scholarly journals Andrographolide Activates Keap1/Nrf2/ARE/HO-1 Pathway in HT22 Cells and Suppresses Microglial Activation by Aβ42through Nrf2-Related Inflammatory Response

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Ji Yeon Seo ◽  
Euisun Pyo ◽  
Jin-Pyo An ◽  
Jinwoong Kim ◽  
Sang Hyun Sung ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Microglial Activation ◽  
Cell Activation ◽  
Inflammatory Responses ◽  
Antioxidant Response ◽  
Nuclear Factor ◽  
Antioxidant Response Element ◽  
Ht22 Cells ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Therapeutic approach of Alzheimer’s disease (AD) has been gradually diversified. We examined the therapeutic and preventive potential of andrographolide, which is a lactone diterpenoid fromAndrographis paniculata, and focused on the Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-mediated heme oxygenase (HO)-1-inducing effects and the inhibitory activity of amyloid beta (Aβ)42-induced microglial activation related to Nrf2 and nuclear factorκB (NF-κB)-mediated inflammatory responses. Andrographolide induced the expression and translocation of Nrf2 from the cytoplasm to the nucleus, thereby activating antioxidant response element (ARE) gene transcription and HO-1 expression in murine hippocampal HT22 cells. Andrographolide eliminated intracellular Aβ42in BV-2 cells and decreased the production of interleukin (IL)-6, IL-1β, prostaglandin (PG)E2, and nitric oxide (NO) because of artificial phagocytic Aβ42. It decreased pNF-κB accumulation in the nucleus and the expression of inducible nitric oxide synthase (i-NOS) and cyclooxygenase II (COX-II) in the microglial BV-2 cell line. In summary, andrographolide activates Nrf2-mediated HO-1 expression and inhibits Aβ42-overexpressed microglial BV-2 cell activation. These results suggested that andrographolide might have the potential for further examination of the therapeutics of AD.

scholarly journals Activation of Nuclear Factor κB and Induction of Inducible Nitric Oxide Synthase by Ureaplasma urealyticumin Macrophages

2000 ◽  
Vol 68 (12) ◽  
pp. 7087-7093 ◽  
Author(s):  
Y.-H. Li ◽  
Z.-Q. Yan ◽  
J. Skov Jensen ◽  
K. Tullus ◽  
A. Brauner
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Alveolar Macrophages ◽  
Nuclear Factor Κb ◽  
Inos Expression ◽  
Dependent Manner ◽  
Nuclear Factor ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

ABSTRACT Chronic lung disease (CLD) of prematurity is an inflammatory disease with a multifactorial etiology. The importance ofUreaplasma urealyticum in the development of CLD is debated, and steroids produce some improvement in neonates with this disease. In the present study, the capability of U. urealyticum to stimulate rat alveolar macrophages to produce nitric oxide (NO), express inducible nitric oxide synthase (iNOS), and activate nuclear factor κB (NF-κB) in vitro was characterized. The effect of NO on the growth of U. urealyticum was also investigated. In addition, the impact of dexamethasone and budesonide on these processes was examined. We found that U. urealyticum antigen (≥4 × 107 color-changing units/ml) stimulated alveolar macrophages to produce NO in a dose- and time-dependent manner (P < 0.05). This effect was further enhanced by gamma interferon (100 IU/ml; P < 0.05) but was attenuated by budesonide and dexamethasone (10−4 to 10−6 M) (P < 0.05). The mRNA and protein levels of iNOS were also induced in response to U. urealyticum and inhibited by steroids.U. urealyticum antigen triggered NF-κB activation, a possible mechanism for the induced iNOS expression, which also was inhibited by steroids. NO induced by U. urealyticum caused a sixfold reduction of its own growth after infection for 10 h. Our findings imply that U. urealyticum may be an important factor in the development of CLD. The host defense response againstU. urealyticum infection may also be influenced by NO. The down-regulatory effect of steroids on NF-κB activation, iNOS expression, and NO production might partly explain the beneficial effect of steroids in neonates with CLD.

scholarly journals Isolation and characterization of cytotoxic and anti-inflammatory constituents from Scoparia dulcis L

2020 ◽  
Vol 44 (7-8) ◽  
pp. 381-387
Author(s):  
Mohammad Nur-e-Alam ◽  
Sarfaraz Ahmed ◽  
Muhammad Yousaf ◽  
Shabana I Khan ◽  
Ramzi A Mothana ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Acetic Acid ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Nuclear Factor Kappa B ◽  
Nuclear Factor ◽  
Scoparia Dulcis ◽  
Anti Inflammatory ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Scoparia dulcis L. is one of the edible widely distributed Scropholariaceae species in Asia, Africa and America. It is used in the treatment of respiratory and inflammatory diseases, diabetes, hypertension, cancer, hepatitis and tuberculosis. A phytochemical investigation on S. dulcis led to the isolation of two new acyclic diterpenes Acetic acid 6-hydroxy-2-(6-hydroxy-4-methyl-hex-4-enylidene)-4,8-dimethyl-undeca-4,8-dienyl ester (1) and Acetic acid 8-hydroxy-2-(6-hydroxy-4-methyl-hex-4-enylidene)-6,10-dimethyl-undeca-5,9-dienyl ester (2) in addition to eight known compounds (3–10), namely scopadulciol (3), 4- epi-scopadulcic acid B (4), dulcidiol (5), scopadulcic acid B (6), hymenoxin (7), glutinol (8), eupatilin (9) and 5-demethylnobiletin (10). The structures elucidation was performed using spectroscopic means, including 1D and 2D nuclear magnetic resonance and high-resolution electrospray ionization mass spectrum spectrometric analysis. Furthermore, the isolated compounds were investigated for their anti-inflammatory activity through the determination of inhibition of nuclear factor-kappa B activity in human chondrosarcoma (SW1353) cells, the inhibition of inducible nitric oxide synthase mouse macrophages (RAW264.7) and the decrease in cellular oxidative stress in HepG2 cells. Moreover, the cytotoxic activity was investigated against four cancer and two kidney cell lines. Among the isolates, 3, 5 and 10 showed anti-inflammatory activity in terms of inhibiting nuclear factor-kappa B and inducible nitric oxide synthase. Compounds 3–5 were the most cytotoxic towards cancer cell lines (IC50: 3.8 µM to 42.3 µM) followed by 10 (IC50: 30.9- > 64.4 µM). Cytotoxicity of compounds 3–5 was comparable to the activity of doxorubicin.

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