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Journal ArticleDOI

Inhibition of Lipopolysaccharide-Stimulated Neuro- Inflammatory Kuntze in BV-2 Microglial Cell Mediators by Tetragonia tetragonoides (Pall)

13 Jan 2015-Tropical Journal of Pharmaceutical Research (Faculty of Pharmacy, University of Benin)-Vol. 13, Iss: 12, pp 2005-2010

TL;DR: The results suggest that TKE can be explored as a potential therapeutic agent for regulating microglia-mediated neuroinflammatory responses observed in several neurodegenerative diseases.

AbstractPurpose: To investigate the in vitro antioxidant and anti-neuroinflammatory effects of Tetragonia tetragonoides (Pall.) Kuntze extract (TKE) in lipopolysaccharide (LPS)-stimulated BV-2 microglial cells. Methods: To evaluate the effects of TKE, LPS-stimulated BV microglia were used and the expression and production of inflammatory mediators, namely, nitric oxide (NO), inducible NO synthase (iNOS) and tumor necrosis alpha (TNF-α) were evaluated. Antioxidant activity of TKE was measured using 1, 1diphenyl-2-picryl-hydrazyl (DPPH) assay. Cell viabilities were estimated by 3-(4, 5-dimethylthiazol-2-yl)2, 5- diphenyl-tetrazolium bromide (MTT) assay. Results: TKE significantly suppressed LPS-induced production of NO (p < 0.001 at 20, 40, 80 and 100 μg/ml) and expression of iNOS in BV-2 cells. TKE also suppressed LPS-induced increase in TNF-α level (p < 0.001at 100 μg/ml) in BV-2 cells. In addition, DPPH-generated free radicals were inhibited by TKE in a concentration-dependent manner. Conclusion: The results suggest that TKE can be explored as a potential therapeutic agent for regulating microglia-mediated neuroinflammatory responses observed in several neurodegenerative diseases.

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Journal ArticleDOI
09 Nov 2000-Nature
TL;DR: Evidence that the appropriate and inappropriate production of oxidants, together with the ability of organisms to respond to oxidative stress, is intricately connected to ageing and life span is reviewed.
Abstract: Living in an oxygenated environment has required the evolution of effective cellular strategies to detect and detoxify metabolites of molecular oxygen known as reactive oxygen species. Here we review evidence that the appropriate and inappropriate production of oxidants, together with the ability of organisms to respond to oxidative stress, is intricately connected to ageing and life span.

8,016 citations


"Inhibition of Lipopolysaccharide-St..." refers methods in this paper

  • ...It is well known that DPPH radical assay is one of the widely used methods for evaluating the free radical scavenging activities of several antioxidants [12]....

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Journal ArticleDOI
TL;DR: Reporter constructs containing truncated promoter regions revealed that activation of NF-kappa B/Rel is critical in the induction of iNOS by LPS, however, additional, newly synthesized proteins contribute to the NF- kappa Bd-dependent transcription factor complex on the iN OS promoter in LPS-treated mouse macrophages.
Abstract: The promoter of the murine gene encoding inducible nitric oxide synthase (iNOS) contains an NF-kappa B site beginning 55 base pairs upstream of the TATA box, designated NF-kappa Bd Reporter constructs containing truncated promoter regions, when transfected into macrophages, revealed that NF-kappa Bd is necessary to confer inducibility by bacterial lipopolysaccharide (LPS) Oligonucleotide probes containing NF-kappa Bd plus the downstream 9 or 47 base pairs bound proteins that rapidly appeared in the nuclei of LPS-treated macrophages The nuclear proteins bound to both probes in an NF-kappa Bd-dependent manner, but binding was resistant to cycloheximide only for the shorter probe The proteins binding both probes reacted with antibodies against p50 and c-rel but not RelB; those binding the shorter probe also reacted with anti-RelA (p65) Pyrrolidine dithiocarbamate, which acts as a specific inhibitor of NF-kappa B, blocked both the activation of the NF-kappa Bd-binding proteins and the production of NO in LPS-treated macrophages Thus, activation of NF-kappa B/Rel is critical in the induction of iNOS by LPS However, additional, newly synthesized proteins contribute to the NF-kappa Bd-dependent transcription factor complex on the iNOS promoter in LPS-treated mouse macrophages

2,166 citations


"Inhibition of Lipopolysaccharide-St..." refers background in this paper

  • ...Mounting evidence indicate that microbial endotoxins like LPS can directly activate microglia triggering the production of proinflammatory mediators, such as nitric oxide (NO), inducible NO synthase (iNOS), interleukins (IL) and tumor necrosis factor (TNF)-α [6-8]....

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  • ...Studies have shown that anti-oxidant and anti-inflammatory agents may inhibit microglial activation and thus protect against neuronal cell death seen in various neurodegenerative disorders [7,8]....

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Journal ArticleDOI
TL;DR: Recent advances on the study of the role of microglia based on findings from animal and cell culture models in the pathogenesis of neurodegenerative diseases, with particular emphasis on Parkinson's disease are summarized.
Abstract: Evidence from postmortem analysis implicates the involvement of microglia in the neurodegenerative process of several degenerative neurological diseases, including Alzheimer's disease and Parkinson's disease. It remains to be determined, however, whether microglial activation plays a role in the initiation stage of disease progression or occurs merely as a response to neuronal death. Activated microglia secrete a variety of proinflammatory and neurotoxic factors that are believed to induce and/or exacerbate neurodegeneration. In this article, we summarize recent advances on the study of the role of microglia based on findings from animal and cell culture models in the pathogenesis of neurodegenerative diseases, with particular emphasis on Parkinson's disease. In addition, we also discuss novel approaches to potential therapeutic strategies.

1,013 citations


"Inhibition of Lipopolysaccharide-St..." refers background in this paper

  • ...Mounting evidence indicate that microbial endotoxins like LPS can directly activate microglia triggering the production of proinflammatory mediators, such as nitric oxide (NO), inducible NO synthase (iNOS), interleukins (IL) and tumor necrosis factor (TNF)-α [6-8]....

    [...]


Journal ArticleDOI
TL;DR: It is suggested that the galloyl moiety attached to flavan-3-ol at 3 position has a strong scavenging ability on the DPPH radical as well as the ortho-trihydroxyl group in the B ring, which elevates the radical scavenging efficiency above that of the orthosylated group; as has been recognized in other flavonoids such as flavones.
Abstract: The scavenging effects of tea catechins and their epimerized, acylated, and glucostylated derivatives on 1,1-diphenyl-2-picrythydrazyl (DPPH) radical were evaluated by electron spin resonance spectrometry. Tea catechins and their epimers were shown to have 50% radical scavenging ability in the concentration range of 1 to 3 microM. No significant differences were observed between the scavenging activities of tea catechins and their epimers, and, hence, the scavenging effects of catechins are not dependent on their sterical structure. The relationship between scavenging ability and the structure of tea catechins was also examined with acylated and glucosylated catechin derivatives. It is suggested that the galloyl moiety attached to flavan-3-ol at 3 position has a strong scavenging ability on the DPPH radical as well as the ortho-trihydroxyl group in the B ring, which elevates the radical scavenging efficiency above that of the ortho-dihydroxyl group; as has been recognized in other flavonoids such as flavones. The results obtained from the reactivity of tea catechins with the DPPH radical at different pHs suggest not only that the ortho-trihydroxyl group and the galloyl moiety contribute to maintaining the DPPH radical scavenging ability more effectively in a wide range of conditions from acidic to alkaline, but also that the radical scavenging efficiency of the ortho-dihydroxyls in the B ring is limited in neutral to alkaline regions. The difference between the scavenging abilities of the trihydroxyls (probably in the galloyl moiety) and the dihydroxyls can be explained in terms of redox potentials. It is concluded that the ortho-trihydroxyl group in the B ring and the galloyl moiety at 3 position of flavan-3-ol skeleton are the most important structural features for displaying an excellent scavenging ability on the DPPH radical.

746 citations


"Inhibition of Lipopolysaccharide-St..." refers methods in this paper

  • ...The amount of stable nitrite, the end product of NO generation by activated microglia was determined by a colorimetric assay as previously described [10]....

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  • ...Cell viability was determined by 3-(4, 5-dimethylthiazol-2-yl)-2,5diphenyltetrazolium bromide (MTT) assay as described previously [10]....

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Journal ArticleDOI
TL;DR: The possible functions of resident and recruited macrophages in the developing and adult nervous system are reviewed and what contribution these cells might make to repair mechanisms in the central and peripheral nervous systems are examined.
Abstract: Why might macrophages be of interest to neurobiologists? Recent evidence shows that macrophages play a role in tissue homeostasis as well as in defence and repair of tissues. We will review here the possible functions of resident and recruited macrophages in the developing and adult nervous system and examine what contribution these cells might make to repair mechanisms in the central and peripheral nervous systems. There is increasing evidence that macrophages form an important component of the non-neuronal cell population in the nervous system and the tools are becoming available that allow us to study these cells in situ.

741 citations


"Inhibition of Lipopolysaccharide-St..." refers background in this paper

  • ...Trop J Pharm Res, December 2014; 13(12): 2006 processes can attenuate the severity of neurodegeneration [5]....

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