• Title/Summary/Keyword: Nuclear factor-kappa

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The Role of Yoga Intervention in the Treatment of Allergic Rhinitis: A Narrative Review and Proposed Model

  • Chauhan, Ripudaman Singh;Rajesh, S.K
    • CELLMED
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    • v.10 no.3
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    • pp.25.1-25.7
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    • 2020
  • Allergic Rhinitis (AR) is an IgE (immunoglobin-E) mediated inflammatory condition of upper respiratory tract; main clinical features involve runny nose, sneezing, nasal obstruction, itching and watery eyes. AR is a global problem and has large variations in incidences, currently affects up to 20% - 40% of the population worldwide. It may not be a life-threatening disease per se but indisposition from the condition can be severe and has the potential to adversely affect the daily functioning of life. Classical yoga literature indicates that, components of yoga have been used to treat numerous inflammatory conditions including upper respiratory tract. A few yoga intervention studies reported improvement in lung capacity, Nasal air flow and symptoms of allergic rhinitis. This review examined various anti-inflammatory pathways mediated through Yoga that include downregulation of pro-inflammatory cytokines and upregulation of anti-inflammatory cytokines. The hypothalaminic-pitutary-adrenal (HPA) axis and vagal efferent stimulation has been reported to mediate anti-inflammatory effect. A significant reduction is also reported in other inflammatory biomarkers like- TNF-alpha, nuclear factor kappa B (NF-κB), plasma CRP and Cortisol level. Neti, a yogic nasal cleansing technique, reported beneficial effect on AR by direct physical cleansing of thick mucus, allergens, and inflammatory mediator from nasal mucosa resulting in improved ciliary beat frequency. We do not find any study showing effect of yoga on neurogenic inflammation. In summary, Integrated Yoga Therapy may have beneficial effect in reducing symptoms and improving quality of life for patients with allergic rhinitis. Yoga may reduce inflammation through mediating neuro-endocrino-immunological network. Future studies are needed to explore the mechanism how yoga might modulate immune inflammation cascade and neurogenic inflammation at the cellular level in relevance to allergic rhinitis; the effects of kriyas (yogic cleansing techniques) also need to be evaluated in early and late phase of AR. So the proposed model could guide future research.

Harmal Extract Induces Apoptosis of HCT116 Human Colon Cancer Cells, Mediated by Inhibition of Nuclear Factor-κB and Activator Protein-1 Signaling Pathways and Induction of Cytoprotective Genes

  • Elkady, Ayman I;Hussein, Rania A;El-Assouli, Sufian M
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.4
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    • pp.1947-1959
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    • 2016
  • Background: Colorectal cancer (CRC) is a major cause of morbidity and mortality, being the second most common type of cancer worldwide in both men and women. It accounts yearly for approximately 9% of all new cases of cancers. Furthermore, the current chemotherapeutic regimens seem unsatisfactory, so that exploration of novel therapeutic modalities is needed. The present study was undertaken to investigate the inhibitory effects of a crude alkaloid extract (CAERS) of a medicinal herb, Rhazya stricta, on proliferation of CRC HCT116 cells and to elucidate mechanisms of action. To achieve these aims, we utilized MTT, comet, DNA laddering and gene reporter assays, along with Western blot and RT-PCR analyses. Results: We found that CAERS inhibited cell proliferation and induced apoptotic cell death in HCT116 cells. Hallmarks of morphological and biochemical signs of apoptosis were clearly evident. CAERS down-regulated DNA-binding and transcriptional activities of NF-${\kappa}B$ and AP-1 proteins, while up-regulating expression of the Nrf-2 protein. It also down-regulated expression levels of the ERK MAPK, Bcl-2, cyclin D1, CDK-4, survivin and VEGF and up-regulated levels of Bax, caspase-3/7 and -9, p53, p21, Nrf-2. Markedly, it promoted mRNA expression levels of cytoprotective genes including the hemeoxygenase-1, NAD(P)H quinine oxidoreductase 1 and UDP-glucuronyltransferase. Conclusions: These findings indicate that CAERS exerts antiproliferative action on CRC cells through induction of apoptotic mechanisms, and suggest CAERS could be a promising agent for studying and developing novel chemotherapeutic agents aimed at novel molecular targets for the treatment of CRC.

A Novel Mutation in the DNA Binding Domain of NFKB is Associated with Speckled Leukoplakia

  • Govindarajan, Giri Valanthan Veda;Bhanumurthy, Lokesh;Balasubramanian, Anandh;Ramanathan, Arvind
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.7
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    • pp.3627-3629
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    • 2016
  • Background: Activation and inactivation of nuclear factor of kappa light chain gene enhancer in B cells (NFKB) is tightly regulated to ensure effective onset and cessation of defensive inflammatory signaling. However, mutations within NFKB, or change in activation and inactivation molecules have been reported in a few cancers. Although oral squamous cell carcinoma is one of the most prevalent forms of cancer in India, with a development associated with malignant transformation of precancerous lesions, the genetic status of NFKB and relative rates of change in oral precancerous lesions remain unknown. Hence in the present study we investigated all twenty four exons of NFKB gene in two precancerous lesions, namely oral submucous fibrosis (OSMF) and oral leukoplakia (OL) to understand its occurrence, incidence and assess its possible contribution to malignant transformation. Materials and Methods: Chromosomal DNA isolated from twenty five each of OSMF and OL tissue biopsy samples were subjected to PCR amplification with intronic primers flanking twenty four exons of the NFKB gene. The PCR amplicons were subsequently subjected to direct sequencing to elucidate the mutation status. Results: Sequence analysis identified a novel heterozygous mutation, c.419T>A causing substitution of leucine with glutamine at codon 140 (L140Q) in an OL sample. Conclusions: The identification of a substitution mutation L140Q within the DNA binding domain of NFKB in OL suggests that NFKB mutation may be relatively an early event during transformation. To the best of our knowledge, this study is the first to have identified a missense mutation in NFKB in OL.

Protective Mechanism of Hominis Placenta Extract Against ${H_2O_2}-Induced$ Apoptosis in $PGT-{\beta}$ Cells ($PGT-{\beta}$ 세포주에서 자하거 약침액의 $H_2O_2$로 인한 Apoptosis에 대한 방어 기전)

  • Jung-Chul, Seo;Jae-Dong, Lee;Dong-Suk, Park;Sung-Keel, Kang;Byung-Cheol, Ahn;Ee-Hwa, Kim;Soon-Ae, Kim;Hee-Jae, LeeK;Chang-Ju, Kim
    • The Journal of Korean Medicine
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    • v.22 no.3
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    • pp.92-97
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    • 2001
  • 목적 :본 연구는 최근 임상에서 많이 사용하는 자하거 약침액이 과산화수소($H_2O_2$)로 야기된 송과선 세포의 Apoptosis에 있어서 세포 보호에 미치는 영향과 그 기전을 분석하였다. 방법 :송과선 세포주에서 자하거 약침액의 $H_2O_2$로 인한 Apoptosis에 대한 방어 기전을 관찰하기 위하여 면역세포화학법. 세포화학법 및 reverse transcription-polymerase chain reaction (RT-PCR)을 시행하였다. 결과 : 자하거 약침액 투여군에서는 nuclear factor kappa B (NFkB), inducible nitric oxide synthase (iNOS), nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase의 발현이 $H_2O_2$ 투여군보다 감소하였다. RT-PCR에서는 caspase-3의 발현이 자하거 약침액 투여군에서 $H_2O_2$ 투여군보다 억제되었다. 결론: 이상의 결과를 통하여 자하거 약침액이 $H_2O_2$로 유발된 Apoptosis에서 세포보호 효과가 있으며 그 기전은 iNOS와 caspase-3의 억제에 기인할 가능성을 시사한다고 하겠다.

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Combined effect of bisphosphonate and recombinant human bone morphogenetic protein 2 on bone healing of rat calvarial defects

  • Kim, Ho-Chul;Song, Jae-Min;Kim, Chang-Joo;Yoon, Sang-Yong;Kim, In-Ryoung;Park, Bong-Soo;Shin, Sang-Hun
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.37
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    • pp.16.1-16.7
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    • 2015
  • Background: This study aimed to investigate new bone formation using recombinant human bone morphogenetic protein 2 (rhBMP-2) and locally applied bisphosphonate in rat calvarial defects. Methods: Thirty-six rats were studied. Two circular 5 mm diameter bony defect were formed in the calvaria using a trephine bur. The bony defect were grafted with $Bio-Oss^{(R)}$ only (group 1, n = 9), $Bio-Oss^{(R)}$ wetted with rhBMP-2 (group 2, n = 9), $Bio-Oss^{(R)}$ wetted with rhBMP-2 and 1 mM alendronate (group 3, n = 9) and $Bio-Oss^{(R)}$ wetted with rhBMP-2 and 10 mM alendronate (group 4, n = 9). In each group, three animals were euthanized at 2, 4 and 8 weeks after surgery, respectively. The specimens were then analyzed by histology, histomorphometry and immunohistochemistry analysis. Results: There were significant decrease of bone formation area (p < 0.05) between group 4 and group 2, 3. Group 3 showed increase of new bone formation compared to group 2. In immunohistochemistry, collagen type I and osteoprotegerin (OPG) didn't show any difference. However, receptor activator of nuclear factor ${\kappa}B$ ligand (RANKL) decreased with time dependent except group 4. Conclusion: Low concentration bisphosphonate and rhBMP-2 have synergic effect on bone regeneration and this is result from the decreased activity of RANKL of osteoblast.

Ethyl Docosahexaenoate and Its Acidic Form Increase Bone Formation by Induction of Osteoblast Differentiation and Inhibition of Osteoclastogenesis

  • Choi, Bo-Yun;Eun, Jae-Soon;Nepal, Manoj;Lee, Mi-Kyung;Bae, Tae-Sung;Kim, Byung-Il;Soh, Yun-Jo
    • Biomolecules & Therapeutics
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    • v.19 no.1
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    • pp.70-76
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    • 2011
  • Bone remodeling is a dynamic process involving a constant balance between osteoclast-induced bone resorption and osteoblast-induced bone formation. Osteoclasts play a crucial homeostatic role in skeletal modeling and remodeling, and destroy bone in many pathological conditions. Previously, we reported that the hexane soluble fraction of Ficus carica inhibited osteoclast differentiation. Poly unsaturated fatty acids, such as ethyl docosahexaenoate (E-DHA), docosahexaenoic acid (DHA), cis-11,14-eicosadienoic acid (EDA) and eicosapentaenoic acid (EPA), were identified from the hexane soluble fraction of Ficus carica. Among them, E-DHA most potently inhibited osteoclastogenesis in RAW264.7 cells. E-DHA reduced the activities of JNK and NF-$\kappa}B$. E-DHA suppressed the expression of c-Fos and nuclear factor of activated T cells c1 (NFATc1). Interestingly, DHA increased the activity of alkaline phosphatase and expression of bone morphogenetic protein 2 (BMP2) more than E-DHA in MC3T3-E1 cells, suggesting that DHA may induce osteoblast differentiation. The data suggests that a combination of E-DHA and DHA has potential use in the treatment of diseases involving abnormal bone lysis, such as osteoporosis, rheumatoid arthritis and periodontal bone erosion.

Anti-inflammatory Activities of Cheongpyehwadam-tang

  • Kwak Sang-Ho;Kim Ji-Young;Han Eun-Hee;Oh Kyo-Nyeo;Kim Dong-Hee;Jeong Hye-Gwang;Yoo Dong-Youl
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.19 no.5
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    • pp.1399-1404
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    • 2005
  • In oriental medicine, Cheongpyehwadam-tang (CHT) has long been used for the cure of inflammatory diseases in the lung and bronchus such as bronchitis, bronchial asthma, pneumonia and tuberculosis. It's use is currently further extended for the treatment of allergic asthma. To investigate the anti-inflammatory effects of CHT, we investigated the effects of CHT on the lipopolysaccharide (LPS)-induced nitric oxide (NO) and pro-inflammatory cytokines ($TNF-{\alpha}$, IL-6, and $IL-1{\beta}$) production, and on the level of inducible nitric oxide synthase (iNOS) and proinflammatory cytokines expression in murine macrophage RAW 264.7 cells. CHT alone did not affect NO or pro-inflammatory cytokines production. In contrast, CHT inhibited LPS-induced NO and proinflammatory cytokines and the levels of LPS-induced iNOS and proinflarnmatory cytokine mRNA in a dose-dependent manner. CHT also inhibited the nuclear factor-kappa B (NF-kB) activation. Taken together, these results suggested that CHT inhibits the production of NO and pro-inflammatory cytokines in RAW 264.7 cells through blockade of NF-kB activation.

Imperatorin Suppresses Degranulation and Eicosanoid Generation in Activated Bone Marrow-Derived Mast Cells

  • Jeong, Kyu-Tae;Lee, Eujin;Park, Na-Young;Kim, Sun-Gun;Park, Hyo-Hyun;Lee, Jiean;Lee, Youn Ju;Lee, Eunkyung
    • Biomolecules & Therapeutics
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    • v.23 no.5
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    • pp.421-427
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    • 2015
  • Imperatorin has been known to exert many biological functions including anti-inflammatory activity. In this study, we investigated the inhibitory effects of imperatorin on the production of inflammatory mediators in mouse bone marrow-derived mast cells (BMMC). Imperatorin inhibited degranulation and the generation of eicosanoids (leukotriene $C_4$ ($LTC_4$) and prostaglandin $D_2$ ($PGD_2$) in IgE/antigen (Ag)-stimulated BMMC. To elucidate the molecular mechanism involved in this process, we investigated the effect of imperatorin on intracellular signaling in BMMC. Biochemical analyses of the IgE/Ag-mediated signaling pathway demonstrated that imperatorin dramatically attenuated degranulation and the production of 5-lipoxygenase-dependent $LTC_4$ and cyclooxygenase-2-dependent $PGD_2$ through the inhibition of intracellular calcium influx/phospholipase $C{\gamma}1$, cytosolic phospholipase $A_2$/mitogen-activated protein kinases and/or nuclear factor-${\kappa}B$ pathways in BMMC. These results suggest that the effects of imperatorin on inhibition of degranulation and eicosanoid generation through the suppression of multiple steps of IgE/Ag-mediated signaling pathways would be beneficial for the prevention of allergic inflammation.

Anti-inflammatory Effect of the Processed Gardeniae Fructus in LPS-induced Macrophages (LPS로 유도된 대식세포에서 수치 치자의 항염효과)

  • An, Iseul;Kim, Sang Chan;Byun, Sung Hui;Lee, Jong Rok;Park, Sook Jahr
    • Herbal Formula Science
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    • v.27 no.4
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    • pp.245-255
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    • 2019
  • Objective : Herbal processing is one of the traditional techniques used in Korean medicine to increase the effectiveness of herbs or reduce their toxicity. In this study, Gardeniae Fructus processed with ginger juice and alcohol was prepared to evaluate the anti-inflammatory effect on lipopolysaccharide (LPS)-induced macrophages. Methods : The processing of Gardeniae Fructus was performed by adding 40 % ginger juice or 10% alcohol to the total weight of Gardeniae Fructus and then roasting at 150℃ for 5 minutes. Cell viability was determined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. To detect nitric oxide (NO) production, culture media were mixed with Griess reagent and measured the absorbance at 540 nm. Prostaglandin E2 (PGE2) and pro-inflammatory cytokines were detected by enzyme-linked immunosorbent assay (ELISA). Western blot was applied to monitor protein expression levels. Results : LPS-induced NO, PGE2 and inflammatory cytokines were decreased by the treatment of normal or processed Gardeniae Fructus ethanol extracts (GFE). Compared to normal GFE, the processed GFE showed a stronger inhibitory effect on the production of NO and PGE2. These inhibitory effect of GFE was due to the suppression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) mediated from the inhibition of nuclear factor kappa B (NF-κB). Furthermore, processed GFE showed more suppressive effects on the expression of iNOS, COX-2 and IκBα proteins than normal GFE. Conclusion : From these results, it was concluded that GFE had an improved anti-inflammatory effect compared to normal GFE. These results provide an objective evidences for the use of herbal processing in Korean medicine.

Anti-inflammatory Effects of 8α-hydroxy pinoresinol isolated from Nardostachys jatamansi on Lipopolysaccharide-induced Inflammatory Response in RAW 264.7 Cells. (LPS로 유도된 RAW 264.7 세포의 염증반응에서 감송향(甘松香)에서 추출한 8α-hydroxy pinoresinol의 항염증 효과)

  • Choi, Sun Bok;Park, Sung-Joo
    • The Korea Journal of Herbology
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    • v.31 no.5
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    • pp.1-6
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    • 2016
  • Objectives : Nardostachys jatamansi (NJ) is a medicinal herb that has been reported in various traditional systems of medicine for its use in antispasmodic, a digestive stimulant, skin diseases. Previous studies have already reported that NJ effectively protects against inflammation. However, the active compound in NJ is unknown. Therefore, in the present study, we analyzed effects of a compound, 8α-hydroxy pinoresinol (HP), isolated from NJ against lipopolysaccharide (LPS) induced inflammation in RAW 264.7 cells.Methods : To examine the anti-inflammatory effect of HP against LPS, intraperitoneally pre-treat the HP (100, 200, 500 and 1,000 nM) 1 h prior to LPS challenges. LPS was stimulated with 500 ng/ml in RAW 264.7 cells. To identify the anti-inflammatory effect of HP, we measured inflammatory mediators such as inducible nitric oxide synthase (iNOS) and its derivative nitric oxide (NO), cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2). Also we evaluated molecular mechanisms including mitogen-activated protein kinases (MAPKs) and nuclear factor-kappaB (NF-κB) activation by western blot.Results : The HP inhibited production of inflammatory mediators, such as iNOS and its derivative NO, COX-2 and PGE2 in LPS- induced inflammationin RAW 264.7 cells. Additionally, HP also inhibited activation of p38 pathway signaling but not extracellularsignal-regulatedkinase (ERK), c-jun NH2-terminal kinase (JNK), and NF-κB.Conclusion : Our results suggest that HP has anti-inflammatory functions through the dephosphorylation of p38 and HP can provide beneficial strategy for prevention and therapy of inflammation.