• Title/Summary/Keyword: Keap1-Nrf2 pathway

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Effect of Paeoniae Radix Alba on a thioacetamide induced liver fibrosis mice model (Thioacetamide로 유발된 간섬유증 동물 모델에서 백작약이 미치는 효능)

  • Lee, Se Hui;Lee, Jin A;Shin, Mi-Rae;Seo, Bu-Il;Roh, Seong-Soo
    • Korean Journal of Food Science and Technology
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    • v.53 no.5
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    • pp.544-552
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    • 2021
  • This study investigated the anti-fibrotic and antioxidant effects of Paeonia Radix Alba water extract (PR) on thioacetamide (TAA)-induced liver fibrosis in a mouse model and its underlying mechanisms. Liver fibrosis was induced by intraperitoneal injection of TAA (three times a week) for 8 weeks. Furthermore, silymarin (50 mg/kg body weight) and PR (200 mg/kg body weight) were administered for 8 weeks. PR treatment downregulated aspartate aminotransferase (AST), alanine aminotransferase (ALT), ammonia, and myeloperoxidase levels. Moreover, PR treatment downregulated NOX2 and p47phox and upregulated antioxidant enzymes by activating the Nrf2/Keap1 signaling pathway. Furthermore, PR inhibited the factors associated with fibrosis, such as α-SMA and collagen I. AMPK/SIRT1 was upregulated by PR treatment. Overall, these results suggest that PR attenuates liver fibrosis by regulating the Nrf2/Keap1 and AMPK/SIRT1/NF-κB signaling pathways through the inhibition of oxidative stress. Hence, PR has potential as a remedy for preventing and treating liver fibrosis.

Antioxidant mechanism of black garlic extract involving nuclear factor erythroid 2-like factor 2 pathway

  • Ha, Ae Wha;Kim, Woo Kyoung
    • Nutrition Research and Practice
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    • v.11 no.3
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    • pp.206-213
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    • 2017
  • BACKGROUN/OBJECTIVES: Although studies have revealed that black garlic is a potent antioxidant, its antioxidant mechanism remains unclear. The objective of this study was to determine black garlic's antioxidant activities and possible antioxidant mechanisms related to nuclear factor erythroid 2-like factor 2 (Nrf2)-Keap1 complex. METHODS/MATERIALS: After four weeks of feeding rats with a normal fat diet (NF), a high-fat diet (HF), a high-fat diet with 0.5% black garlic extract (HF+BGE 0.5), a high-fat diet with 1.0% black garlic extract (HF+BGE 1.0), or a high-fat diet with 1.5% black garlic extract (HF+BGE 1.5), plasma concentrations of glucose, insulin,homeostatic model assessment of insulin resistance (HOMA-IR) were determined. As oxidative stress indices, plasma concentrations of thiobarbituric acid reactive substances (TBARS) and 8-isoprostaglandin $F2{\alpha}$ (8-iso-PGF) were determined. To measure antioxidant capacities, plasma total antioxidant capacity (TAC) and activities of antioxidant enzymes in plasma and liver were determined. The mRNA expression levels of antioxidant related proteins such as Nrf2, NAD(P)H: quinone-oxidoreductase-1 (NQO1), heme oxygenase-1 (HO-1), glutathione reductase (GR), and glutathione S-transferase alpha 2 (GSTA2) were examined. RESULTS: Plasma glucose level, plasma insulin level, and HOMA-IR in black garlic supplemented groups were significantly (P < 0.05) lower than those in the HF group without dose-dependent effect. Plasma TBARS concentration and TAC in the HF+BGE 1.5 group were significantly decreased compared to those of the HF group. The activities of catalase and glutathione peroxidase were significantly (P < 0.05) increased in the HF+BGE 1.0 and HF+BGE 1.5 groups compared to those of the HF group. The mRNA expression levels of hepatic Nrf2, NQO1, HO-1, and GSTA2 were significantly (P < 0.05) increased in the HF with BGE groups compared to those in the HF group. CONCLUSIONS: The improvements of blood glucose homeostasis and antioxidant systems in rats fed with black garlic extract were related to mRNA expression levels of Nrf2 related genes.

The Protective Effect of Arecae Semen and Coptidis Rhizoma in a Chronic Reflux Esophagitis Rat Model (만성 역류성 식도염 모델에서 빈랑(檳榔)와 황련(黃連) 복합물의 보호 효과)

  • Lee, Se Hui;Lee, Jin A;Shin, Mi-Rae;Lee, Ji Hye;Roh, Seong-Soo
    • The Journal of Internal Korean Medicine
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    • v.42 no.1
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    • pp.11-24
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    • 2021
  • Objective: Chronic reflux esophagitis (CRE), characterized by esophageal mucosa ulcer, is caused by continuous backflow of gastric acid and consequent inflammation due to unstable gastroesophageal sphincter. The aim of the present study was to clarify the effect of an Arecae Semen and Coptidis Rhizoma mixture (AC-mix) on CRE. Methods: CRE was surgically induced in SD rats with three experimental groups used: normal; CRE control; and CRE treatment (200 mg/kg AC-mix). Blood and esophageal tissue were collected after two weeks of drug administration. The anti-oxidant activity of the AC-mix was measured by total polyphenol and total flavonoid contents as well as by radical scavenging activity with protein levels evaluated using western blotting. Results: CRE damage to the esophageal mucosa was significantly reduced in the AC-mix group as compared with the controls, and administration of the AC-mix was seen to inhibit NF-κBp65 activity. Consequently, the inactivation of NF-κBp65 significantly inhibited inflammatory mediators such as COX-2 and iNOS. Moreover, the anti-oxidant enzyme HO-1 significantly increased through activation of the Nrf2-Keap1 pathway. Matrix metalloproteinase-2 (MMP-2), which can break down collagen from the basement membrane and extracellular matrix, was decreased following AC-mix treatment, and elevated levels of MMP-2 were regulated by its tissue inhibitor. Conclusions: These results show that AC-mix can alleviate esophageal mucosa ulcer though inhibition of the NF-κBp65 inflammatory pathway and enhancement of the anti-oxidant Nrf2-Keap1 pathway.

The Beneficial Effects of Ferulic Acid supplementation during In Vitro Maturation of Porcine Oocytes on Their Parthenogenetic Development

  • Lee, Kyung-Mi;Hyun, Sang-Hwan
    • Journal of Embryo Transfer
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    • v.32 no.4
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    • pp.257-265
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    • 2017
  • Ferulic Acid (FA) is a metabolite of phenylalanine and tyrosine, a phenolic compound commonly found in fruits and vegetables. Several studies have shown that FA has various functions such as antioxidant effect, prevention of cell damage from irradiation, protection from cell damage caused by oxygen deficiency, anti-inflammatory action, anti-aging action, liver protective effect and anti-cancer action. In this study, we investigated the maturation rate, intracellular glutathione (GSH) and reactive oxygen species (ROS) of porcine oocytes by adding FA to the in vitro maturation (IVM) medium and examined subsequent embryonic developmental competence at 5% oxygen through parthenogenesis. There is no significant difference between the control group ($0{\mu}M$) and treatment groups ($5{\mu}M$, $10{\mu}M$, $20{\mu}M$) on maturation rates. Intracellular GSH levels in oocyte treated with $5{\mu}M$ of FA significantly increased (P < 0.05), and $20{\mu}M$ of FA revealed significant decrease (P < 0.05) in intracellular ROS levels compared with the control group. Oocytes treated with FA exhibited significantly higher cleavage rates (79.01% vs 89.19%, 92.20%, 90.89%, respectively) than the control group. Oocytes treated with $10{\mu}M$ showed significantly higher blastocyst formation rates (28.3% vs 40.3%, respectively) after PA than the control group. Total cell numbers in blastocyst of $10{\mu}M$ FA displayed significantly higher (39.4 vs 51.9, respectively) than the control group. In conclusion, these results suggested that treatment with FA during IVM improved the developmental potential of porcine embryos by increasing intracellular GSH synthesis and reducing ROS levels. Also, there was an improvement of cleavage rate, blastocyst formation and total cell numbers in blastocysts. It might be associated with Keap1-Nrf2 pathway as an antioxidant regulate pathway that plays a crucial role in determining the sensitivity of cells to oxidative damages by regulating the basal and inducible expression of enzymes which is related to detoxification and anti-oxidative effects, stress response enzymes and/or proteins and ABC transporters.

Effect of Coptidis Rhizoma and Evodiae Fructus Mixture on Esophageal Mucosa in Chronic Reflux Esophagitis (만성 역류성 식도염에서 황련과 오수유 혼합물이 식도 점막에 미치는 효과)

  • Lee, Jin A;Shin, Mi-rae;Lee, Ji Hye;Roh, Seong-soo
    • Korean Journal of Pharmacognosy
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    • v.51 no.4
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    • pp.349-359
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    • 2020
  • Gastroesophageal reflux disease (GERD) is a disease that stomach contents continually refluxing, and is currently on the rise worldwide. The purpose of this study is to find natural materials that can reduce side effects and effectively treat chronic acid reflux esophagitis (CARE), one of GERD. First, the antioxidant activity was confirmed by varying the mixing ratio of Coptidis Rhizoma and Evodiae Fructus, which are effective against chronic reflux esophagitis. After, animal experiments were conducted using a 1:1 (CE) and 1:2 (CEE) combination ratio of Coptidis Rhizoma and Evodiae Fructus, which had the best antioxidant efficacy. Gross lesion of esophageal mucosa after CE or CEE treatment showed a superior enhancement compared with that of CARE control rats. Additionally, its inhibited MAPK phosphorylation and led NF-κB inactivation through the suppression of IκBα phosporylation by regulating Nrf2/Keap-1, and NF-κB inactivation induced reduced protein expressions including inflammatory mediators and cytokines. Moreover, its improved esophageal barrier function through upregulating protein expressions of tight junction protein, whereas downregulating protein expressions of MMPs. Taken together, a mixture of Coptidis Rhizoma and Evodiae Fructus can attenuate the esophageal mucosal ulcer by inhibiting MAPK and NF-κB pathway, and upregulating proteins associated with tight junction.

The anti-inflammatory influence of fermented soy products containing a fermented Rhus verniciflua extract on lipopolysaccharide (LPS)-treated RAW 264.7 cells (LPS 유도 RAW264.7세포에서 발효 옻 추출물을 함유한 장류의 항염증 효과)

  • Lim, Hyun Ji;Kim, Hyoun-Young;Lee, Jeong-Mi;Kim, Hyun Ju
    • Korean Journal of Food Science and Technology
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    • v.50 no.6
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    • pp.642-652
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    • 2018
  • Rhus verniciflua (RV) Stokes is a herbal medicine that helps improve blood circulation by stimulating digestion, removing extravasated blood, and raising body temperature. The purpose of this research was to study the anti-inflammatory effect of fermented soy products (FSP) containing a fermented RV (FRV) extract on lipopolysaccharides (LPS)-treatedd RAW 264.7 cells. Treatment with FRV extracts (1, 10, $100{\mu}g/mL$) downregulated nitric oxide (NO) and pro-inflammatory cytokines as compared to the LPS-treated group. Besides, the RV extract treatment suppressed the expression of genes related to pro-inflammatory cytokines, matrixins, inflammation, and apoptosis, while increasing the expression of genes involved in the antioxidant system. Furthermore, RVS extract upregulated antioxidant enzymes, such as glutathione, Cu,Zn-SOD, and catalase without changes in the Nrf2-Keap1 pathway. FSP (doenjang, ganjang) containing FRV extracts (0.1, 1, or $10{\mu}g/mL$) significantly decreased the NO and IL-6 levels in an FSP after 8 weeks of fermentation, but not the expression of genes involved in the inflammation and antioxidant system. These result indicate that an FRV extract and FSPs have a potential application in inflammatory conditions.