• Title/Summary/Keyword: AAPH

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A Newly Synthesized Flavone from Luteolin Escapes from COMT-Catalyzed Methylation and Inhibits Lipopolysaccharide-Induced Inflammation in RAW264.7 Macrophages via JNK, p38 and NF-κB Signaling Pathways

  • Ye, Lin;Xin, Yang;Wu, Zhi-yuan;Sun, Hai-jian;Huang, De-jian;Sun, Zhi-qin
    • Journal of Microbiology and Biotechnology
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    • v.32 no.1
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    • pp.15-26
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    • 2022
  • Luteolin is a common dietary flavone possessing potent anti-inflammatory activities. However, when administrated in vivo, luteolin becomes methylated by catechol-O-methyltransferases (COMT) owing to the catechol ring in the chemical structure, which largely diminishes its anti-inflammatory effect. In this study, we made a modification on luteolin, named LUA, which was generated by the chemical reaction between luteolin and 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH). Without a catechol ring in the chemical structure, this new flavone could escape from the COMT-catalyzed methylation, thus affording the potential to exert its functions in the original form when administrated in the organism. Moreover, an LPS-stimulated RAW cell model was applied to detect the anti-inflammatory properties. LUA showed much more superior inhibitory effect on LPS-induced production of NO than diosmetin (a major methylated form of luteolin) and significantly suppressed upregulation of iNOS and COX-2 in macrophages. LUA treatment dramatically reduced LPS-stimulated reactive oxygen species (ROS) and mRNA levels of pro-inflammatory mediators such as IL-1β, IL-6, IL-8 and IFN-β. Furthermore, LUA significantly reduced the phosphorylation of JNK and p38 without affecting that of ERK. LUA also inhibited the activation of NF-κB through suppression of p65 phosphorylation and nuclear translocation.

Antioxidant and Antihemolytic Activities of Ethanol Extracts of Carpesii Fructus and Farfarae Flos (학슬 및 관동화 에탄올 추출물의 항산화 및 항용혈 효과)

  • Kang, Hyun Ju;Kim, Hong-Jun;Jeong, Seung-Il;Kim, Hyeon Soo;Jeon, In Hwa;Mok, Ji Ye;Shim, Jae-Suk;Jang, Seon Il
    • The Korea Journal of Herbology
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    • v.28 no.3
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    • pp.25-31
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    • 2013
  • Objectives : To develop a natural antioxidant and anti-hemolytic agents, we investigated the effects of ethanol extracts of Carpesii Fructus and Farfarae Flos. Methods : Aerial parts of Carpesii Fructus and Farfarae Flos were extracted with 80% ethanol. Antioxidant activity of Carpesii Fructus or Farfarae Flos extract was evaluated by employing three different assays, i.e., 1,1-diphenyl-2-picryl hydrazyl (DPPH), 2,2'-azino-bis (3-ethylbenzthiazoline-6-suphonic acid) diammonium (ABTS) scavenging and reducing power activities. Also, anti-hemolytic activity of Carpesii Fructus or Farfarae Flos extract was determined using [2,2'-azobis (2-methylpropionamidine) dihydrochloride (AAPH)]-induced hemolysis, glutathione (GSH) depletion and malondialdehyde (MDA) formation in normal rat red blood cells (RBC) or plasma. Results : The extracts obtained from Carpesii Fructus and Farfarae Flos dose-dependently increased the scavenging activity on DPPH- or ABTS-induced radicals and the reducing power activities. Carpesii Fructus and Farfarae Flos were similar to the scavenging activity and the reducing power of butylated hydroxy anisole effect at high concentration ($1,000{\mu}g/mL$). RBC oxidative hemolysis and plasma MDA formation induced by AAPH were significantly suppressed by the extracts of Carpesii Fructus and Farfarae Flos in a dose-dependent manner. Also, Carpesii Fructus and Farfarae Flos extracts prevented the depletion of cystosolic antioxidant GSH in RBCs. Carpesii Fructus generally had better than the free radical scavenging activity, the reducing power and anti-hemolytic effects of Farfarae Flos. Conclusions : These results suggest that Carpesii Fructus and Farfarae Flos may have value as the potential antioxidant and anti-hemolytic medicinal plant.

Study on the Anti-oxidative Effects of Adenophorae Radix, Codonopsis lanceolatae Radix and Glehniae Radix Cum Rhizoma on Liver Cells Isolated from Oxidatively Stressed Rat (산화동물 모델 흰쥐 간세포에 대한 사삼(沙參), 양유근(羊乳根) 및 해방풍(海防風)의 항산화 효과 연구)

  • Min, Sang-Hong;Han, Hyo-Sang;Lee, Young-Jong
    • The Korea Journal of Herbology
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    • v.24 no.3
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    • pp.109-119
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    • 2009
  • Objectives : The present study was purposed to compare Adenophorae Radix (henceforth AR), Codonopsis lanceolatae Radix (henceforth ClR) and Glehniae Radix cum Rhizoma (henceforth GRcR) concerning their anti-oxidant effect. Methods : We measured eythrocyte, leukocyte, thrombocyte, serum albumin, total bilirubin, LDL cholesterol, and glucose as well as SOD, GSH, catalase, NO, and MDA in the rat liver oxidatively stressed by AAPH. Results : 1. The oxidative stress-induced thrombocyte levels were significantly decreased in CIR-treated and GRcR-treated groups. 2. The oxidative stress-impaired SOD acitivities were significantly recovered in AR-treated and GRcR-treated groups. 3. The oxidative stress-reduced GSH contents were significantly increased in ClR-treated and GRcR-treated groups. 4. The oxidative stress-reduced catalase contents were significantly increased in all of the three groups. 5. The oxidative stress-induced NO productions were significantly decreased in all of the three groups. Conclusions : AR, ClR, and GRcR altogether showed the anti-oxidant effect in the rat liver oxidatively stressed by AAPH. The anti-oxidant properties of tAR, ClR, and GRcR seem to be similar even if those have different botanical properties and different medical efficacies in oriental medicine.

A Study on Antioxidative Effects of Sipyimiguanjungtang and Osuyubujayijungtang, Korean Traditional Prescriptions for Soum Constitutes, in Brain and Liver of Rat (소음인(少陰人) 십이미관중탕(十二味寬中湯), 오수유부자이중탕(吳茱萸附子理中湯)이 흰쥐의 뇌(腦)와 간조직(肝組織)의 항산화(抗酸化) 기전(機轉)에 미치는 영향(影響))

  • Jung, Bong-yeon;Song, Il-byung
    • Journal of Sasang Constitutional Medicine
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    • v.11 no.2
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    • pp.227-250
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    • 1999
  • The free radical theory of aging was introduced in 1956 by Denham Harman. This aging theory proposed that normal aging results from random deleterious damage to tissues by free radical and supplying antioxidant lead to decrease oxidative damage, inhibit aging process. In this study, we investigated antioxidantive effects of four Korean constitutional prescriptions for 'Soum' constitution - Palmulgunjatang(Y1), Sipyimiguanjungtang(Y2), Osuyubujayijungtang(Y3) and Seungyangyikkibujatang(Y4). Antioxidative activity of this prescriptions was examined by 1,1-diphenyl-2-picrylhyrdazyl radicals, superoxide anion radicals, peroxyl radical, hydroxyl radical scavenging effects and erythrocyte hemolysis inhibitory effects. Y2 and Y3 were shown to have relatively high antioxidative activity on this methods. In additions, result of the cytoprotective effects of Korean constitutional prescriptions agianst 2,2'-azobis(amidinopropane) dihydrochloride (AAPH), a free radical initiator, induced cytotoxcity in human hepatoblastoma cell line was similarly obtained. On the basis of this result, we assayed the antioxidative effects of Y2 and Y3 on experimental oxidative damage, induced in mouse by 100mg/kg AAPH. Male ICR mouse were given oral administration of 500mg/kg Y2 and Y3 for 4 weeks. Thiobarbuturic acid reactive substance (TBARS) and protein degradation level in liver, plasma and brain as index of oxidative damage were decreased and thiol compound, total antioxidant status in plasma were increased by Y2 administration. But, Y3 injected group was decreased only protein degradation level in brain. Also, glutathione, a potent water-soluble endogenous antioxidant, concentration was increased by Y2 and Y3 administration in liver and brain. However, superoxide dismutase and catalase activity as a major antioxidative enzyme in vivo were not shown change by Y2 and Y3 administration. On the basis of these result, Y2 have an antioxidative effects on both water-soluble fraction and lipid-solube fraction in cell and tissues. But, Y3 has a lower antioxidative effects on lipid-soluble fraction than Y2 in cell and tissues. These results suggest that Y2 has a antioxidative effects by protect the tissue against oxygen free radical mediated oxidative damage and Y3 has a limited antioxidaitve effects on water-soluble fraction in vivo. Therefore, we make report that Y2 is more effective prescriptions for anti-aging or therapeutics of diseases.

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Antioxidative Activity on Human Low Density Lipoprotein(LDL) Oxidation by Pentagalloic Acid

  • Ryu, Beung-Ho;Kim, Hee-Sook;Moon, Yoon-Hee;Yang, Seong-Taek
    • Biotechnology and Bioprocess Engineering:BBE
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    • v.5 no.5
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    • pp.366-371
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    • 2000
  • The aim of this study was to investigate the efficiency of the pentagalloic acid compound in inhibiting the metal ions and cell lines that mediate in low density lipoprotein (LDL) oxidation. Pentagalloic acid prolonged the lag time preceeding the onset of conjugated diene formation. In chemically induced LDL oxidation by Cu$^2$(sup)+ plus hydrogen peroxide or peroxyl radical generated by 2, 2-azo-vis (2-amidino propane) hydrochloride (AAPH), pentagalloic acid inhibited LDL oxidation as monitored by measuring the thiobarbituric acid reactive substances(TBARS), malondialdehyde(MDA), and gel electrophoretic mobility. The physiological relevance of the antioxidative activity was validated at the cellular level where pentagalloic acid inhibited mouse macrophage J774 and endothelial cell-mediated LDL oxidation. When compared with several other antioxidants, pentagalloic acid showed a much higher ability than naturally occuring antioxidants, ${\alpha}$-tocopherol and ascorbic acid, and the synthetic antioxidant, probucol.

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Experimental study on antioxidant action of Kyungoktang (경옥탕(瓊玉湯)의 항산화작용(抗酸化作用)에 대한 실험적(實驗的) 연구(硏究))

  • Kim, Byung-Tak;Kim, Sung-Hoon
    • Journal of Haehwa Medicine
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    • v.7 no.1
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    • pp.741-748
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    • 1998
  • In order to evaluate the effectiveness of KOK(kyungokko) experimentally used for longevity hematology, erythrocyte hemolysis and TBA(thiobarbituric acid) were measured, after LKOK(low concentration KOK) and HKOK(high concentration KOK) were administrated to mice pretreated with AAPH (2,2'-Azobis(2-amidinopropane), hydrocholoride, free radical inducer. In hematology WBC and hemoglobin were reduced significantly, while the number of platelet was significantly incresed as compared with control. Erythrocyte hemolysis by damage of free radical on cell membrane of RBC and TBA(Thiobarbituric acid) were significantly inhibited in both sample groups as compared with control. These results suggest KOK had antioxidant effect.

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Antioxidant and Antigenotoxic Effects of Shiitake Mushrooms Affected by Different Drying Methods (건조 방법에 따른 표고버섯의 항산화능과 항유전독성 효과)

  • Kim, Min-Jung;Chu, Won-Mi;Park, Eun-Ju
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.41 no.8
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    • pp.1041-1048
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    • 2012
  • Shiitake mushroom (SM; Lentinus edodes) are cultivated and consumed in many Asian countries including Vietnam, China, Japan, Korea, and Thailand. In Asia, SM are mainly dried and used as flavoring. The aim of this study was to compare the effects of SM created with different drying processes, such as oven-dried and sun-dried, on the antioxidative and antigenotoxic effects. Raw and dried SM were extracted with acetone, ethanol, methanol, and hot water. The antioxidant effects of SM were evaluated by determining total phenolic content, DPPH radical scavenging activity (RSA), an ORAC assay, and a cellular antioxidant capacity (CAC) assay. The inhibitory effect of SM on oxidative stress-induced DNA damage in human leukocytes was evaluated by a Comet assay. The total phenolic content of raw SM extracted with methanol and of that extracted with water were significantly higher than the dried SM. Among the water extracts, the $IC_{50}$ for DPPH RSA of raw and sun-dried SM were significantly higher than that of oven-dried SM. Sun-dried SM showed the most potent ORAC value at 50 g/mL. The CAC against $AAPH^-$ induced oxidative stress in HepG2 cells, and $H_2O_2$ induced DNA damage were effectively protected against by all SM extracts. These results suggest that unprocessed SM are the best antioxidants, and that the sun-dried method would be the best option to use in terms of antioxidant activity and the antigenotoxic effect.

Effects of dietary Antrodia cinnamomea fermented product supplementation on metabolism pathways of antioxidant, inflammatory, and lipid metabolism pathways-a potential crosstalk

  • Lee, M.T.;Lin, W.C.;Lin, L.J.;Wang, S.Y.;Chang, S.C.;Lee, T.T.
    • Asian-Australasian Journal of Animal Sciences
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    • v.33 no.7
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    • pp.1167-1179
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    • 2020
  • Objective: This study was conducted to fathom the underlying mechanisms of nutrition intervention and redox sensitive transcription factors regulated by Antrodia cinnamomea fermented product (FAC) dietary supplementation in broiler chickens. Methods: Four hundreds d-old broilers (41±0.5 g/bird) assigned to 5 groups were examined after consuming control diet, or control diet replaced with 5% wheat bran (WB), 10% WB, 5% FAC, and 10% FAC. Liver mRNA expression of antioxidant, inflammatory and lipid metabolism pathways were analyzed. Prostaglandin E2 (PGE2) concentration in each group were tested in the chicken peripheral blood mononuclear cells (cPBMCs) of 35-d old broilers to represent the stress level of the chickens. Furthermore, these cells were stimulated with 2,2'-Azobis(2-amidinopropane) dihydrochloride (AAPH) and lipopolysaccharide (LPS) to evaluate the cell stress tolerance by measuring cell viability and oxidative species. Results: Heme oxygenase-1, glutathione S-transferase, glutamate-cysteine ligase, catalytic subunit, and superoxide dismutase, and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) that regulates the above antioxidant genes were all up-regulated significantly in FAC groups. Reactive oxygen species modulator protein 1 and NADPH oxygenase 1 were both rather down-regulated in 10% FAC group as comparison with two WB groups. Despite expressing higher level than control group, birds receiving diet containing FAC had significantly lower expression level in nuclear factor-kappa B (NF-κB) and other genes (inducible nitric oxide synthase, tumor necrosis factor-α, interleukin-1β, nucleotide-binding domain, leucine-richcontaining family, pyrin domain-containing-3, and cyclooxygenase 2) involving in inflammatory pathways. Additionally, except for 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase that showed relatively higher in both groups, the WB, lipoprotein lipase, Acetyl-CoA carboxylase, fatty acid synthase, fatty acid binding protein, fatty acid desaturase 2 and peroxisome proliferator-activated receptor alpha genes were expressed at higher levels in 10% FAC group. In support of above results, promoted Nrf2 and inhibited NF-κB nuclear translocation in chicken liver were found in FAC containing groups. H2O2 and NO levels induced by LPS and AAPH in cPBMCs were compromised in FAC containing diet. In 35-d-old birds, PGE2 production in cPBMCs was also suppressed by the FAC diet. Conclusion: FAC may promote Nrf2 antioxidant pathway and positively regulate lipid metabolism, both are potential inhibitor of NF-κB inflammatory pathway.

Effects of Fermented Kalopanax pictus on oxidative damage of neurofilament protein (신경세사 단백질의 산화적 손상에 엄나무 발효물이 미치는 영향)

  • Kang, Jung Hoon
    • Journal of the Korean Applied Science and Technology
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    • v.35 no.1
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    • pp.194-204
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    • 2018
  • This study was to investigate the effect of the extract(KP-HE) from Kalopanax pictus(KP) fermented with Hericium erinaceum(HE) mycelium on oxidative modification of neurofilament-L(NF-L) which is closely related to neurodegenerative disorders. The oxidative modification of NF-L was induced by AAPH producing peroxyl radicals in solution, and KP, HE, and KP-HE was investigated. KP and HE did not protect NF-L against peroxyl radical-mediated NF-L modification whereas KP-HE significantly prevented NF-L modification induced by peroxyl radical. KP-HE inhibited the formation of dityrosine in oxidative modification of NF-L and stimulated the peroxyl radical scavenging activity. The effects of KP, HE, and KP-HE on the modification of NF-L by tetrahydropapaveroline(THP), a neurotoxin found in patients with Parkinson's disease was investigated. KP-HE also prevented THP-mediated NF-L modification as compared to KP and HE. In addition, KP-HE significantly inhibited the formation of dityrosine in oxidative modified NF-L and enhanced the inhibition of reactive oxygen species(ROS) was generated by THP. The results suggested that KP-HE can contribute to protected cell from oxidative stress was induced by ROS and neurotoxin. Therefore, KP-HE could potentially be used as a valuable functional food ingredient to prevent neurodegenerative disorders.

Protective Effect of Angelica keiskei Juice and Oenanthe javanica DC Juice on Oxidative Stress (산화 스트레스에 대한 신선초 녹즙과 돌미나리 녹즙의 보호효과)

  • Lee, Doo-Jin;Lee, Jin-Ha;Lee, Ok-Hwan;Kim, Boh-Kyung;Park, Kun-Young;Kim, Jong-Dai
    • Korean Journal of Food Science and Technology
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    • v.47 no.4
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    • pp.517-524
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    • 2015
  • The objectives of the present study were to investigate the protective effects of Angelica keiskei juice and Oenanthe javanica juice against oxidative damage in LLC-$PK_1$ renal epithelial cells and to evaluate their free radical-scavenging activities. Both A. keiskei juice and O. javanica juice showed a strong in vitro antioxidant activities such as ${\alpha}$, ${\alpha}$-diphenyl-${\beta}$-picrylhydrazyl (DPPH), nitric oxide (NO), $O_2{^-}$, and ${\cdot}OH$ radical-scavenging activities. The LLC-$PK_1$ cells showed significant lipid peroxidation and cell death due to oxidative stress when it was induced by 2, 2'-azobis (2-amidinopropane) dihydrochloride (AAPH), sodium nitroprusside (SNP), pyrogallol, and 3-morpholinosydnonimine (SIN-1). Treatment with both A. keiskei juice and O. javanica juice significantly increased cell viability and inhibited lipid peroxidation. These results suggest that A. keiskei juice and O. javanica juice are potential natural antioxidants.