in the QUE and SB groups were upregulated compared to those in the DIQ group ileum tissue. Conclusion: Supplementation of QUE and SB demonstrated the ability to relieve oxidative stress in pullets post DIQ-injection with a time-dependent manner and QUE and SB may be potential antioxidant additives for relieving oxidative stress and protecting the intestinal barrier of pullets.

• Animal Bioscience
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• v.37 no.6
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• pp.1001-1006
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• 2024

Objective: This study aimed to investigate the effect of Codonopsis pilosula polysaccharide (CPP) on the motility, mitochondrial integrity, acrosome integrity rate, and antioxidant ability of sheep sperm after preservation at 4℃. Methods: Semen from healthy adult rams were collected and divided into four groups with separate addition of 0, 200, 400, and 1,000 mg/L CPP. Sperm motility was analyzed using the Computer-Assisted Semen Analysis software after preservation at 4℃ for 24, 72, 120, and 168 h. Sperm acrosome integrity rate was analyzed by Giemsa staining at 24, 72, and 120 h, and mitochondrial membrane integrity was analyzed by Mito-Tracker Red CMXRos. The total antioxidant capacity (T-AOC) and malondialdehyde (MDA) content of spermatozoa were measured after 120 h of preservation. Results: The sperm viability and forward-moving sperm under 200 mg/L CPP were significantly higher than that in the control group at 72 h (61.28%±3.89% vs 52.83%±0.70%, 51.53%±4.06% vs 42.84%±1.14%), and 168 h (47.21%±0.85% vs 41.43%±0.37%, 38.68%±0.87% vs 31.68%±0.89%). The percentage of fast-moving sperm (15.03%±1.10% vs 11.39%±1.03%) and slow-moving sperm (23.63%±0.76% vs 20.29%±1.11%) in the 200 mg/L group was significantly higher than control group at 168 h. The mitochondrial membrane integrity of the sperm in the group with 200 mg/L CPP was significantly higher than those in the control group after storage at 4℃ for 120 h (74.76%±2.54% vs 65.67%±4.51%, p<0.05). The acrosome integrity rate in the group with 200 mg/L (87.66%±1.26%) and 400 mg/L (84.00%±2.95%) was significantly higher than those in the control group (80.65%±0.16%) after storage for 24 h (p<0.05). CPP also increased T-AOC and decreased the MDA concentration after preservation at 4℃ (p<0.05). Conclusion: Adding CPP could improve the T-AOC of sperm, inhibit lipid peroxidation, and facilitate semen preservation.