• 제목/요약/키워드: heme oxygenase-1

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위궤양 유발 마우스모델에서 강황(薑黃) 추출물의 위 보호 효과 (Gastroprotective Activity of Curcumae Longae Rhizoma against Gastric Ulcer in Mice)

  • 오민혁;김민주;신미래;박해진;서부일;노성수
    • 대한본초학회지
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    • 제35권3호
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    • pp.17-24
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    • 2020
  • Objectives : The objective of this study was to evaluate the gastric protective effect of Curcuma Longae Rhizoma (CLR) in 150 mM HCl/60% ethanol induced gastric ulcer (GU) in mice. Methods : Forty ICR mice were divided into five groups (n=8/Group): Nor group; Normal, Veh group; GU control, SC group; GU + sucralfate 10 mg/kg, CL; GU + CLR 30% ethanol extract 100 mg/kg, CH group; GU + CLR 30% ethanol extract 200 mg/kg. Then, mice were orally administered with 150 mM HCl/60% ethanol and caused GU. After 1 hr, mice were sacrificed, and blood and stomach tissue were collected. Results : CLR showed significance scavenging effects in 1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azinobis-3-ethyl-benzothiazoline-6-sulfonic acid (ABTS) radical scavenging activities (DPPH IC50; 78.18 ± 0.60 ㎍/㎖, ABTS IC50; 55.91 ± 1.86 ㎍/㎖). CLR significance reduce inflammatory-related factors such as cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), and interleukin-6 (IL-6) via nuclear factor kappa B (NF-κB) inactivation. In addition, the activation of nuclear factor erythroid2-related factor 2 (Nrf2) significantly led to up-regulation of anti-oxidant enzymes including factors heme oxygenase-1 (HO-1), super oxide dismutase (SOD), and glutathione peroxidase-1/2 (GPx-1/2). Conclusions : Our discovery provides that CLR possesses anti-oxidant and anti-inflammatory effects. Hence, CLR may ameliorate the development of gastric ulcer though the inhibition of NF-κB inflammatory pathway and the elevation of Nrf2 anti-oxidant pathway.

사물탕(四物湯) 가(加) 단참(丹參)의 상처 치료에 대한 효과 (The Effects of Samul-tang-ga-dansam for Wound Healing)

  • 이은별;김현지;김채영;최지수;우창훈;김영준;안희덕
    • 한방재활의학과학회지
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    • 제33권2호
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    • pp.1-18
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    • 2023
  • Objectives The purpose of this study was to evaluate the antioxidant, anti-inflammatory and wound healing effects of Samul-tang-ga-dansam water extract (SD) in wound-induced mice. Methods The mice were divided into five groups (n=7): the normal group, the control group, the positive control group, the low-dose SD group and the high-dose SD group. The normal group had no wounds and the other groups were wounded on the back with a leather punch. Distilled water was administered to the control group, 200 mg/kg of vitamin E was administered to the positive control group. In the low-dose SD group and the high-dose SD group, 1.23 g/kg and 2.47 g/kg of SD were administered, respectively. Antioxidant and anti-inflammatory protein levels were evaluated using western blot analysis. Skin tissue was analyzed by H&E, Masson's trichrome staining method. Results Oral administration of the SD significantly reduced the visible skin damage and decreased the reactive oxygen species and ONOO- activity of the serum. It significantly increased heme oxygenase-1, superoxide dismutase, catalase, GPx-1/2, Nrf2 and Keap-1 which are antioxidant-related factors in skin tissue and reduced NF-κB p65, inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor α, interleukin (IL)-1β, IL-6 which are inflammation-related factors. Also, SD significantly decreased NOX2, p22phox and p47phox and increased α-smooth muscle actin and COL1A1 protein expression in fibroblasts involved in connective tissue repair. According to histological examination, the thickened epithelial layer was thinned and collagen fibers were increased to accelerate wound healing. Conclusions It is suggested that Samul-tang-ga-dansam has antioxidant and anti-inflammatory effects and promotes wound tissue repair.

진무탕(眞武湯)이 MIA 유도 골관절염 흰쥐 모델에 미치는 영향 (Effects of Jinmu-tang on the Osteoarthritis by MIA in Rats)

  • 양두화;우창훈;안희덕
    • 한방재활의학과학회지
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    • 제28권1호
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    • pp.19-31
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    • 2018
  • Objectives The object of this study was to investigate the antioxidative and antiinflammatory effects of Jinmu-tang extract (JMT) on the Monosodium iodoacetate (MIA)-induced rat osteoarthritis. Methods To investigate the antioxidant capacities of JMT, we measured the total polyphenol and flavonoid, and 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-Azino-bis(3-ethyl-benzothiazoline-6-sulfonic acid) (ABTS) radical scavenging activity. To evaluate the antioxidative and antiinflammatory effects of JMT, the rats were divided into 5 groups (n=8). Normal group was not induced by MIA and treated at all (N), control group was induced by MIA and not treated at all (Con), positive control group was induced by MIA and orally administered indomethacin 5 mg/kg (Indo) and experimental groups were induced by MIA and orally administered JMT 100 mg/kg (JMT100) and JMT 200 mg/kg (JMT200) for 4 weeks. The changes of anti-type II collagen antibody in serum, heme oxygenase-1 (HO-1), phosphorylated inhibitor of ${\kappa}B{\alpha}$ ($p-I{\kappa}B{\alpha}$), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS) and tumor necrosis factor alpha ($TNF-{\alpha}$) in knee joint tissue and histopathological observation (Hematoxylin & Eosin and Safranin-O stain) were measured. Results Total polyphenol and flavonoid levels of JMT were $26.90{\pm}0.33mg/g$ and $6.02{\pm}0.34mg/g$. $IC_{50}$ of L-ascorbic acid and JMT of DPPH radical scavenging activity were $1.35{\pm}0.07{\mu}g/ml$ and $52.95{\pm}0.97{\mu}g/ml$. $IC_{50}$ of L-ascorbic acid and JMT of ABTS radical scavenging activity were $3.18{\pm}0.02{\mu}g/ml$ and $91.49{\pm}1.74{\mu}g/ml$. In serum, the anti-type II collagen antibody levels of JMT100 and JMT200 groups were decreased significantly. In knee joint tissue, the HO-1 level of JMT200 was increased significantly. The $p-I{\kappa}B{\alpha}$ and $TNF-{\alpha}$ levels of JMT200 were decreased significantly. The COX-2 and iNOS levels of JMT groups were decreased significantly. In histopathological observation, in comparison with Con, synovial tissue, cartilage and proteoglycan of JMT100 and JMT200 were well preserved. Conclusions According to the results, It is considered that JMT has antioxidant and antiinflammatory effects for MIA-induced rat osteoarthritis, so it could be applied to osteoarthritis treatment.

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) (Studies on the Anti-inflammatory and Anti-apoptotic Effect of Catalposide Isolated from Catalpa ovata)

  • 오천식;황상욱;김영우;송달수;채영석;정종길;송호준;신민교
    • 대한본초학회지
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    • 제20권3호
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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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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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    • 제10권1호
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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.

홍삼 비사포닌 분획의 단핵세포 분화와 염증반응에 대한 억제효과 (Non-saponin fraction of red ginseng inhibits monocyte-to-macrophage differentiation and inflammatory responses in vitro)

  • 강보빈;김채영;황지수;최현선
    • 한국식품과학회지
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    • 제51권1호
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    • pp.70-80
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    • 2019
  • 본 연구에서는 홍삼 비사포닌 분획(NSF)의 항 염증 효과를 마우스 대식세포와 인간유래 단핵세포에서 확인하였다. NSF는 마우스 대식세포에서 LPS로 유도된 NO, iNOS 그리고 COX-2의 양 뿐만 아니라 IL-6, $TNF-{\alpha}$, MCP-1과 같은 염증성 싸이토카인의 생성량을 유의적으로 감소시켰다. 인간 유래 단핵세포에서는 PMA에 의해 유도되는 대식세포로의 분화를 효과적으로 억제하면서 분화인자인 $CD11{\beta}$와 CD36의 발현을 유의적으로 감소시켰다. 마우스 대식세포에서와 마찬가지로 염증성 싸이토카인들의 생성량 또한 감소하였는데, 이러한 NSF의 항 염증 효과는 두 전사인자의 조절작용에 의한 것으로 사료된다. 즉 NSF는 $NF-{\kappa}B$의 핵으로 이동을 감소시킴으로써 전사활성을 억제하여 염증성 싸이토카인들의 발현을 저해하고 이와 반대로 Nrf2의 발현과 핵으로의 이동을 증가시켜 항산화 효소이면서 항 염증 작용을 나타내는 HO-1의 발현을 촉진하는 것으로 관찰되었다. 따라서 NSF는 $NF-{\kappa}B$와 Nrf2의 두 가지 신호전달체계를 조절함으로써 항 염증 작용을 나타냈으며 이를 홍삼 NSF의 항 염증 기작으로 보고하는 바이다.

RAW 264.7 대식세포에서 쑥부쟁이 추출물의 항산화 및 항염증 효능에 관한 연구 (Antioxidant and Anti-inflammatory Effects of Ethanol Extract of Aster yomena in RAW 264.7 Macrophages)

  • 김성옥;정지숙;최영현
    • 생명과학회지
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    • 제29권9호
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    • pp.977-985
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    • 2019
  • 쑥부쟁이는 국화과에 속하는 다년생 식물로서 다양한 질병의 예방 및 치료에 오랫동안 사용되어 왔다. 최근 연구에서 쑥부쟁이 잎 추출물이 항산화 및 항염증 효과가 있는 것으로 알려져 있지만, 정확한 효능 평가에 관한 연구는 여전히 미비한 실정이다. 본 연구에서는 RAW 264.7 대식세포에서 쑥부쟁이 잎 에탄올 추출물(EEAY)의 항산화 효능이 항염증 효능과 연관이 있는지의 여부를 조사하였다. 본 연구의 결과에 의하면, EEAY는 $H_2O_2$ 처리에 의한 RAW 264.7 세포의 세포 독성을 유의적으로 억제시켰으며, 이는 Nrf2 및 HO-1의 발현 증가와 관련이 있음을 보여 주었다. 또한 EEAY는 $H_2O_2$에 의한 apoptosis를 유의적으로 억제하였으며, 이는 caspase-3의 활성 억제에 따른 PARP의 분해 차단과 연관성이 있었다. 그리고 EEAY는 대표적인 항 염증성 사이토카인인 IL-10의 발현 및 생산을 증가시켰으며, 이는 전사 및 번역 수준에서의 TLR-4 및 Myd88 발현 증가와 관련이 있었다. 아울러 EEAY는 LPS에 의한 염증성 매개인자인 NO의 생성 증가를 현저히 억제하였으며, EEAY에 의한 NO 생성의 억제 효과는 HO-1 유도제인 hemin에 의해 더욱 증가되었다. 따라서 본 연구의 결과는 EEAY에 의한 산화적 및 염증성 스트레스에 대한 RAW 264.7 대식세포의 보호 효과에 최소한 Nrf2/HO-1 신호 경로의 활성화가 관여할 가능성을 보여주었다.

인진호 열수 추출물이 thioacetamide에 의해 유발된 간손상에 미치는 간보호 효과 (Protective effect of Artemisiae Capillaris Herba water extract on liver injury induced by thioacetamide)

  • 김민주;이진아;신미래;박해진;노성수
    • Journal of Nutrition and Health
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    • 제54권4호
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    • pp.412-421
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    • 2021
  • 본 연구는 TAA 복강투여로 유발된 간 손상 동물모델에서 인진호 열수 추출물의 간보호 효능을 평가하였으며 다음과 같은 결론을 얻었다. TAA로 인해 줄어드는 체중은 인진호 열수 추출물을 투여한 군에서 유의하게 증가하였으며, 간손상에 의해 증가한 혈중 암모니아 함량과 MPO 활성은 인진호 열수 추출물 투여군에서 유의하게 감소하였다. 간 조직의 western blotting 결과, 인진호 열수 추출물 투여가 산화적 스트레스 관련 인자들의 발현을 유의적으로 감소시키고, 항산화 관련 인자들의 발현을 유의하게 증가시켰으며, MMPs의 발현은 감소시키고 TIMP-1의 발현은 증가시킴을 확인할 수 있었다. 따라서 인진호 열수 추출물은 TAA로 유발된 간손상 동물모델에서 항산화 작용을 통해 산화적 스트레스를 억제하여 간보호 효과를 보이는 것으로 판단된다.

RAW264.7 대식세포에서 미선나무 잎 추출물의 항산화, 항염증 효능 및 기전연구 (Antioxidant and anti-inflammatory effects and mechanism of Abeliophyllum distichum leaf extract in RAW264.7 macrophages)

  • 유주희;김경아
    • Journal of Nutrition and Health
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    • 제56권5호
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    • pp.455-468
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    • 2023
  • 본 연구에서는 잠재적인 기능성 소재로의 개발 가능성을 검증하기 위하여 미선나무 잎 추출물의 항산화능과 항염증 효능을 확인하였다. 시료의 총 폴리페놀함량, DPPH 및 ABTS 라디칼 소거능, FRAP value를 측정하여 미선나무 잎 추출물의 항산화 활성을 확인하였으며 또한 RAW264.7 세포에 미선나무 잎 추출물 처리 후 HO-1의 발현이 증가하는 것을 통해 미선나무 잎 추출물의 항산화 기전을 확인하였다. 한편, LPS로 유도된 염증 상태의 RAW264.7 세포에서 미선나무 잎 추출물은 NF-κB 활성 억제를 통한 NO 생성 억제, iNOS, COX-2 발현 억제 및 염증성 사이토카인의 발현과 생성을 억제하는 것을 확인하였다. 이러한 본 연구 결과는 향후 미선나무 잎 추출물의 기능성 소재로의 개발을 위한 기초자료 마련에 그 의의가 있다.

부챗말 추출액이 $H_2O_2$에 의한 혈관내피세포주인 ECV304세포의 산화적 스트레스에 미치는 영향 (Effect of Padina arborescens on $H_2O_2$-induced Oxidative Stress in Human Endothelial Cell line, ECV304 cells)

  • 박진모;주성민;전병제;양현모;최한길;전병훈;김원신
    • 동의생리병리학회지
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    • 제22권6호
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    • pp.1431-1438
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    • 2008
  • The marine algae, Padina arborescens, have been used traditionally for treatment of various brain diseases. However, the molecular studies on the effect of Padina arborescens have not been carried out. In the present study, the protective effect of the water extract of Padina arborescens (PAWE) was researched in $H_2O_2$-treated human vascular endothelial cells, ECV304. ECV304 cells were pre-incubated with PAWE (0, 400, 800, 1,200 and $1,600{\mu}g/m{\ell}$) for 12 h and treated with 500 uM $H_2O_2$ for 12 h, and then the protective effects of PAWE were determined. PAWE recovered the $H_2O_2$-induced cell damage and decreased ROS production in ECV304 cells. Moreover, PAWE increased ERK expression and inhibited p38 and JNK expression. Furthermore, PAWE dosedependently increased the expression of heme oxygenase-1 (HO-1) and the HO-1 expression was reduced by ERK inhibitor treatment in $H_2O_2$-treated EVC304 cells. These results suggested that protective effect of PAWE on $H_2O_2$-induced oxidative stress in ECV304 cells might be associated with the production of HO-1 through the ERK signal pathway.