Inhibition of nitric oxide by phenylethanoids in activated macrophages

Xiong, Quanbo; Tezuka, Yasuhiro; Kaneko, T.; Li, Huiying; Tran, Le Quan; Hase, Koji; Namba, Tsuneo; Kadota, Shigetoshi

doi:10.1016/s0014-2999(00)00354-x

Cited by 93 publications

(64 citation statements)

References 29 publications

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“…Induction of iNOS and downstream NO production have multiple roles, not only in fighting infectious disease but also in a range of autoimmune and inflammatory diseases (54)(55)(56)(57)(58). In the case of chronic infections, a potential therapeutic strategy to prolong iNOS expression and increase NO production could be to disrupt the SPSB-iNOS interaction.…”

Section: Discussionmentioning

confidence: 99%

TLR Regulation of SPSB1 Controls Inducible Nitric Oxide Synthase Induction

Lewis

Kolesnik

Kuang

et al. 2011

The Journal of Immunology

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The mammalian innate immune system has evolved to recognize foreign molecules derived from pathogens via the TLRs. TLR3 and TLR4 can signal via the TIR domain-containing adapter inducing IFN-β (TRIF), which results in the transcription of a small array of genes, including IFN-β. Inducible NO synthase (iNOS), which catalyzes the production of NO, is induced by a range of stimuli, including cytokines and microbes. NO is a potent source of reactive nitrogen species that play an important role in killing intracellular pathogens and forms a crucial component of host defense. We have recently identified iNOS as a target of the mammalian SPSB2 protein. The SOCS box is a peptide motif, which, in conjunction with elongins B and C, recruits cullin-5 and Rbx-2 to form an active E3 ubiquitin ligase complex. In this study, we show that SPSB1 is the only SPSB family member to be regulated by the same TLR pathways that induce iNOS expression and characterize the interaction between SPSB1 and iNOS. Through the use of SPSB1 transgenic mouse macrophages and short hairpin RNA knockdown of SPSB1, we show that SPSB1 controls both the induction of iNOS and the subsequent production of NO downstream of TLR3 and TLR4. Further, we demonstrate that regulation of iNOS by SPSB1 is dependent on the proteasome. These results suggest that SPSB1 acts through a negative-feedback loop that, together with SPSB2, controls the extent of iNOS induction and NO production.

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Section: Discussionmentioning

confidence: 99%

TLR Regulation of SPSB1 Controls Inducible Nitric Oxide Synthase Induction

Lewis

Kolesnik

Kuang

et al. 2011

The Journal of Immunology

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“…Seven PhGs from the stems of Cistanche deserticola were found to reduce or inhibit nitrite accumulation in LPS-stimulated J774.1 cells or mouse peritoneal exudate macrophages [220]. It has been suggested that the anti-inflammatory effects of the tested PhGs may be due to their nitrite radical-scavenging activity.…”

Section: Anti-inflammatory and Immunomodulating Activitiesmentioning

confidence: 99%

Naturally Occurring Phenylethanoid Glycosides: Potential Leads for New Therapeutics

Fu¹,

Pang²,

Wong

2008

CMC

134

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ABATRACTNatural products have long been regarded as excellent sources for drug discovery given their structure diversity and wide variety of biological activities. Phenylethanoid glycosides are naturally occurring compounds of plant origin and are structurally characterized with a hydroxyphenylethyl moiety to which a glucopyranose is linked through a glycosidic bond. To date several hundred compounds of this type have been isolated from medicinal plants and further pharmacological studies in vitro or in vivo have shown that these compounds possess a broad array of biological activities including antibacterial, antitumor, antiviral, anti-inflammatory, neuro-protective, antioxidant, hepatoprotective, immunomodulatory, and tyrosinase inhibitory actions. Given their extensive activity profile, structure-activity relationships analyses of these compounds have been performed in a number of studies to reveal potential leads for future drug design. This article will summarize the major developments in phenylethanoid glycosides-based research in the past decade. The progresses made in phytochemistry and biological activity studies of these compounds will be reviewed. Particular attention will be given to the novel structures identified to date and the prominent therapeutic values associated with these molecules.

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“…ECH is also the main phenolic component in Echinacea angustifolia and Echinacea pallida roots (Perry et al, 2001), which are widely used in Europe, North America, and Australia for their immunostimulating activities. As a natural polyphenolic compound, ECH showed various bioactivities, such as antioxidative (Li et al, 1992;Xiong et al, 1996;Hu and Kitts, 2000;Cervellati et al, 2002), neuroprotective (Den et al, 2004;Koo et al, 2005;Chen et al, 2007;Geng et al, 2007), nitric oxide radical-scavenging (Xiong et al, 2000), and antihepatotoxic activities (Houghton and Hikino, 1989;Wu et al, 2007).…”

mentioning

confidence: 99%

Metabolism of Echinacoside, a Good Antioxidant, in Rats: Isolation and Identification of Its Biliary Metabolites

Jia

H²,

Jin³

et al. 2008

Drug Metab Dispos

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, 1997), which is an important traditional Chinese medicine used for the treatment of kidney deficiency and neurodegenerative diseases. ECH is also the main phenolic component in Echinacea angustifolia and Echinacea pallida roots (Perry et al., 2001), which are widely used in Europe, North America, and Australia for their immunostimulating activities. As a natural polyphenolic compound, ECH showed various bioactivities, such as antioxidative (Li et al., 1992;Xiong et al., 1996;Hu and Kitts, 2000;Cervellati et al., 2002), neuroprotective (Den et al., 2004;Koo et al., 2005;Chen et al., 2007;Geng et al., 2007), nitric oxide radical-scavenging (Xiong et al., 2000), and antihepatotoxic activities (Houghton and Hikino, 1989;Wu et al., 2007).Although ECH exhibited diverse bioactivities in in vivo and in vitro assays, only a few reports dealing with the metabolism and disposition of ECH are available. In our previous study on the pharmacokinetics and bioavailability of ECH in rat, the distribution and elimination of ECH were extremely fast (t 1/2␣ , 12.4 min; t 1/2␤ , 41.0 min), clearance was 0.0001 mg/kg/min/(ng/ml) after i.v. administration (5 mg/kg), and the bioavailability of ECH was only 0.83% (Jia et al., 2006). The very low bioavailability of ECH was consistent with the results of Matthias et al. (2004), in which ECH permeated poorly through the Caco-2 monolayers. Moreover, our pharmacokinetic data suggested that ECH was mostly metabolized after dosing. Therefore, we hypothesized that, in addition to the parent compound, some metabolic products of ECH may show biological activities, thereby contributing to the pharmacological efficacy of ECH in vivo. It was necessary to

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Inhibition of nitric oxide by phenylethanoids in activated macrophages

Cited by 93 publications

References 29 publications

TLR Regulation of SPSB1 Controls Inducible Nitric Oxide Synthase Induction

TLR Regulation of SPSB1 Controls Inducible Nitric Oxide Synthase Induction

Naturally Occurring Phenylethanoid Glycosides: Potential Leads for New Therapeutics

Metabolism of Echinacoside, a Good Antioxidant, in Rats: Isolation and Identification of Its Biliary Metabolites

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