• Title/Summary/Keyword: Inducible nitric oxide

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Anti-inflammatory Effect of Gagam-GongJin-dan in mouse peritoneal macrophages (마우스 복강대식세포에서 가감공진단(加減拱辰丹)의 항염증 효과)

  • Kim, Hong-Jun;Kim, Young-Sik;Mok, Ji-Ye;Jeong, Seung-Il;Hwang, Sung-Yeoun;Cho, Jung-Keun;Jang, Seon-Il
    • Herbal Formula Science
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    • v.19 no.1
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    • pp.207-217
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    • 2011
  • Objectives : In a previous study, we have shown that Gagam-Gongjin-Dan(GGD) has an inhibitory effect on the ovalbumin-induced immune responses and a hepatoprotective effect on actaminophen-induced liver injury in Balb/c Mice. However, the possible anti-inflammatory effect of GGD extract for inflammatory mediators was not reported. Therefore, the purpose of this study was to investigate an inhibitory effects of GGD extract against lipopolysaccharides(LPS) induced inflammatory mediators in mouse peritoneal macrophages. Methods : GGD extract was prepared by extracting with methanol for 7 days. The extract was freeze-dried following filtration through vacuum distillation system. Accumulated nitrite, an oxidative product of nitric oxide(NO), was measured in the culture medium by the Griess reaction. The levels of prostaglandin $E_2(PGE_2)$, interleukin-$1{\beta}$(IL-$1{\beta}$), tumor necrosis factor-${\alpha}$(TNF-${\alpha}$) were measured by enzyme-linked immunosorbent assay. The expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2(COX-2) were measured by Western blot analysis. Results : GGD extract (50-$400\;{\mu}g$/ml) per se had no cytotoxic effect in LPS-stimulated peritoneal macrophages. GGD extract dose-dependently reduced NO, $PGE_2$, IL-$1{\beta}$ and TNF-${\alpha}$ production and COX-2 activity caused by stimulation of LPS. The levels of iNOS and COX-2 protein expressions were markedly suppressed by the treatment with GGD extract in a dose dependent manner. Conclusions : These results suggest that GGD extract has an anti-inflammatory effect against LPS-induced inflammatory mediators in peritoneal macrophages, these properties may contribute to inflammation disease care.

Antioxidative and Anti-inflammatory Effects of Extracts from Different Organs of Cirsium japonicum var. ussuriense (엉겅퀴(Cirsium japonicum var. ussuriense) 부위별 추출물의 항산화 및 항염증 효과)

  • Mok, Ji-Ye;Kang, Hyun-Ju;Cho, Jung-Keun;Jeon, In-Hwa;Kim, Hyeon-Soo;Park, Ji-Min;Jeong, Seung-Il;Shim, Jae-Suk;Jang, Seon-Il
    • The Korea Journal of Herbology
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    • v.26 no.4
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    • pp.39-47
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    • 2011
  • Objective: The roots, leaves, flowers, stems and seeds of Cirsium japonicum var. ussuriense are often used in treatment of human diseases such as hemorrhage, blood congestion and inflammation. Focusing our attention on natural and bioavailable sources of antioxidants and anti-inflammation, we undertook to investigate the antioxidant and anti-inflammatory properties of Cirsium japonicum var. ussuriense used as a folk medicine in Korea. Methods: The extracts of the leaves, stems, flowers, seeds and roots from C. japonicum var. ussuriense were prepared by extracting with water or 80% ethanol. Total flavonoids and polyphenols were measured by a colorimetric assay. The free radical scavenging activity of the extract was analyzed by the DPPH (1,1-diphenyl-2-picryl hydrazyl), ABTS (2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) and Griess reagent assay. An oxidative product of nitric oxide (NO), was measured in the culture medium by the Griess reaction. The level of prostaglandin $E_2$ ($PGE_2$) was measured by enzyme-linked immunosorbent assay. The expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were measured by Western blot analysis. Results: Total flavonoid and polyphenol amounts of the leaves (CLE) and flowers (CFE) showed higher than those of the seed extract (CSE), stem extract (CSTE) and roots (CRE). CLE and CFE also showed the high antioxidant activities such as DPPH, NO-like and ABTS radical scavenging activity. An antioxidant activities of these water extracts showed higher than those of 80% ethanol extracts. We investigated the anti-inflammatory effects of CLE on lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. CLE significantly suppressed the levels of the inflammatory mediators such as NO and prostaglandin $E_2$ ($PGE_2$) in dose dependant. Furthermore, the levels of iNOS and COX-2 protein expressions were markedly suppressed by the treatment with CLE extract in a dose dependent manner. Conclusions: These results suggest that CLE water extract has a higher anoxidant and anti-inflammatory activity, these properties may contribute to the oxidative and inflammatory related disease care.

Cell migration and Anti-inflammatory Effect of Red Ginseng Extracts Fermented with Laetiporus Sulphureus (붉은덕다리버섯 균사체로 발효한 홍삼 배양액의 cell migration 및 항염 효능에 관한 연구)

  • Oh, Seong-Hwa;Choi, Soo-Yeon;Lee, Nu Rim;Lee, Jung No;Kim, Dong-Seok;Lee, Sang-Hwa;Park, Sung-Min
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.40 no.3
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    • pp.297-305
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    • 2014
  • Red ginseng (RG) contains specific ginsenosides (Rg2, Rg3) which show various pharmacological effects and absorption rate in the body better than panax ginseng. Therefore many people have been used it for health for a long time. Furthermore, many researchers have been studying its biological activities for a long times because fermentation generates lots of beneficial small molecules good for health. In this study, we fermented red ginseng with mycelium of Leatiporus sulphures var. miniatus for 7 days. As a result, we found that three ginsenosides Rg1, Re and Rb2 were decreased from 0.24, 0.25, 0.16 mg/g to 0.12, 0.1, 0.03 mg/g respectively HPLC analysis. In addition, we studied biological activities of fermented red ginseng (FRG) about skin ageing such as anti-inflammation, cell migration, anti-oxidation, collagen type 1 synthesis, and MMP-1 inhibition activities. As a result, FRG were shown higher anti-inflammatory and cell migration promoting activities than RG. FRG inhibited production of nitric oxide (NO) and mRNA expression of inducible nitric oxide synthase (iNOS) and decreased interleukin (IL)-6 induced by LPS stimulation in RAW 264.7 cells. In conclusion, this study suggest that FRG could be a potential source as a new natural anti-inflammatory agent.

Agastache rugosa Leaf Extract Inhibits the iNOS Expression in ROS 17/2.8 Cells Activated with TNF-$\alpha$ and IL-$\beta$

  • Oh Hwa Min;Kang Young Jin;Kim Sun Hee;Lee Young Soo;Park Min Kyu;Heo Ja Myung;Sun Jin Ji;Kim Hyo Jung;Kang Eun Sil;Kim Hye Jung;Sea Han Geuk;Lee Jae Heun;YunChoi Hye Sook
    • Archives of Pharmacal Research
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    • v.28 no.3
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    • pp.305-310
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    • 2005
  • It has been suggested that nitric oxide (NO) derived from inducible nitric oxide synthase (iNOS) may act as a mediator of cytokine-induced effects on bone turn-over. NO is also recognized as an important factor in bone remodeling, i.e., participating in osteoblast apoptosis in an arthritic joint. The components of Agastache rugosa are known to have many pharmacological activities. In the present study, we investigated the effects of Agastache rugosa leaf extract (ELAR) on NO production and the iNOS expression in ROS 17/2.8 cells activated by a mixture of inflammatory cytokines including TNF-$alpha$ and IL-1$\beta$. A preincubation with ELAR significantly and concentration-dependently reduced the expression of iNOS protein in ROS 17/2.8 cells activated with the cytokine mixture. Consequently, the NO production was also significantly reduced by ELAR with an IC$_{50}$ of 0.75 mg/mL. The inhibitory mechanism of iNOS induction by ELAR prevented the activation and translocation of NF-$\kappa$B (p65) to the nucleus from the cytosol fraction. Furthermore, ELAR concentration-dependently reduced the cellular toxicity induced by sodium nitroprusside, an NO-donor. These results suggest that ELAR may be beneficial in NO-mediated inflammatory conditions such as osteoporosis.

Black ginseng-enriched Chong-Myung-Tang extracts improve spatial learning behavior in rats and elicit anti-inflammatory effects in vitro

  • Saba, Evelyn;Jeong, Da-Hye;Roh, Seong-Soo;Kim, Seung-Hyung;Kim, Sung-Dae;Kim, Hyun-Kyoung;Rhee, Man-Hee
    • Journal of Ginseng Research
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    • v.41 no.2
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    • pp.151-158
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    • 2017
  • Background: Chong-Myung-Tang (CMT) extract is widely used in Korea as a traditional herbal tonic for increasing memory capacity in high-school students and also for numerous body ailments since centuries. The use of CMT to improve the learning capacity has been attributed to various plant constituents, especially black ginseng, in it. Therefore, in this study, we have first investigated whether black ginseng-enriched CMT extracts affected spatial learning using the Morris water maze (MWM) test. Their molecular mechanism of action underlying improvement of learning and memory was examined in vitro. Methods: We used two types of black ginseng-enriched CMT extracts, designated as CM-1 and CM-2, and evaluated their efficacy in the MWM test for spatial learning behavior and their anti-inflammatory effects in BV2 microglial cells. Results: Our results show that both black ginseng-enriched CMT extracts improved the learning behavior in scopolamine-induced impairment in the water maze test. Moreover, these extracts also inhibited nitric oxide production in BV2 cells, with significant suppression of expression of proinflammatory cytokines, especially inducible nitric oxide synthase, cyclooxygenase-2, and $interleukin-1{\beta}$. The protein expression of mitogen-activated protein kinase and nuclear $factor-{\kappa}B$ pathway factors was also diminished by black ginseng-enriched CMT extracts, indicating that it not only improves the memory impairment, but also acts a potent anti-inflammatory agent for neuroinflammatory diseases. Conclusion: Our research for the first time provides the scientific evidence that consumption of black ginseng-enriched CMT extract as a brain tonic improves memory impairment. Thus, our study results can be taken as a reference for future neurobehavioral studies.

Anti-Inflammatory Effect of Sedum takesimense Nakai Water Extract in RAW 264.7 Cells (섬기린초 물 추출물의 마우스 대식세포에서 항염증 효능)

  • Jang, Ji Hun;Jung, Ho Kyung;Ko, Jae Hyung;Sim, Mi Ok;Woo, Kyeong Wan;Kim, Tae Muk;Lee, Ki Ho;Ahn, Byeong Kwan;Cho, Hyun Woo;Cho, Jung Hee;Jung, Won Seok
    • Korean Journal of Medicinal Crop Science
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    • v.24 no.3
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    • pp.228-236
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    • 2016
  • Background: Sedum takesimense Nakai has been used as folk medicine in Korea. The present study aimed to determine the biological activity of S. takesimense by investigating the anti-inflammatory effects of S. takesimense water extract (SKLC) on the lipopolysaccharide-induced inflammatory response in RAW 264.7 cells. Methods and Results: Cytotoxicity of SKLC on RAW 264.7 cells was determinded by performing MTS assay was found to have no cytotoxic effect on RAW 264.7 cells at a concentration range of $62-500{\mu}g/m{\ell}$. Further, pretreatment of SKLC inhibited lipopolysaccharide-induced nitric oxide (NO) production in a dose-dependent manner. To determined the inhibitory mechanisms of SKLC on inflammatory mediators, we assessed the inducible nitric oxide synthase (iNOS) and cyclooxygnease-2 (COX-2) pathways. The activities of these pathways were decreased in a dose-dependent manner by SKLC. The production of tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukin $(IL)-1{\beta}$, and IL-6 were also reduced. Conclusions: These results suggest that the down regulation of iNOS, COX-2, TNF-${\alpha}$, IL-$1{\beta}$, and IL-6 expression by SKLC are mediated by the down regulation of nuclear factor-${\kappa}B$ (NF-${\kappa}B$) activity, a transcription factor necessary for pro-inflammatory mediators. This might be the mechanism underlying the anti-inflammatory effects of SKLC.

Inhibition of inflammatory responses in lipopolysaccharide-induced RAW 264.7 cells by Pinus densiflora root extract

  • Lee, Jae-Eun;Lee, Eun-Ho;Park, Hye-Jin;Kim, Ye-Jin;Jung, Hee-Young;Ahn, Dong-Hyun;Cho, Young-Je
    • Journal of Applied Biological Chemistry
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    • v.61 no.3
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    • pp.275-281
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    • 2018
  • Pinus densiflora root (PDR) is used as a medicinal plant. In this study, we investigated whether the PDR extract has anti-inflammatory activities. Cell viability assays showed that the extract was not toxic toward RAW 264.7 cells at concentrations up to $10{\mu}g/mL$. At $10{\mu}g/mL$, the extract decreased nitric oxide (NO) content to 40% of the control level. The protein expression of inducible nitric oxide synthase (iNOS), which generates NO, decreased with increasing concentrations of the extract. Prostaglandin $E_2$ ($PGE_2$) levels were significantly inhibited by over 50% in the presence of $10{\mu}g/mL$ of the extract. The protein expression of cyclooxygenase-2 (COX-2), which generates $PGE_2$, decreased with increasing concentrations of the extract. Proinflammatory cytokines, such as tumor necrosis factor-alpha ($TNF-{\alpha}$), interleukin-6 (IL-6), and $IL-1{\beta}$, were detected in RAW 264.7 cells after lipopolysaccharide (LPS) treatment. The extract did not affect the levels of $TNF-{\alpha}$ and IL-6, but it significantly inhibited the level of $IL-1{\beta}$. It also completely inhibited the transcription of nuclear factor-kappaB ($NF-{\kappa}B$). These results indicate that the PDR extract reduces inflammatory response-related proteins, such as NO, $PGE_2$, iNOS, and COX-2, in LPS-induced RAW 264.7 cells via the regulation of $NF-{\kappa}B$. Consequently, we have provided a mechanism to explain the anti-inflammatory effect of the PDR extract; that is, it exerts such an effect by regulating $NF-{\kappa}B$. The PDR extract can therefore be considered as an effective anti-inflammatory agent.

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.

Anti-Inflammatory Activity of Austroinulin from Stevia rebaudiana in LPS-induced RAW264.7 Cells (스테비아로부터 분리한 Austroinulin의 RAW264.7 세포에 대한 항염증 효과)

  • Byun, Myung-Woo
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.41 no.4
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    • pp.456-461
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    • 2012
  • The leaves of $Stevia$ $rebaudiana$ are well-known in Japan, Korea, and China as a natural sweetener. Medicinal uses of this plant originated in Paraguay and Brazil in the form of aqueous decoctions of the leaves used as a contraceptive agent and for the treatment of hyperglycemia. In the present study, the antioxidant, anti-hypertension, and anti-inflammatory activities of $S.$ $rebaudiana$ extracts are investigated for their use in food. The biologically-active compound was isolated and purified from $S.$ $rebaudiana$. The isolated compound was identified as austroinulin ($C_{20}H_{34}O_3$; molecular weight 322) by mass, IR spectrophotometry, 1D, and 2D-NMR. Austroinulin was characterized as a diterpenoid possessing a 3-methylpenta-2,4-dienyl at C-9. When subjected to an inflammatory mediator inhibitory assay from lipopolysaccharide (LPS)-activated macrophages, the austroinulin inhibited the enhanced production of nitric oxide (NO) and inducible nitric oxide synthase (iNOS) expression (10 ${\mu}g$/mL=67.9 and 45.1%, respectively). This was significant and dose-dependent. The results suggest that austroinulin from $S.$ $rebaudiana$ inhibited the NO and iNOS in RAW 264.7 cells.

Immunomodulating Effect of Extract of Cheonggukjang Fermented with Bacillus amyloliquefaciens (SRCM100730) on RAW 264.7 Macrophages (Bacillus amyloliquefaciens(SRCM 100730)로 발효된 청국장 추출물의 RAW 264.7 대식세포 면역증강 활성)

  • Choo, Seung Bin;Yang, Hui;Jeong, Do-Yuon;Jeong, Seong-Yeop;Ryu, Myeong Seon;Oh, Kwang-Hoon;Yoo, Yung Choon
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.46 no.11
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    • pp.1300-1307
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    • 2017
  • Cheonggukjang is well known as a traditional fermented food in Korea and has various biological activity. In this study, immune-enhancing activity of extract of cheonggukjang fermented with Bacillus amyloliquefaciens (SRCM100730) was examined in RAW 264.7 murine macrophages. Treatment with extract augmented production of nitric oxide (NO) and tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$) from RAW 264.7 macrophages in a dose-dependent manner. Similarly, increased mRNA expression of inducible nitric oxide synthase (iNOS) and $TNF-{\alpha}$ was observed. In addition, the extract synergistically enhanced production of NO and $TNF-{\alpha}$ from lipopolysaccharide (LPS)-stimulated macrophages. Analysis of intracellular pathways revealed that the immune-enhancing activity of cheonggukjang extract was related to activation of mitogen-activated protein kinases (MAPK) and nuclear factor kappa-light-chain-enhancer of activated B cells ($NF-{\kappa}B$). These results suggest that cheonggukjang fermented with B. amyloliquefaciens (SRCM100730) is a beneficial food effective for activation of immune responses.