• Title/Summary/Keyword: heme oxygenase

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Anti-Oxidative and Anti-Inflammatory Effects of Malus huphensis, Ophiorrhiza cantonensis, and Psychotria rubra Ethanol Extracts (Malus huphensis, Ophiorrhiza cantonensis, Psychotria rubra 에탄올 추출물의 항산화 및 항염증 활성)

  • Jin, Kyong-Suk;Kwon, Hyun Ju;Kim, Byung Woo
    • Microbiology and Biotechnology Letters
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    • v.42 no.3
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    • pp.275-284
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    • 2014
  • This study was orchestrated with the purpose of uncovering new nutraceutical resources possessing biological activities in the plant kingdom. To fulfill our objective, we analyzed several Chinese plants and selected three possessing powerful anti-oxidative activities. The anti-oxidative and anti-inflammatory effects these three Chinese plants, Malus hupehensis, Ophiorrhiza cantonensis, and Psychotria rubra ethanol extracts were then evaluated. First of all, they possessed potent scavenging activity against 1,1-diphenyl-2-picryl hydrazyl, similar with that of ascorbic acid, used as a positive control. Moreover, they inhibited lipopolysaccharide (LPS)- and hydrogen peroxide-induced reactive oxygen species, in a dose-dependent manner, in RAW 264.7 cells. Also, they induced the expression of an anti-oxidative enzyme, heme oxygenase 1, and its upstream transcription factor, nuclear factor-E2-related factor 2. Furthermore, they suppressed LPS-induced nitric oxide (NO) formation, without cytotoxicity. The inhibition of NO formation was the result of the down regulation of inducible NO synthase (iNOS). The suppression of NO and iNOS by the three extracts might be the result of modulation by the upstream transcription factors, nuclear factor ${\kappa}B$ and activator protein-1. Taken together, these results indicate that these three Chinese plants possess potent anti-oxidative and anti-inflammatory activities. Therefore, they might be utilized as promising materials in the field of nutraceuticals.

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.

Studies on the Anti-inflammatory and Anti-apoptotic Effect of Catalposide Isolated from Catalpa ovata (개오동나무에서 추출(抽出)한 Catalposide의 항염(抗炎) 및 세포고사(細胞枯死) 억제효과(抑制效果)에 관(關)한 연구(硏究))

  • Oh, Cheon-Sik;Hwang, Sang-Wook;Kim, Yong-Woo;Song, Dal-Soo;Chae, Young-Seok;Jeong, Jong-Gil;Song, Ho-Joon;Shin, Min-Kyo
    • The Korea Journal of Herbology
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    • v.20 no.3
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    • pp.29-41
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    • 2005
  • Objectives : The use of natural products with therapeutic properties is as ancient as human civilisation and, for a long time, mineral, plant and animal products were the main sources of drugs. Catalposide, the major iridoid glycoside isolated from the stem bark of Catalpa ovata G. Don (Bignoniceae) has been shown to possess anti-microbial and anti-tumoral properties. Heme oxygenase-1 (HO-1) is a stress response protein and is known to play a protective role against the oxidative injury. In this study, we examined whether catalposide could protect Neuro 2A cells, a kind of neuronal cell lines, from oxidative damage through the induction of HO-1 protein expression and HO activity. We also examined the effects of catalposide on the productions of tumor necrosis $factor-{\alpha}\;(TNF-{\alpha})$ and nitric oxide (NO) on RAW 264.7 macrophages activated with the endotoxin lipopolysaccharide. Methods : HO-1 expression in Neuro 2A cells was measured by Western blotting analysis. NO and $TNF--{\alpha}$ produced by RAW 264.7 macrophage were measured by Griess reagent and enzyme-linked immunosorbent assay, respectively. Results : The treatment of the cells with catalposide resulted in dose- and time-dependent up-regulations of both HO-1 protein expression and HO activity. Catalposide protected the cells from hydrogen peroxide-induced cell death. The protective effect of catalposide on hydrogen peroxide-induced cell death was abrogated by zinc protoporphyrin IX, a HO inhibitor. Additional experiments revealed the involvement of CO in the cytoprotective effect of catalposide-induced HO-1. In addition, catalposide inhibited the productions of $TNF--{\alpha}$ and NO with significant decreases in mRNA levels of $TNF--{\alpha}$ and inducible NO synthase. Conclusions : Our results indicate that catalposide is a potent inducer of HO-1 and HO-1 induction is responsible for the catalposide-mediated cytoprotection against oxidative damage and that catalposide may have therapeutic potential in the control of inflammatory disorders.

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A Study on the Effect of Liriopis tuber water extract on Hydrogen Peroxide-stimulated C6 Astrocyte Cells (과산화수소 자극으로 활성화된 C6 성상교세포에 대한 맥문동추출물의 조절 효능 연구)

  • Park, Ki Ho;Kang, Seok Yong;Jung, Hyo Won;Park, Yong-Ki
    • The Korea Journal of Herbology
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    • v.35 no.4
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    • pp.9-16
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    • 2020
  • Objective : To identify the effects of the water extract of Liriope platyphylla tuber (Liriopis tuber, LT) on the activation of astocytes, we investigated the regulatory effects of LT extract on H2O2-induced oxidative damage in C6 rat astrocytes. Methods : LT extract was extracted with boiling water. C6 cell line were treated with LT extract at 1, 2, and 3 mg/㎖ or without for 30 min and then stimulated with H2O2 at 5 ㎛ for 24 hr. The cell viability was measured by MTT assay. The expression of glial fibrillary acidic protein (GFAP), signal transducer and activator of transcription 3 (STAT3), phospho-STAT3 (pSTAT3), cyclooxygenase (COX-2), Nuclear factor-κB (NF-κB), superoxide dismutase 2 (SOD2), heme oxygenase-1 (HO-1), catalase, Akt, phospho-Akt (p-Akt) phosphoinositide 3-kinases (PI3K), and protein kinase C alpha (PKCα) proteins were determined by Western blot, respectively. GFAP expression was also observed with immunocytochemistry under a fluorescence microscope. Results : LT extract induced cell proliferation in H2O2-stimulated C6 cells. LT extract significantly inhibited the expression of GFAP, NF-κB and COX-2 and increased the expression of HO-1 and the phosphorylation of STAT3 in H2O2-stimulated C6 cells. LT extract also significantly increased the phosphorylation of Akt and decreased the expression of PKCα in a dose-dependent manner in H2O2-stimulated C6 cells. Conclusions : LT extract can regulate H2O2-induced activation of astrocytes through inhibiting the expression of NF-κB, COX-2 and regulating Akt / HO-1, STAT3 or PKCα signaling pathway.

The Anti-Inflammatory Effects of Persicaria thunbergii Extracts on Lipopolysaccharide-Stimulated RAW264.7 Cells (Lipopolysaccharide로 처리 된 RAW264.7 세포에서 고마리 추출물의 항염증 효과)

  • Kim, Sang-Bo;Seong, Yeong-Ae;Jang, Hee-Jae;Kim, Gun-Do
    • Journal of Life Science
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    • v.21 no.12
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    • pp.1689-1697
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    • 2011
  • In this study, we investigated the anti-inflammation effect of Persicaria thunbergii (P. thunbergii) on RAW 264.7 murine macrophage cells. The anti-inflammatory activity of P. thunbergii was determined by measuring expression of the LPS-induced inflammatory proteins, inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and nuclear factor-${\kappa}B$ (NF-${\kappa}B$), and the production of nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$). Methanol extract of P. thunbergii decreased the expression of iNOS, COX-2 and NF-${\kappa}B$, and increased the expression of HO-1 in LPS-stimulated RAW264.7 cells. Methanol extract was fractioned by n-butanol, hexane and ethyl acetate (EtOAc) and each fraction was tested for inhibitory effects on inflammation. Among the sequential solvent fractions, the EtOAc soluble fraction was investigated by the expression of prostaglandin $E_2$ ($PGE_2$), and showed decreasing form to the dose-dependent manner. EtOAc extract showed the most effective inhibitory activity of the expression of iNOS, COX-2 and NF-${\kappa}B$, and the production of NO. The study showed that P. thunbergii has anti-inflammatory activity through the decrease of NO and inhibition of iNOS, COX-2, $PGE_2$ and NF-${\kappa}B$ expression, and by the increase of HO-1 enzyme. This study needs for more investigation to find out the most effective single compound with anti-inflammatory activity.

Anti-oxidative and Anti-inflammatory Activities of Decaisnea insignis Ethanol Extract (Decaisnea insignis 에탄올 추출물의 항산화 및 항염증 활성)

  • Jin, Kyong-Suk;Lee, Ji Young;Kwon, Hyun Ju;Kim, Byung Woo
    • Journal of Life Science
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    • v.24 no.9
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    • pp.973-980
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    • 2014
  • This study was conducted to explore new nutraceutical resources from the plant kingdom possessing biological activities. To fulfill this purpose, the anti-oxidative and anti-inflammatory activities of Decaisnea insignis ethanol extract (DIEE) were evaluated. First, DIEE possessed potent scavenging activity against 1,1-diphenyl-2-picryl hydrazyl (DPPH), similar to ascorbic acid used as a positive control. Moreover, DIEE inhibited lipopolysaccharide (LPS)- and hydrogen peroxide ($H_2O_2$)-induced reactive oxygen species (ROS) in RAW 264.7 cells. Furthermore, DIEE induced the expression of an anti-oxidative enzyme, heme oxygenase 1 (HO-1), and its upstream transcription factor, nuclear factor-E2-related factor 2 (Nrf2), in a dose-dependent manner. The modulation of the HO-1 and Nrf2 expressions might be regulated by mitogen-activated protein kinases (MAPKs) and their upstream signaling pathways. On the other hand, DIEE suppressed LPS-induced nitric oxide (NO) formation without cytotoxicity. The inhibition of the NO formation was the result of the downregulation of inducible NO synthase (iNOS) by DIEE. The suppression of NO and iNOS by DIEE might be modulated by their upstream transcription factors, nuclear factor ${\kappa}B$ ($NF-{\kappa}B$), and activator protein 1 (AP-1) pathways. Taken together, these results provide important new insights that D. insignis possesses anti-oxidative and anti-inflammatory activities. Therefore, it might be utilized as a promising material in the field of nutraceuticals.

Antioxidant Enzyme Activity and Anti-Adipogenic Effects of (-)-Epigallocatechin-3-Gallate in 3T3-L1 Cells ((-)-Epigallocatechin-3-Gallate의 3T3-L1 세포에서 항산화 효소 활성 및 지방세포 분화 억제 효과)

  • Kim, Younghwa
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.46 no.11
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    • pp.1293-1299
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    • 2017
  • Obesity contributes to the development of diseases, such as type II diabetes, hypertension, coronary heart disease, and cancer. In addition, oxidative stress caused by reactive oxygen species (ROS) is recognized widely as a contributing factor in the development of chronic diseases. This study was examined the antioxidant and anti-adipogenic activities of epigallocatechin-3-gallate (EGCG) in 3T3-L1 preadipocytes. 3T3-L1 cells were differentiated with or without EGCG for 6 days. The production of glutathione (GSH) and the activities of the antioxidant enzymes, such as glutathione reductase (GR), glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD) were measured. EGCG inhibited significantly the lipid accumulation and the expression of adipogenic specific proteins including CCAAT/enhancer binding protein ${\alpha}$ and adipocyte fatty acid binding protein. The production of intracellular ROS was decreased significantly by EGCG in 3T3-L1 cells. EGCG increased the GSH production and the activities of GPx, GR, CAT, and SOD. Moreover, EGCG increased the protein expression of glutamate-cysteine ligase and heme oxygenase-1 in 3T3-L1 cells. These results suggest that EGCG increased the activity and expression of antioxidant enzymes and suppressed the lipid accumulation in 3T3-L1 cells. Therefore, the use of phytochemicals that can maintain the GSH redox balance in adipose tissue could be promising for reducing obesity.

Effect of Moutan Cortex Radicis on Gene Expression Profile of Differentiated PC12 Rat Cells Oxidative-stressed with Hydrogen Peroxide (모단피의 PC12 cell 항산화 효과와 관련 HO, MIF, COMT 유전자 발현에 미치는 영향)

  • Son Mu Song;Rho Sam Woong;Ko Eun Jung;Na Youn Gin;Bae Hyun Su;Hong Moo Chang;Shin Min Kyu
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.17 no.4
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    • pp.905-913
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    • 2003
  • Oriental medicine explains aging as the weakening of Kidney-ai, and Kidney-strengthening herbal medicines such as Yukmijihwang-tang have been studied for anti-aging effects. In Western Medicine, the hypothesis that reactive oxidant species(ROS) contribute to the aging process is generally accepted. It has been reported that Moutan Cortex Radicis extract (MCR) was the most effective constituent of Yukmijihwang-tang in decreasing ROS production in oxidative-stressed cells. The purpose of this study is to confirm the anti-oxidant effect of MCR on PC12 cells, the expression of Heme oxygenase (HO), Macrophage migradon inhibitory factor (MIF), Catechol-O-methyltransferase (COMT) using real time RT PCR. PC12 cells were treated without or with hydrogen peroxide in the presence or absence of MCR using MTS assay. Hydrogen peroxide decreased the viability of PC12 cells by 53% and MCR did not influence that of stressed PC 12 cells irrespective of dose or incubation period. However, MCR showed an inhibitory effect on production of ROS in stressed cells, both dose and incubation time dependently. In particular, 1 ㎎/㎖ of MCR for 24 h culture almost returned to normal level. In the quantiation of anti-aging related gene expression, MCR at 1 ㎎/㎖ increased the expression of HO by 370%, MIF by 180% and COMT by 280% through real time RT PCR. In conclusion, MCR treatment protected PC12 cells from hydrogen peroxide and decreased ROS production and enhanced anti-oxidative gene expression such as HO, COMT and MIF, which suggests that MCR is involved in controlling anti-aging of nerve cells through elimination of cytotoxic stimuli.

The Effect of Haptoglobin on Expression of Inflammatory Cytokines in 3T3-L1 Preadipocytes. (3T3-L1 지방전구세포에서 합토글로빈에 의한 염증성 cytokine 발현 조절)

  • Cho, Jin-Kyung;Kim, Nam-Hoon;Oh, Mi-Kyung;Park, Seon-Joo;Kim, In-Sook
    • Journal of Life Science
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    • v.18 no.4
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    • pp.537-541
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    • 2008
  • White adipose tissue is now recognized as an important endocrine organ which secretes various signal factors and proteins termed 'adipokine'. Haptoglobin (Hp), which has been known as an acute phase protein, belongs to the adipokine. However, the function of Hp in adipose tissue remains unclear. To verify the role of Hp in preadipocytes, in this study, 3T3-L1 preadipocyte cells were stably transfected with human Hp gene and Hp-overexpressing cells were made. The Hp had no effect on cell growth of preadipocytes. By RT-PCR and Western blot analysis, the Hp inhibited gene expression of IL-6 and COX-2 and enhanced HO-1 synthesis in preadipocytes. Moreover, invasion assay showed the Hp suppressed migration of monocytes to preadipocytes. These findings suggest that the Hp may inhibit an inflammatory reaction in adipose tissue by regulating the expressions of pro-inflammatory and anti-inflammatory mediators, and by repressing monocytes/macrophages infiltration.

Similarities and differences between alpha-tocopherol and gamma-tocopherol in amelioration of inflammation, oxidative stress and pre-fibrosis in hyperglycemia induced acute kidney inflammation

  • Shin, Hanna;Eo, Hyeyoon;Lim, Yunsook
    • Nutrition Research and Practice
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    • v.10 no.1
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    • pp.33-41
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    • 2016
  • BACKGROUND/OBJECTIVES: Diabetes mellitus (DM) is a major chronic disease which increases global health problems. Diabetes-induced renal damage is associated with inflammation and fibrosis. Alpha (AT) and gamma-tocopherols (GT) have shown antioxidant and anti-inflammatory effects in inflammation-mediated injuries. The primary aim of this study was to investigate effects of AT and GT supplementations on hyperglycemia induced acute kidney inflammation in alloxan induced diabetic mice with different levels of fasting blood glucose (FBG). MATERIALS/METHODS: Diabetes was induced by injection of alloxan monohydrate (150 mg/kg, i.p) in ICR mice (5.5-week-old, male) and mice were subdivided according to their FBG levels and treated with different diets for 2 weeks; CON: non-diabetic mice, m-DMC: diabetic control mice with mild FBG levels (250 mg/dl ${\leq}$ FBG ${\leq}$ 450 mg/dl), m-AT: m-DM mice fed AT supplementation (35 mg/kg diet), m-GT: m-DM mice with GT supplementation (35 mg/kg diet), s-DMC: diabetic control mice with severe FBG levels (450 mg/dl < FBG), s-AT: s-DM mice with AT supplementation, s-GT: s-DM mice with GT supplementation. RESULTS: Both AT and GT supplementations showed similar beneficial effects on $NF{\kappa}B$ associated inflammatory response (phosphorylated inhibitory kappa B-${\alpha}$, interleukin-$1{\beta}$, C-reactive protein, monocyte chemotactic protein-1) and pre-fibrosis (tumor growth factor ${\beta}$-1 and protein kinase C-II) as well as an antioxidant emzyme, heme oxygenase-1 (HO-1) in diabetic mice. On the other hands, AT and GT showed different beneficial effects on kidney weight, FBG, and oxidative stress associated makers (malondialdehyde, glutathione peroxidase, and catalase) except HO-1. In particular, GT significantly preserved kidney weight in m-DM and improved FBG levels in s-DM and malondialdehyde and catalase in m- and s-DM, while AT significantly attenuated FBG levels in m-DM and improved glutathione peroxidase in m- and s-DM. CONCLUSIONS: the results suggest that AT and GT with similarities and differences would be considered as beneficial nutrients to modulate hyperglycemia induced acute renal inflammation. Further research with careful approach is needed to confirm beneficial effects of tocopherols in diabetes with different FBG levels for clinical applications.