Inhibition of iNOS gene expression by quercetin is mediated by the inhibition of IκB kinase, nuclear factor-kappa B and STAT1, and depends on heme oxygenase-1 induction in mouse BV-2 microglia

Chen, Jui-Ching; Ho, Feng-Ming; Chao, Pei‐Dawn Lee; Chen, Chih‐Ping; Jeng, Kee-Ching; Hsu, Hsiu-Bao; Lee, Sho-Tone; Wu, Wen Tung; Lin, Wan-Wan

doi:10.1016/j.ejphar.2005.08.005

Cited by 242 publications

(171 citation statements)

References 51 publications

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“…However, it is unclear whether activation of adenosine receptors is required for adenosine-mediated HO-1 expression. Previously, we and others reported that HO-1 is a strong antioxidant/anti-inflammatory enzyme that reduces intracellular ROS production and proinflammatory mediators in microglia (Chen et al, 2005;Min et al, 2006). Therefore, adenosine-induced HO-1 production may contribute to the anti-inflammatory effect of adenosine in microglia.…”

Section: Discussionmentioning

confidence: 82%

Adenosine induces hemeoxygenase‐1 expression in microglia through the activation of phosphatidylinositol 3‐kinase and nuclear factor E2‐related factor 2

Min

Kim

Jou

et al. 2008

Glia

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Adenosine, a purine nucleoside, has been reported to suppress the inflammatory responses of microglia in the brain. However, the underlying mechanisms of its anti-inflammatory action are unclear at present. Here we show that adenosine reduces the increase in intracellular reactive oxygen species (ROS) through expression of an antioxidant enzyme, hemeoxygenase-1 (HO-1). The H 2 O 2 -induced intracellular ROS level was significantly low in microglia pretreated with adenosine for 3-6 h, compared with that in untreated cells. Adenosine induced HO-1 mRNA and protein expression within 3 h, which was maintained for up to 12 h. Nuclear factor E2-related factor 2 (Nrf2), a transcription factor, and phosphatidylinositol 3-kinase (PI3K) and Akt pathways appear to mediate HO-1 expression. In response to adenosine, Nrf2 translocated from the cytosol to nuclei, and bound to the antioxidant response element (ARE). Adenosine enhanced HO-1 promoter activity in an ARE-dependent manner. Moreover, the nucleoside stimulated Akt phosphorylation, and suppressors of PI3K (LY294002 and wortmannin) reduced adenosine-induced HO-1 expression. However, we propose that the effects of adenosine are independent of adenosine receptors, since agonists and antagonists of A1, A2a, and A3 had little effect on the regulation of intracellular ROS and HO-1 expression. Our results collectively suggest that adenosine acts as an endogenous regulator of brain inflammation via modulation of microglial ROS production. V

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Section: Discussionmentioning

confidence: 82%

Adenosine induces hemeoxygenase‐1 expression in microglia through the activation of phosphatidylinositol 3‐kinase and nuclear factor E2‐related factor 2

Min

Kim

Jou

et al. 2008

Glia

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“…Earlier studies have shown that the anti-inflammatory action of flavonoids is mediated via their inhibition of iNOS protein and mRNA expression as well as their inhibition of nuclear factor kB (NF-kB) and STAT-1 activation, which are involved in the expression of several inflammatory genes (Chen et al 2005;Hämäläinen et al 1999).…”

Section: Resultsmentioning

confidence: 99%

Potential anti-inflammatory, anti-adhesive, anti/estrogenic, and angiotensin-converting enzyme inhibitory activities of anthocyanins and their gut metabolites

et al. 2012

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Epidemiological studies have indicated a positive association between the intake of foods rich in anthocyanins and the protection against cardiovascular diseases. Some authors have shown that anthocyanins are degraded by the gut microflora giving rise to the formation of other breakdown metabolites, which could also contribute to anthocyanin health effects. The objective of this study was to evaluate the effects of anthocyanins and their breakdown metabolites, protocatechuic, syringic, gallic, and vanillic acids, on different parameters involved in atherosclerosis, including inflammation, cell adhesion, chemotaxis, endothelial function, estrogenic/anti-estrogenic activity, and angiotensin-converting enzyme (ACE) inhibitory activity. From the assayed metabolites, only protocatechuic acid exhibited a slight inhibitory effect on NO production and TNF-a secretion in LPS-INF-c-induced macrophages. Gallic acid caused a decrease in the secretion of MCP-1, ICAM-1, and VCAM-1 in endothelial cells. All anthocyanins showed an ACE-inhibitory activity. Delphinidin-3-glucoside, pelargonidin-3-glucoside, and gallic acid showed affinity for ERb and pelargonidin and peonidin-3-glucosides for ERa. The current data suggest that anthocyanins and their breakdown metabolites may partly provide a protective effect against atherosclerosis that is multi-causal and involves different biochemical pathways. However, the concentrations of anthocyanins and their metabolites, as used in the present cell culture and in vitro assays mediating anti-inflammatory, anti-adhesive, antiestrogenic, and angiotensin-converting enzyme inhibitory activities, were often manifold higher than those physiologically achievable.

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“…In the classical or canonical pathway, the phosphorylation by IkappaB kinase (IKK) of two specific serines near the N-terminus of IkB-alpha targets this protein for ubiquitination and degradation by the 26S proteasome. It has been demonstrated that flavonoids inhibit the phosphorylation of IkB by IKK [74][75][76]. We hypothesized that this inhibition could be the consequence of the binding of flavonoids to the phosphorylation site of IkB-alpha.…”

Section: Resultsmentioning

confidence: 99%

Pomegranate (Punica granatum): a natural source for the development of therapeutic compositions of food supplements with anticancer activities based on electron acceptor molecular characteristics

Nicolson¹,

Veljković²,

Glišić³

et al. 2016

FFHD

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Citation: Veljkovic V.V., Glisic S., Perovic V., Veljkovic N., Nicolson G.L.. Pomegranate (Punica granatum): a natural source for the development of therapeutic compositions of food supplements with anticancer activities based on electron acceptor molecular characteristics. Health and Disease 2016; 6(12):769-787 ABSTRACT Background: Numerous in vitro and in vivo studies, in addition to clinical data, demonstrate that pomegranate juice can prevent or slow-down the progression of some types of cancers. Despite the well-documented effect of pomegranate ingredients on neoplastic changes, the molecular mechanism(s) underlying this phenomenon remains elusive. Functional Foods in Methods:For the study of pomegranate ingredients the electron-ion interaction potential (EIIP) and the average quasi valence number (AQVN) were used. These molecular descriptors can be used to describe the long-range intermolecular interactions in biological systems and can identify substances with strong electron-acceptor properties. In this study, candidate human proteins interacting with pomegranate flavonoids have been analyzed by the informational spectrum method (ISM). This represents a virtual spectroscopy method for studying protein molecular interactions.Results: Our analysis indicates that the anti-cancer properties of pomegranate juice can be ascribed to the strong electron-acceptor properties of its chemical ingredients. This analysis also suggests that pomegranate flavonoids inhibit the "NF-kappaB" (NF-κB) pathway, which plays a critical role in the pathogenesis of cancer. Conclusion:The results offer a possible explanation for an important molecular mechanism underlying the anticancer activity of pomegranate ingredients, which could also serve as a basis for the development of new therapeutic compositions of food supplements with pomegranatelike anticancer properties.Key words: cancer, pomegranate, flavonoids, food supplement, informational spectrum method BACKGROUND With more than 10 million new cases world-wide reported each year, cancer is one of the most devastating human diseases [1]. Despite progress in the understanding and treatment of these diseases including significant improvements in diagnostics and therapy based on applications of modern technology, the incidence and cure rates of various cancers, even in highly developed countries, have not improved significantly [2]. For this reason, increased attention has turned to complementary therapies, including natural dietary supplements. Among these natural agents, pomegranate (Punica granatum) juice has drawn a great deal of attention from both the scientific community and the general public due to its demonstrated ability to suppress cancers [3][4][5][6][7][8][9][10][11][12][13]. For example, pomegranate has been found to possess well-documented cancer chemopreventive and chemotherapeutic effects against prostate cancer [10][11][12][13]. The results of a Phase II clinical study of patients with rising prostate-specific antigen (PSA) levels following surgery or radiation ...

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Inhibition of iNOS gene expression by quercetin is mediated by the inhibition of IκB kinase, nuclear factor-kappa B and STAT1, and depends on heme oxygenase-1 induction in mouse BV-2 microglia

Cited by 242 publications

References 51 publications

Adenosine induces hemeoxygenase‐1 expression in microglia through the activation of phosphatidylinositol 3‐kinase and nuclear factor E2‐related factor 2

Adenosine induces hemeoxygenase‐1 expression in microglia through the activation of phosphatidylinositol 3‐kinase and nuclear factor E2‐related factor 2

Potential anti-inflammatory, anti-adhesive, anti/estrogenic, and angiotensin-converting enzyme inhibitory activities of anthocyanins and their gut metabolites

Pomegranate (Punica granatum): a natural source for the development of therapeutic compositions of food supplements with anticancer activities based on electron acceptor molecular characteristics

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