• Title/Summary/Keyword: NOS-II

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Effects of Ginseng Radix plus Crataegi Fructus on the Gene Expression in Relation to Alzheimer's Disease. (인삼산사복합방(人蔘山査複合方)이 Alzheimer성 치매와 관련된 유전자 발현(發顯)에 미치는 영향)

  • Han, Sin-Hee;Kil, Gi-Jung
    • The Korea Journal of Herbology
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    • v.21 no.4
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    • pp.133-141
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    • 2006
  • Objectives : This research was investigated the effect of the Ginseng Radix plus Crataegi Fructus on the gene expression in relation to Alzheimer's disease. Methods : Observed gene expression of the Ginseng Radix plus Crataegi Fructus extract on $IL-1{\beta}$, IL-6, $TNF-{\alpha}$, COX-2, and NOS-II mRNA of BV2 microglia cell line treated with lipopolysacchride. Results : The Ginseng Radix plus Crataegi Fructus extract suppressed the gene expression of $IL-1{\beta}$, IL-6, $TNF-{\alpha}$, COX-2, NOS-II mRNA in BV2 microglia cell line treated with lipopolysacchride. Conclusion : These results suggest that the Ginseng Radix plus Crataegi Fructus extract may be effective for the prevention and treatment of Alzheimer's disease. Investigation into the clinical use of the Ginseng Radix plus Crataegi Fructus extract for Alzheimer's disease is suggested for future research.

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Anti-inflammatory Effects of Gagamtunong-san (가감투농산(加減透膿散)의 항염작용에 대한 실험적 연구)

  • Kim, Sang-Jin;Yoo, Dong-Youl
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.22 no.1
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    • pp.100-107
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    • 2008
  • The purpose of this research was to investigate the anti-inflammatory effects of Gagamtunong-san(GTNS) which has been medicated the patient such as mastitis. The results were as follows. The cytotoxicity on mouse lung fibroblast Cells(mLFC) was not served at all concentration of GTNS. GTNS in RAW264.7 cell inhibited $IL-1{\beta}$, IL-6, $TNF-{\alpha}$, COX-2 and NOS-II mRNA genes expression in a concentration-dependent manner. Specially GTNS inhibited NOS-II production very significantly at 100 ${\mu}g/ml$. GTNS inhibited NO production significantly in a concentration-dependent manner. GTNS inhibited ROS production in a concentration-dependent manner. GTNS inhibited $IL-1{\beta}$, IL-6 and $TNF-{\alpha}$ production significantly in serum of acute anti-inflammation-induced mice. GTNS increased the survival rate from the 3rd day on LPS-induced lethal endotoxemia. These results suggest that Gagamtunong-san(GTNS) can be useful in treating a lot of women mammary diseases caused by inflammation such as acute and chronic mastitis.

Arginase Inhibition by Ethylacetate Extract of Caesalpinia sappan Lignum Contributes to Activation of Endothelial Nitric Oxide Synthase

  • Shin, Woo-Sung;Cuong, To Dao;Lee, Jeong-Hyung;Min, Byung-Sun;Jeon, Byeong-Hwa;Lim, Hyun-Kyo;Ryoo, Sung-Woo
    • The Korean Journal of Physiology and Pharmacology
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    • v.15 no.3
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    • pp.123-128
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    • 2011
  • Caesalpinia sappan (C. sappan) is a medicinal plant used for promoting blood circulation and removing stasis. During a screening procedure on medicinal plants, the ethylacetate extract of the lignum of C. sappan (CLE) showed inhibitory activity on arginase which has recently been reported as a novel therapeutic target for the treatment of cardiovascular diseases such as atherosclerosis. CLE inhibited arginase II activity prepared from kidney lysate in a dose-dependent manner. In HUVECs, inhibition of arginase activity by CLE reciprocally increased NOx production through enhancement of eNOS dimer stability without any significant changes in the protein levels of eNOS and arginase II expression. Furthermore, CLE-dependent arginase inhibition resulted in increase of NO generation and decrease of superoxide production on endothelium of isolated mice aorta. These results indicate that CLE augments NO production on endothelium through inhibition of arginase activity, and may imply their usefulness for the treatment of cardiovascular diseases associated with endothelial dysfunction.

Rhamnogalacturonan I-rich fractions from cherry tomatoes stimulate phagocytosis in RAW 264.7 macrophages

  • Hwang, Dahyun;Lim, Young-Hee;Shin, Kwang-Soon;Koh, Jong-Ho
    • Korean Journal of Food Science and Technology
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    • v.51 no.3
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    • pp.278-285
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    • 2019
  • Tomato (Lycopersicon esculentum) is widely known for its beneficial effects on human health. To investigate the beneficial effects of polysaccharides from cherry tomato, cherry tomato polysaccharides (CTP) were prepared, the component sugars were analyzed, and the immunomodulatory activities in RAW 264.7 macrophages were assessed. CTP mainly contained arabinose (Ara) and galactose (Gal), suggesting that CTP might be enriched with an arabinogalactan (AG) moiety. The Ara and Gal present in CTP are likely components of AG-II (35.4%), namely $arabino-{\beta}-(3,6)-galactan$. To investigate the immunomodulatory activity of CTP, cytokine levels and iNOS2, COX-2, and $NF-{\kappa}B$ protein levels were analyzed, and $NF-{\kappa}B$ nuclear translocation and phagocytosis were observed by immunofluorescence. CTP significantly increased the levels of $TNF-{\alpha}$, MCP-1, and IL-6. CTP also increased iNOS2 and COX-2 expression as well as $NF-{\kappa}B$ nuclear translocation in RAW 264.7 cells. CTP significantly stimulated phagocytosis activity. These results showed that CTP stimulates macrophage activity, which can boost the innate immune response. CTP with high AG-II content could be used as a prebiotic to strengthen immunity.

Effect of aging on expression of nitric oxide and inducible nitric oxide synthase in human gingival fibroblasts (노화가 사람 치은섬유아세포의 nitric oxide와 inducible nitric oxide synthase 발현에 끼치는 영향)

  • Ji, Suk;Kook, Jung-Ki;Park, Joo-Cheol;Kim, Heung-Joong;Jang, Hyun-Seon;Kim, Chong-Kwan;Kim, Byung-Ock
    • Journal of Periodontal and Implant Science
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    • v.36 no.2
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    • pp.361-373
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    • 2006
  • 치주질환의 진행이 나이에 의해 영향을 받는다는 사실은 알려져 있으나 노화에 따른 치주조직 세포의 기능적인 변화에 관한 사실은 많이 알려져 있지 않다. 노화에 따른 세포의 노화가 치주질환의 진행에 어떠한 여향을 끼치는가를 아는 것은 중요하다. 염증 상태에서 nitric oxide (NO)는 조직 파괴에 관여하는 인자로 작용하여 치주질환의 진행에 관여하는 것으로 알려져 있다. 따라서 이 연구는 사람의 치은에서 배양된 치은섬유아세포를 이용하여 세포의 노화에 따른 NO와 이의 합성효소인 inducible nitric oxide synthase (iNOS)의 발현을 알아봄으로써 세포의 노화가 치주질환의 진행에 끼치는 영향에 대해 알아보고자 하였다. 10세의 환자와 55세의 환자에서 각각 채취한 치은에서 배양된 세포와 10세의 환자에서 채취한 세포를 계속적인 계대배양을 통해 얻은 실험실 상 노화된 세포를 포함하여 총 3 종류의 치은섬유세포를 실험에 이용하였다. Hot phenol-water extraction을 통해 추출된 Porphyromonas, gingivalis ATCC 33277 lipopolysaccharide (LPS)와 재조합 $IFN-{\gamma}$ 를 세포에 적용시켜 Griess assay를 통해 조건화된 배지에서 NO를 측정하였다. 20세와 55세의 환자에서 채취된 치은 조직과 총 3 종류의 배양된 세포에 NOS-II 항체를 적용시켜 iNOS 단백질 발현을 관찰하였다. Total RNA를 추출하여 RT-PCR를 통해 iNOS mRNA의 발현을 분석하였다. 치은섬유아세포에서 NO는 자발적으로 발생되었고, 이러한 발현은 젊은 세포보다 노화된 세포에서 강하였다. P, gingivalis LPS와 제조합 $IFN-{\gamma}$는 치은섬유아세포에서 NO의 발현을 증가시켰고, 이러한 발현은 젊은 세포보다 노화된 세포에서 강하였다. 면역조직화학 염색에서 iNOS 단백질은 젊은 사람과 노화된 사람의 치은 조직 모두에서 치은섬유아세포와 상피의 기저층 세포와 염증세포에서 발현되었으나 노화에 따른 발현의 차이를 구별할 수는 없었다. 세포의 면역염색에서 iNOS 단백질은 노화된 세포에서 강하게 발현되었고 이러한 발현은 LPS와 $IFN-{\gamma}$ 에 의해 강화되었다. LPS와 $INF-{\gamma}$ 의 조건이 주어지지 않은 상태에서 iNOS mRNA는 젊은 세포에서보다 노화된 세포에서 강하게 발현되었다. 이러한 결과를 통해 세포의 노화가 NO와 iNOS 발현을 증가시킴으로서 치주질환의 진행에 영향을 끼칠 수 있음을 시사하였다.

Intravenous administration of piceatannol, an arginase inhibitor, improves endothelial dysfunction in aged mice

  • Nguyen, Minh Cong;Ryoo, Sungwoo
    • The Korean Journal of Physiology and Pharmacology
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    • v.21 no.1
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    • pp.83-90
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    • 2017
  • Advanced age is one of the risk factors for vascular diseases that are mainly caused by impaired nitric oxide (NO) production. It has been demonstrated that endothelial arginase constrains the activity of endothelial nitric oxide synthase (eNOS) and limits NO generation. Hence, arginase inhibition is suggested to be vasoprotective in aging. In this study, we examined the effects of intravenous injection of Piceatannol, an arginase inhibitor, on aged mice. Our results show that Piceatannol administration reduced the blood pressure in aged mice by inhibiting arginase activity, which was associated with NO production and reactive oxygen species generation. In addition, Piceatannol administration recovered $Ca^{2+}$/calmodulin-dependent protein kinase II phosphorylation, eNOS phosphorylation and eNOS dimer stability in the aged mice. The improved NO signaling was shown to be effective in attenuating the phenylephrine-dependent contractile response and in enhancing the acetylcholine-dependent vasorelaxation response in aortic rings from the aged mice. These data suggest Piceatannol as a potential treatment for vascular disease.

The Effect of Varying Concentrations of Bee Venom Pharmacoupuncture Treatments on Type II Collagen Induced Arthritis in Mice (농도별 봉독약침이 생쥐의 Type II Collagen 유발 관절염에 미치는 영향)

  • Lee, Sung-Woo;Kim, Yu-Jong;Kim, Eun-Jung;Lee, Seung-Deok;Kim, Kap-Sung;Yoon, Jong-Hwa
    • Journal of Acupuncture Research
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    • v.29 no.1
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    • pp.75-87
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    • 2012
  • Objectives : The purpose of this study is to inquire into the effect of different concentrations of bee venom pharmacopuncture to inhibit genesis of pro-inflammatory cytokines and to inhibit nuclear factor (NF)-${\kappa}B$ activation on type II collagen induced arthritis. Methods : The experiment was divided into category of the normal group (NOR)-no treated group, control group (CON)-CIA (collagen induced arthritis) induced group, and 4,000 : 1 bee venom group (BV-L)- 4000:1 bee venom pharmacopuncture treated group after CIA, and 2000:1 bee venom group (BV-H)- 2,000 : 1 Bee venom pharmacopuncture treated group after CIA. RA was induced in the mice via injecting $50{\mu}{\ell}$ C II mixed CFA. The bee venom pharmacopuncture was applied on $ST_{35}$ for 19 days from the 3rd day of RA inducement. To research the effect on the expression of IKK ($I{\kappa}B$ kinase), iNOS (inducible nitric oxide synthase) & COX-2 (cyclooxygenase-2) mRNA, RT-PCR was performed on synovial membrane cells from the knee joint of CIA mice. Results : The PMA-induced $I{\kappa}B$ kinase (IKK), inducible nitric oxide synthase (iNOS) and cyclooxygenase -2 (COX-2) mRNA expression were dose-dependantly decreased in bee venom treated with synoviocytes. In mice treated with bee venom pharmacopuncture, foot thickness and the damage of synovial membranes of the joint was lessened, and the activation of RA-related pro-inflammatory cytokines such as MIF, TNF-${\alpha}$ and MMP-9 was significantly decreased. The activation of iNOS and COX-2 was suppressed by the inhibition of NF-${\kappa}B$. In addition, each data was shown that 2,000 : 1 bee venom pharmacopuncture was more effective than 4,000 : 1 bee venom pharmacopuncture. Conclusions : It is speculated that bee venom pharmacopuncture has the therapeutic effect of palliating the damage of the synovial membrane and inflammation on RA by suppressing of NF-${\kappa}B$ activation.

The Effectiveness of Ulmus Davidiana Planch Herbal Acupuncture to Inhibit $NF-{\kappa}B$ Activation on Type II Collagen-induced Arthritis in Mice (유근피(楡根皮) 약침의 $NF-{\kappa}B$ 활성 억제능이 생쥐의 Type II Collagen 유발 관절염에 미치는 영향)

  • Lee, A-Ram;Byun, Hyuk;Park, In-Shik;Jung, Chan-Yung;Kang, Min-Joo;Kim, Eun-Jung;Lee, Seung-Deok;Kim, Kap-Sung
    • Journal of Acupuncture Research
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    • v.24 no.6
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    • pp.15-27
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    • 2007
  • Objectives : The purpose of this study is to investigate the effectiveness of Ulmus davidiana Planch herbal acupuncture(UA) to inhibit nuclear $factor(NF)-{\kappa}B$ activation on type II collagen-induced arthritis (CIA) in mice. Methods : Using an in vitro test, the synoviocytes picked out from the experimental CIA mice were subcultured. The synoviocyte cells were treated with phorbol-12-myristate-13-acetate(PMA) for 1 hour prior to the addition of indicated concentrations($0.4\;-\;1.0mg/m{\ell}$) of UA, and the cells were further incubated for 24 hours. The in vivo test, $NF-{\kappa}B$ p65, inducible nitric oxide synthase(iNOS), cyclooxygenase-2(COX-2), vascular cell adhesion molecule(VCAM)-1 production and apoptosis was observed by immunohistochemical staining. Results : The PMA-induced $I{\kappa}B$ kinase(IKK), iNOS and COX-2 mRNA expression were dose-dependently decreased in UA treated synoviocytes. Using the in vivo test, the number of eosinophils in mice treated with UA noticeably decreased in the the CIA group(P<0.05 using student t test). In mice treated with UA, there was less cartilage erosion. less bone destruction, mild synovial hyperplasia, mild fibrosis, and mild angiogenesis with less MIP-2 production. By immunohistochemical staining, suppression of $NF-{\kappa}B$ p65, iNOS production, inhibition of COX-2 production, inhibition of VCAM-1 production and inducing apoptosis were observed. Conclusions : These results suggest that UA might be applicable to the therapy of RA to suppress $NF-{\kappa}B$ activation.

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Ginsenoside Rp1, a Ginsenoside Derivative, Blocks Promoter Activation of iNOS and COX-2 Genes by Suppression of an IKKβ-mediated NF-κB Pathway in HEK293 Cells

  • Shen, Ting;Lee, Jae-Hwi;Park, Myung-Hwan;Lee, Yong-Gyu;Rho, Ho-Sik;Kwak, Yi-Seong;Rhee, Man-Hee;Park, Yung-Chul;Cho, Jae-Youl
    • Journal of Ginseng Research
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    • v.35 no.2
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    • pp.200-208
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    • 2011
  • Ginsenoside (G) $Rp_1$ is a ginseng saponin derivative with anti-cancer and anti-inflammatory activities. In this study, we examined the mechanism by which G-$Rp_1$ inhibits inflammatory responses of cells. We did this using a strategy in which DNA constructs containing cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) promoters were transfected into HEK293 cells. G-$Rp_1$ strongly inhibited the promoter activities of COX-2 and iNOS; it also inhibited lipopolysaccharide induced upregulation of COX-2 and iNOS mRNA levels in RAW264.7 cells. In HEK293 cells G-$Rp_1$ did not suppress TANK binding kinase 1-, Toll-interleukin-1 receptor-domain-containing adapter-inducing interferon-${\beta}$ (TRIF)-, TRIF-related adaptor molecule (TRAM)-, or activation of interferon regulatory factor (IRF)-3 and nuclear factor (NF)-${\kappa}$B by the myeloid differentiation primary response gene (MyD88)-induced. However, G-$Rp_1$ strongly suppressed NF-${\kappa}$B activation induced by I${\kappa}$B kinase (IKK)${\beta}$ in HEK293 cells. Consistent with these results, G-$Rp_1$ substantially inhibited IKK${\beta}$-induced phosphorylation of $I{\kappa}B{\alpha}$ and p65. These results suggest that G-$Rp_1$ is a novel anti-inflammatory ginsenoside analog that can be used to treat IKK${\beta}$/NF-${\kappa}$B-mediated inflammatory diseases.

Gabexate mesilate ameliorates the neuropathic pain in a rat model by inhibition of proinflammatory cytokines and nitric oxide pathway via suppression of nuclear factor-κB

  • Oh, Seon Hee;Lee, Hyun Young;Ki, Young Joon;Kim, Sang Hun;Lim, Kyung Joon;Jung, Ki Tae
    • The Korean Journal of Pain
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    • v.33 no.1
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    • pp.30-39
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    • 2020
  • Background: This study examined the effects of gabexate mesilate on spinal nerve ligation (SNL)-induced neuropathic pain. To confirm the involvement of gabexate mesilate on neuroinflammation, we focused on the activation of nuclear factor-κB (NF-κB) and consequent the expression of proinflammatory cytokines and inducible nitric oxide synthase (iNOS). Methods: Male Sprague-Dawley rats were used for the study. After randomization into three groups: the sham-operation group, vehicle-treated group (administered normal saline as a control), and the gabexate group (administered gabexate mesilate 20 mg/kg), SNL was performed. At the 3rd day, mechanical allodynia was confirmed using von Frey filaments, and drugs were administered intraperitoneally daily according to the group. The paw withdrawal threshold (PWT) was examined on the 3rd, 7th, and 14th day. The expressions of p65 subunit of NF-κB, interleukin (IL)-1, IL-6, tumor necrosis factor-α, and iNOS were evaluated on the 7th and 14th day following SNL. Results: The PWT was significantly higher in the gabexate group compared with the vehicle-treated group (P < 0.05). The expressions of p65, proinflammatory cytokines, and iNOS significantly decreased in the gabexate group compared with the vehicle-treated group (P < 0.05) on the 7th day. On the 14th day, the expressions of p65 and iNOS showed lower levels, but those of the proinflammatory cytokines showed no significant differences. Conclusions: Gabexate mesilate increased PWT after SNL and attenuate the progress of mechanical allodynia. These results seem to be involved with the antiinflammatory effect of gabexate mesilate via inhibition of NF-κB, proinflammatory cytokines, and nitric oxide.