• Title/Summary/Keyword: COX-1, COX-2

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The Root from Heracleum moellendorffii Exerts Anti-Inflammatory Activity via the Inhibition of NF-κB and MAPK Signaling Activation in LPS-Stimulated RAW264.7 Cells

  • Park, Su Bin;Kim, Ha Na;Kim, Jeong Dong;Park, Gwang Hun;Son, Ho-Jun;Eo, Hyun Ji;Song, Jeong Ho;Jeong, Hyung Jin;Jeong, Jin Boo
    • Proceedings of the Plant Resources Society of Korea Conference
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    • 2018.10a
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    • pp.96-96
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    • 2018
  • Although the roots of Heracleum moellendorffii (HM-R) have been long treated for inflammatory human diseases, scientific evidence for the anti-inflammatory activity of HM-R is not sufficient. In this study, we investigated anti-inflammatory activity and mechanism of action of HM-R in LPS-stimulated RAW264.7 cells. HM-R blocked LPS-induced NO and PGE2 production, but not HM-L. HM-R inhibited LPS-induced overexpression of iNOS, COX-2, $IL-1{\beta}$ and IL-6 in RAW264.7 cells. HM-R inhibited LPS-induced $NF-{\kappa}B$ signaling activation through blocking $I{\kappa}B-{\alpha}$ degradation and p65 nuclear accumulation. In addition, HM-R inhibited MAPK signaling activation by attenuating the phosphorylation of ERK1/2, p38 and JNK. Furthermore, HM-R inhibited attenuated LPS-mediated overexpression of the osteoclast-specific factors such as NFATc1, cathepsin K, MCP-1 and TRAP. These results indicate that HM-R may exert anti-inflammatory activity by inhibiting $NF-{\kappa}B$ and MAPK signaling activation. From these findings, HM-R has potential to be a candidate for the development of chemopreventive or therapeutic agents for the inflammation and inflammatory diseases.

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Prognostic Factors for Node-Negative Advanced Gastric Cancer after Curative Gastrectomy

  • Lee, Eun Woo;Lee, Woo Yong;Koo, Ho-Seok
    • Journal of Gastric Cancer
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    • v.16 no.3
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    • pp.161-166
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    • 2016
  • Purpose: Lymph node (LN) metastasis is the best prognostic indicator in non-distant metastatic advanced gastric cancer. This study aimed to assess the prognostic value of various clinicopathologic factors in node-negative advanced gastric cancer. Materials and Methods: We retrospectively analyzed the clinical records of 254 patients with primary node-negative stage T2~4 gastric cancer. These patients were selected from a pool of 1,890 patients who underwent radical resection at Memorial Jin-Pok Kim Korea Gastric Cancer Center, Inje University Seoul Paik Hospital between 1998 and 2008. Results: Of the 254 patients, 128 patients (50.4%), 88 patients (34.6%), 37 patients (14.6%), and 1 patient (0.4%) had T2, T3, T4a, and T4b tumors, respectively. In a univariate analysis, operation type, T-stage, venous invasion, tumor size, and less than 15 LNs significantly correlated with tumor recurrence and cumulative overall survival. In a multivariate logistic regression analysis, tumor size, venous invasion, and less than 15 LNs significantly and independently correlated with recurrence. In a multivariate Cox proportional hazards analysis, tumor size (hazard ratio [HR]: 2.926; 95% confidence interval [CI]: 1.173~7.300; P=0.021), venous invasion (HR: 3.985; 95% CI: 1.401~11.338; P=0.010), and less than 15 LNs (HR: 0.092; 95% CI: 0.029~0.290; P<0.001) significantly correlated with overall survival. Conclusions: Node-negative gastric cancers recurred in 8.3% of the patients in our study. Tumor size, venous invasion, and less than 15 LNs reliably predicted recurrence as well as survival. Aggressive postoperative treatments and timely follow-ups should be considered in cases with these characteristics.

Study on the Anti-inflammatory Effect and Mechanism of Prunus mume Extract Regarding NF-κB (NF-κB 조절을 통한 오매추출물의 항염효과 및 작용기작에 관한 연구)

  • Seo, Won-Sang;Oh, Han-Na;Park, Woo-Jung;Um, Sang-Young;Lee, Dae-Woo;Kang, Sang-Mo
    • KSBB Journal
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    • v.29 no.1
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    • pp.50-57
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    • 2014
  • NF-${\kappa}B$ is a transcriptional factor which is involved in many biological processes including immunity, inflammation, and cell survival. Many investigators studied on the mechanism involved in activation of NF-${\kappa}B$ signalling pathway via ubiquitination and degradation of $I{\kappa}B$ regarding skin disease. Some specific molecules including Akt, MEK, p38 MAP Kinase, Stat3, et al. represent convergence points and key regulatory proteins in signaling pathways controlling cellular events such as growth and differentiation, energy homeostasis, and the response to stress and inflammation. Ultraviolet (UV) irradiation has many adverse effects on skin, including inflammation, alteration in the extracellular matrix, cellular senescence, apoptosis and skin cancer. Prunus mume, a naturally derived plant extract, has beneficial biological activities as blood fluidity improvement, anti-fatigue action, antioxidative and free radical scavenging activities, inhibiting the motility of Helicobacter pyolri. Previous reports on various beneficial function prompted us to investigate UVB-induced or other immunostimulated biological marker regarding P. mume extract. P. mume extract suppresses UVB-induced cyclooxygenase-2 (COX-2) expression in mouse skin epidermal JB6 P+ cells. The activation of activator protein-1 and nuclear factor-${\kappa}B$ induced by UVB was dose-dependently inhibited by P. mume extract treatment. This results suggest that P. mume extracts might be used as a potential agents for protection of inflammation or UVB induced skin damage.

Immunomodulatory Activity of Betulinic Acid by Producing Pro-Inflammatory Cytokines and Activation of Macrophages

  • Yun, Yun-Ha;Han, Shin-Ha;Park, Eun-Jung;Yim, Don-Sool;Lee, Sook-Yeon;Lee, Chong-kil;Cho, Kyung_Hae;Kim, Kyung_Jae
    • Archives of Pharmacal Research
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    • v.26 no.12
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    • pp.1087-1095
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    • 2003
  • Betulinic acid (BA), a pentacyclic triterpene isolated from Lycopus lucidus, has been reported to be a selective inducer of apoptosis in various human cancer and shown anti-inflammatory and immunomodulatory properties. We postulated that BA modulates the immunomodulatory properties at least two groups of protein mediators of inflammation, interlukin-1$\beta$ (IL-1$\beta$) and the tumor necrosis factor- $\alpha$ (TNF-$\alpha$) on the basis of the critical role of the monocytes and tissue macrophages in inflammatory and immune responses. TNF-$\alpha$ and IL-1$\beta$ were produced by BA in a dose dependent manner at concentration of 0.625 and 10 $\mu$g/mL. The production of NO associated with iNOS was inhibited when treated with LPS at the concentration of 2.5 to 20 $\mu$g/mL of BA whereas COX-2 expression was decreased at 2.5 to 20 $\mu$g/mL. These modulations of inflammatory mediators were examined in LPS-stimulated RAW 264.7 cells and peritoneal macrophages. The morphology of macrophage was also examined and enhanced surface CD 40 molecule was expressed when treated BA at 0.625∼5 $\mu$g/mL with or without LPS. Furthermore, BA (20 $\mu$g/mL) enhanced apoptosis by producing DNA ladder in the RAW 264.7 cells. Our results indicated that BA induced activation of macrophage and pro-inflammatory cytokines. This may provide a molecular basis for the ability of BA to mediate macrophage, suppress inflammation, and modulate the immune response.

Long-Term Outcomes in Stage I Lung Cancer After Segmentectomy with a Close Resection Margin

  • Kim, Dae Hyeon;Na, Kwon Joong;Park, In Kyu;Kang, Chang Hyun;Kim, Young Tae;Park, Samina
    • Journal of Chest Surgery
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    • v.54 no.5
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    • pp.361-368
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    • 2021
  • Background: In general, a 2-cm surgical margin is recommended for limited resection to obtain equivalent oncologic outcomes to lobectomy for lung cancer. This study aimed to examine the patterns of recurrence and prognostic factors for recurrence in patients with a close parenchymal resection margin. Methods: From January 2009 to April 2017, 156 patients with stage I lung cancer who underwent segmentectomy with a close resection margin (<2 cm) were enrolled. Recurrence-free survival and overall survival were assessed. In addition, predisposing factors for recurrence were evaluated. Results: The mean tumor size was 1.7±0.8 cm and the parenchymal resection margin was 1.1±0.6 cm. Recurrence developed in 17 (10.7%) of the 156 patients, and the 5-year recurrence-free survival rate was 88.9%. Distant metastasis (7.7%) was the predominant recurrence pattern. The isolated local recurrence rate was 1.9%. Multivariate Cox regression analysis revealed that age, tumor size, mediastinal lymph node dissection, postoperative complications, and histologic type were significant predisposing factors for recurrence. However, parenchymal margin distance did not significantly affect the long-term prognosis. Conclusion: Segmentectomy with a close resection margin for early-stage lung cancer in selected patients resulted in acceptable recurrence and survival. However, patients with tumors larger than 2 cm, squamous cell carcinoma histology, and insufficient mediastinal evaluation should be carefully followed up for recurrence.

Predictors of Avascular Necrosis after Kidney Transplantation

  • Ko, Young Min;Kwon, Hyunwook;Chun, Sung Jin;Kim, Young Hoon;Choi, Ji Yoon;Shin, Sung;Jung, Joo Hee;Park, Su-Kil;Han, Duck Jong
    • Korean Journal of Transplantation
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    • v.31 no.4
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    • pp.200-206
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    • 2017
  • Background: Risk factors for bone avascular necrosis (AVN), a common late complication after kidney transplantation (KT), are not well known. Methods: Patients that underwent living-donor KT at Asan Medical Center between January 2009 and July 2016 were included in this retrospective study to determine the incidence and risk factors for AVN after KT. Results: Among 1,570 patients that underwent living-donor KT, 33 (2.1%) developed AVN during a mean follow-up of 49.8±25.0 months. Additionally, AVN was diagnosed at a mean of 13.9±6.6 months after KT. The mean cumulative corticosteroid dose during the last follow-up in patients without AVN (9,108±3,400 mg) was higher than that that in patients with AVN (4,483±1,114 mg) until AVN development (P<0.01). More patients among those with AVN (n=4, 12.1%) underwent steroid pulse treatment because of biopsy-proven rejections during the first 6 months after KT than patients without AVN (n=68, 4.4%; P=0.04). Female (hazard ratio [HR], 2.29; P=0.04) and steroid pulse treatment during the first 6 months (HR, 2.31; P=0.02) were significant AVN risk factors as revealed by the Cox proportional multivariate analysis. However, no significant differences in rejection-free graft survival rates were observed between the two groups (P=0.67). Conclusions: Steroid pulse treatment within 6 months of KT and being female were independent risk factors for AVN development.

An Experimental Study on the Antioxidant and Anti-inflammatory Effects of Goryeon-hwa (고련환(苦練丸)의 항산화 및 항염증 효과에 관한 실험 연구)

  • Ye-Seul Yun;Seung-Jeong Yang;Seong-Hee Cho
    • The Journal of Korean Obstetrics and Gynecology
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    • v.37 no.2
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    • pp.1-16
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    • 2024
  • Objectives: The purpose of this study is to evaluate the antioxidant and anti-inflammatory effects of Goryeon-hwan (GRH), which is mentioned in ≪Donguibogam≫ that treats leukorrhea. Methods: In this study, the antioxidant efficacy of GRH was evaluated by measuring the total polyphenol and flavonoid content, DPPH radical scavenging activity, ABTS radical scavenging activity, and ROS production through RAW264.7 cells. The concentration of GRH cytotoxicity was confirmed through the cell viability of RAW264.7 cells, and the production of NO, the production of Cytokine through ELISA assay, and the expression of genes through Real-time PCR were measured to evaluate anti-inflammatory efficacy. Protein phosphorylation and protein expression were measured through Western blot analysis. Results: As a result of the experiment, GRH contained polyphenol and flavonoid, and concentration-dependent increased DPPH radical scavenging activity and ABTS radical scavenging activity and decreased ROS production. The anti-inflammatory efficacy measurement results showed a significant decrease in NO and Cytokine production in the GRH administration group compared to the control group. In terms of gene expression and protein expression, there was a significant decrease in iNOS, COX-2, IL-1β, IL-6, and TNF-α depending on the concentration, and a significant increase in HO-1 and NQO1. Protein phosphorylation measurements showed a concentration-dependent significant decrease in the GRH group at ERK and p38. Conclusions: As a result, the study experimentally confirmed the antioxidant and anti-inflammatory effects of GRH, suggesting that it may be used as a treatment for various gynecological inflammatory diseases including vaginitis.

Effects of Bee Venom and Cervi Cornu Parvum Pharmacoacupuncture in Monosodium Iodoacetate(MIA)-Induced Osteoarthritis Rat (봉독약침과 녹용약침이 MIA 유도 골관절염 흰쥐에 미치는 영향)

  • Kim, Whan-Young;Choi, Jin-Bong
    • Journal of Korean Medicine Rehabilitation
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    • v.20 no.1
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    • pp.61-77
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    • 2010
  • Objectives : The purpose of this study was to investigate the effects of Bee Venom (BV) and Cervi Cornu Parvum pharmacoacupuncture (CC) in monosodium iodide induced arthritis rats. Methods : The subjects were divided into 5 groups ; Normal, Control (no treatment after MIA), BV (Bee Venom pharmacoacupuncture $100{\mu}{\ell}$ daily at Dokbi (ST35) after inducing MIA), CC (Cervi Cornu Parvum pharmacoacupuncture $100{\mu}{\ell}$ dailyat Dokbi (ST35) after inducing MIA) and BV+CC (Bee Venom pharmacoacupuncture and Cervi Cornu Parvum pharmacoacupuncture $100{\mu}{\ell}$daily at Dokbi (ST35) after inducing MIA). After each operation, the present author observed the motor behavior recovery, hematological (Prostaglandin E2, AST, ALT), histological and immunological changes. Rats were tested at the 7th, 14th and 21st day. Results : Results are as follows. 1. All the experimental groups were improved compared with control group in plantar test. 2. All the experimental groups were improved compared with control group in touch test for sensory evaluator. 3. All the experimental groups were significantly decreased compared with control group in prostaglandin E2. 4. In histological observations, knee joint in all the experimental groups were improved compared with control group. 5. In immunological observations, all the experimental groups were significantly decreased compared with control group in COX-1, 2. Conclusions : It can be suggested that Bee venom and Cervi Cornu Parvum pharmacoacupuncture may improve motor behavior, hematological, histological and immunological findings in MIA-induced osetoarthritis rats. Especially, combination of these two treatments will be somewhat better in osteoarthritis recovery and motor function improvement.

Acacia ferruginea Inhibits Tumor Progression by Regulating Inflammatory Mediators-(TNF-α, iNOS, COX-2, IL-1β, IL-6, IFN-γ, IL-2, GM-CSF) and Pro-Angiogenic Growth Factor-VEGF

  • Sakthivel, Kunnathur Murugesan;Guruvayoorappan, Chandrasekaran
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.6
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    • pp.3909-3919
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    • 2013
  • The aim of the present investigation was to evaluate the effect of A ferruginea extract on Dalton's lymphoma ascites (DLA) induced tumours in BALB/c mice. Experimental animals received A ferruginea extract (10 mg/kg.b.wt) intraperitoneally for 14 consecutive days after DLA tumor challenge. Treatment with extract significantly increased the life span, total white blood cell (WBC) count and haemoglobin (Hb) content and decreased the level of serum aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), gamma glutamyl transferase (${\gamma}$-GT) and nitric oxide (NO) in DLA bearing ascites tumor models. In addition, administration of extract significantly decreased the tumour volume and body weight in a DLA bearing solid tumor model. The levels of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-${\alpha}$), interleukin-1 beta (IL-$1{\beta}$), interleukin-6 (IL-6) and granulocyte monocyte-colony stimulating factor (GM-CSF), as well as pro-angiogenic growth factors such as vascular endothelial growth factor (VEGF) and inducible nitric oxide synthase (iNOS) were elevated in solid tumour controls, but significantly reduced by A ferruginea administration. On the other hand, the extract stimulated the production of interleukin-2 (IL-2) and interferon-gamma (IFN-${\gamma}$) in animals with DLA induced solid tumours. Increase in $CD4^+$ T-cell population suggested strong immunostimulant activity for this extract. GC/MS and LC/MS analysis showed quinone, quinoline, imidazolidine, pyrrolidine, cyclopentenone, thiazole, pyrazole, catechin and coumarin derivatives as major compounds present in the A ferruginea methanolic extract. Thus, the outcome of the present study suggests that A ferruginea extract has immunomodulatory and tumor inhibitory activities and has the potential to be developed as a natural anticancer agent.

Comparison of Marker Components and Biological Activities of Gamiguibi-tang(Jiaweiguipi-tang) Decoction and Commercial Extract Granules (가미귀비탕 탕액과 시판제제의 성분 및 생리활성 비교)

  • Kim, Jung Ok;Baek, Ka Yeon;Lee, Hwa Dong
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.32 no.5
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    • pp.333-340
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    • 2018
  • Gamiguibi-tang (GGBT) is a traditional herbal medicine generally used to treat anemia, insomnia, anxiety, and nervousness. GGBT is being commercially produced in the form of extract granule and the quality control methods are specified in the Korean Herbal Pharmacopeia (KHP). However, there is no method to simultaneously analyze compound preparations. In this study, a HPLC method was developed and validated for the simultaneous determination of marker compounds in GGBT. And the contents of marker components and biological activities of the commercial GGBT extract granules (GGBT-2 and GGBT-3) were compared with those of the GGBT decoction (GGBT-1). We confirmed the robustness of simultaneous analytical method by monitoring the contents of the commercial GGBT products and carrying out validation. The marker components of GGBT were geniposide ($8.03{\sim}12.70{\mu}g/mL$), paeoniflorin ($2.79{\sim}4.25{\mu}g/mL$) and glycyrrhizic acid ($5.06{\sim}6.30{\mu}g/mL$). DPPH and ABTS radical scavenging activities were 47.34~63.17% and 21.52~33.61% in the GGBT products concentration of $1,000{\mu}g/mL$, respectively. The GGBT products significantly decreased NO, iNOS and COX-2 production in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages in a concentration-dependent manner. The GGBT-2 had higher contents of marker components and biological activities than GGBT-1 and GGBT-3. The research suggest that be used in developing quality control methods for enhancing the quality of herbal medicines.