• Title/Summary/Keyword: Nuclear factor-erythroid-2 related factor 2 (Nrf2)/heme oxygenase-1 (HO-1)

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The Anti-Inflammatory Effect of Trichilia martiana C. DC. in the Lipopolysaccharide-Stimulated Inflammatory Response in Macrophages and Airway Epithelial Cells and in LPS-Challenged Mice

  • Park, Ji-Won;Ryu, Hyung Won;Ahn, Hye In;Min, Jae-Hong;Kim, Seong-Man;Kim, Min-Gu;Kwon, Ok-Kyoung;Hwang, Daseul;Kim, Soo-Yong;Choi, Sangho;Zamora, Nelson;Rosales, Kattia;Oh, Sei-Ryang;Lee, Jae-Won;Ahn, Kyung-Seop
    • Journal of Microbiology and Biotechnology
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    • v.30 no.11
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    • pp.1614-1625
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    • 2020
  • A number of species of the genus Trichilia (Meliaceae) exhibit anti-inflammatory effects. However, the effect of Trichilia martiana C. DC. (TM) on lipopolysaccharide (LPS)-induced inflammation has not, to the best of our knowledge, yet been determined. Therefore, in the present study, the antiinflammatory effect of TM on LPS-stimulated RAW264.7 macrophages was evaluated. The ethanol extract of TM (TMEE) significantly inhibited LPS-induced nitric oxide (NO), prostaglandin 2 (PGE2), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). TMEE also reduced the levels of inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β and IL-6. The upregulation of mitogen-activated protein kinases (MAPKs) and NF-κB activation was revealed to be downregulated following TMEE pretreatment. Furthermore, TMEE was indicated to lead to the nucleus translocation of nuclear factor erythroid-derived 2-related factor 2 (Nrf2) and the expression of heme oxygenase-1 (HO-1). In H292 airway epithelial cells, the pretreatment of TMEE significantly downregulated the production of LPS-stimulated IL-1β, and TMEE was indicated to increase the expression of HO-1. In animal models exhibiting LPS-induced acute lung injury (ALI), treatment with TMEE reduced the levels of macrophages influx and TNF-α production in the bronchoalveolar lavage fluid (BALF) of ALI mice. Additionally, TMEE significantly downregulated the activation of ERK, JNK and IκB, and upregulated the expression of HO-1 in the lungs of ALI mice. In conclusion, the results of the current study demonstrated that TMEE could exert a regulatory role in the prevention or treatment of the endotoxin-mediated inflammatory response.

Panax ginseng and its ginsenosides: potential candidates for the prevention and treatment of chemotherapy-induced side effects

  • Wan, Yan;Wang, Jing;Xu, Jin-feng;Tang, Fei;Chen, Lu;Tan, Yu-zhu;Rao, Chao-long;Ao, Hui;Peng, Cheng
    • Journal of Ginseng Research
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    • v.45 no.6
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    • pp.617-630
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    • 2021
  • Chemotherapy-induced side effects affect the quality of life and efficacy of treatment of cancer patients. Current approaches for treating the side effects of chemotherapy are poorly effective and may cause numerous harmful side effects. Therefore, developing new and effective drugs derived from natural nontoxic compounds for the treatment of chemotherapy-induced side effects is necessary. Experiments in vivo and in vitro indicate that Panax ginseng (PG) and its ginsenosides are undoubtedly non-toxic and effective options for the treatment of chemotherapy-induced side effects, such as nephrotoxicity, hepatotoxicity, cardiotoxicity, immunotoxicity, and hematopoietic inhibition. The mechanism focus on anti-oxidation, anti-inflammation, and anti-apoptosis, as well as the modulation of signaling pathways, such as nuclear factor erythroid-2 related factor 2 (Nrf2)/heme oxygenase-1 (HO-1), P62/keap1/Nrf2, c-jun Nterminal kinase (JNK)/P53/caspase 3, mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinases (ERK), AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR), mitogen-activated protein kinase kinase 4 (MKK4)/JNK, and phosphatidylinositol 3-kinase (PI3K)/AKT. Since a systemic review of the effect and mechanism of PG and its ginsenosides on chemotherapy-induced side effects has not yet been published, we provide a comprehensive summarization with this aim and shed light on the future research of PG.

Antioxidant and hepatoprotective effects of Korean ginseng extract GS-KG9 in a D-galactosamine-induced liver damage animal model

  • Jo, Yun Ho;Lee, Hwan;Oh, Myeong Hwan;Lee, Gyeong Hee;Lee, You Jin;Lee, Ji Sun;Kim, Min Jung;Kim, Won Yong;Kim, Jin Seong;Yoo, Dae Seok;Cho, Sang Won;Cha, Seon Woo;Pyo, Mi Kyung
    • Nutrition Research and Practice
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    • v.14 no.4
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    • pp.334-351
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    • 2020
  • BACKGROUND/OBJECTIVES: This study was designed to investigate the improvement effect of white ginseng extract (GS-KG9) on D-galactosamine (Ga1N)-induced oxidative stress and liver injury. SUBJECTS/METHODS: Sixty Sprague-Dawley rats were divided into 6 groups. Rats were orally administrated with GS-KG9 (300, 500, or 700 mg/kg) or silymarin (25 mg/kg) for 2 weeks. The rats of the GS-KG9- and silymarin-treated groups and a control group were then intraperitoneally injected Ga1N at a concentration of 650 mg/kg for 4 days. To investigate the protective effect of GS-KG9 against GalN-induced liver injury, blood liver function indicators, anti-oxidative stress indicators, and histopathological features were analyzed. RESULTS: Serum biochemical analysis indicated that GS-KG9 ameliorated the elevation of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) in GalN-treated rats. The hepatoprotective effects of GS-KG9 involved enhancing components of the hepatic antioxidant defense system, including glutathione, glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT). In addition, GS-KG9 treatment inhibited reactive oxygen species (ROS) production induced by GalN treatment in hepatocytes and significantly increased the expression levels of nuclear factor erythroid-2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) proteins, which are antioxidant proteins. In particular, by histological analyses bases on hematoxylin and eosin, Masson's trichrome, α-smooth muscle actin, and transforming growth factor-β1 staining, we determined that the administration of 500 mg/kg GS-KG9 inhibited hepatic inflammation and fibrosis due to the excessive accumulation of collagen. CONCLUSIONS: These findings demonstrate that GS-KG9 improves GalN-induced liver inflammation, necrosis, and fibrosis by attenuating oxidative stress. Therefore, GS-KG9 may be considered a useful candidate in the development of a natural preventive agent against liver injury.

Effects of hot water extracts of roasted radish against renal oxidative stress induced by high-fat diet (고지방식사로 유도된 신장 산화스트레스를 개선하는 가압볶음 무말랭이 열수추출물 효과)

  • Jeon, Yeonhui;Kim, Mijeong;Han, Seongkyung;Song, Yeong-Bok;Song, Yeong Ok
    • Korean Journal of Food Science and Technology
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    • v.49 no.2
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    • pp.203-208
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    • 2017
  • The antioxidant and anti-inflammatory effects of roasted dried radish (RDR) against renal oxidative stress were examined in high-fat diet (HFD)-fed mice. The HFD was prepared by adding lard to chow diet to provide 50% of the calories from fat. Hot water extracts of dried radish (DR) or RDR were administered orally to mice at 237 mg/kg bw/day, whereas distilled water was administered as a vehicle for 12 weeks. Compared to the control group, renal reactive oxygen species, peroxynitrite, and thiobarbituric acid reactive substance level in the DR or RDR group were significantly decreased, whereas the glutathione level was increased (p<0.05). Protein expressions of antioxidant factors such as nuclear factor erythroid 2-related factor-2, heme oxygenase-1, glutathione S-transferase, superoxide dismutase, catalase, and glutathione peroxidase were significantly increased in the DR and RDR groups; however, nuclear factor-kappa B expression was suppressed (p<0.05). These antioxidant and anti-inflammatory effects of RDR were found to be significantly greater than those of DR.

Effects of fermented soybean meal with Bacillus velezensis, Lactobacillus spp. or their combination on broiler performance, gut antioxidant activity and microflora

  • Tsai, C.F.;Lin, L.J.;Wang, C.H.;Tsai, C.S.;Chang, S.C.;Lee, T.T.
    • Animal Bioscience
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    • v.35 no.12
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    • pp.1892-1903
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    • 2022
  • Objective: A series of experiment were conducted to evaluate the effects of replacing a part of soybean meal (SBM) at 6% of broiler diets with fermented soybean meal (FSBM) obtained by single or two-stage fermentation by measuring growth performance, antioxidant activity in the jejunum and distal intestinal microflora. Methods: Soybean meal samples were prepared by single-stage fermentation using Bacillus velezensis (Bv) (FSBMB), or Lactobacillus spp. (as commercial control) (FSBML). Additional SBM sample was prepared by two-stage fermentation using Bv and subsequently using Lactobacillus brevis ATCC 367 (Lb) (FSBMB+L). Enzyme activity, chemical composition, trichloroethanoic acid-nitrogen solubility index (TCA-NSI) and antioxidant activity were measured. Then, in an in vivo study, 320 Ross308 broilers were divided into four groups with ad libitum supply of feed and water. Four groups were fed either a corn-soybean meal diet (SBM), or one of fermented SBM diets (FSBMB+L, FSBMB, and FSBML). Growth, serum characteristics, microflora, and the mRNA expression of selected genes were measured. Results: Compared to SBM, FSBMB+L contained lower galacto-oligosaccharide, allergic protein, and trypsin inhibitor, and higher TCA-NSI by about three times (p<0.05). Reducing power and 1,1-diphenyl-2-picrylhydrazyl free radical scavenging ability correlated positively with the TCA-NSI content in FSBM. Growth performances were not significantly different among four groups. In jejunum of 35-day-old broilers, partial replacement of SBM by FSBMB+L increased the activity of superoxide dismutase and catalase (CAT), and the FSBMB group had the highest catalase activity (p<0.05). Partial replacement of SBM by FSBM increased relative mRNA expressions of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and peptide transporter 1 (PepT1) (p<0.05); however, FSBMB+L increased CAT mRNA level to 5 times of the control (p<0.05). Conclusion: Using Bv- and Lb-processed SBM through two-stage fermentation to partially replace 6% of diets will improve the gut's antioxidant activity under commercial breeding in broilers.

Effects of quercetin and coated sodium butyrate dietary supplementation in diquat-challenged pullets

  • Zhou, Ning;Tian, Yong;Liu, Wenchao;Tu, Bingjiang;Gu, Tiantian;Xu, Wenwu;Zou, Kang;Lu, Lizhi
    • 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.

Ethanol Extract of Glycyrrhiza uralensis Protects Against Oxidative Stress-induced DNA Damage and Apoptosis in Retinal Pigment Epithelial Cells (망막색소상피세포에서 감초 추출물의 산화적 스트레스에 의한 DNA 손상 및 apoptosis 유발의 차단 효과)

  • Kim, So Young;Kim, Jeong-Hwan;Kim, Sung Ok;Park, Seh-Kwang;Jeong, Ji-Won;Kim, Mi-Young;Lee, Hyesook;Cheong, JaeHun;Choi, Yung Hyun
    • Journal of Life Science
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    • v.29 no.11
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    • pp.1273-1280
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    • 2019
  • Age-related macular degeneration (AMD) is one of the leading causes of blindness in the elderly population, and damage to retinal pigment epithelial (RPE) cells due to oxidative stress contributes to the development of AMD. Glycyrrhiza uralensis Fischer is one of the most widely used herbal medicines for the treatment of various diseases in Asian countries. Although recent studies indicated that treatment with G. uralensis can protect cells from oxidative stress, its mechanisms in RPE cells remain unknown. We evaluated the effect of a G. uralensis ethanol extract (GU) on $H_2O_2$-induced oxidative injury in ARPE-19 RPE cells. The GU pretreatment attenuated reactive oxygen species (ROS) generation induced by $H_2O_2$, which was associated with induced expression of nuclear factor erythroid-derived-2-like 2 (Nrf2) and heme oxygenase-1 (HO-1). GU also suppressed $H_2O_2$-induced DNA damage and mitochondrial dysfunction. The inhibitory effect of GU on $H_2O_2$-induced apoptosis was associated with the protection of caspase-3 activation. Overall, GU appeared to protect RPE cells from oxidative injury by inhibiting DNA damage and reducing apoptosis. Further studies are needed to determine the regulation of Nrf2-mediated HO-1 expression, but our results suggest the possibility of using GU to reduce the risk of AMD.