Inhibition by Magnolol of Formylmethionyl-leucyl-phenyl alanine-induced Respiratory Burst in Rat Neutrophils

Wang, J P; Hsu, Mei‐Feng; Raung, Shue L; Chang, Ling‐Chu; Tsao, Lo T; Lin, Pei-Yu; Chen, C C

doi:10.1211/0022357991772466

Cited by 29 publications

(21 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition to the compounds described earlier, other plant-derived natural products-many that have been used as traditional medicines-have been reported to inhibit NOX enzymes (122). These include Honokio (269,307), Norathyriol (104), Abruquinone A (103), Magnolol (113,319), and Prodigiosin (193,208). However, little is known about their chemical or biochemical mechanisms of action, and some (e.g., Norathyriol, Abruquinone A, Magnolol) appear to target signaling pathways that lie upstream of NOX enzymes.…”

Section: Other Reported Nox Inhibitorsmentioning

confidence: 96%

NOX2 As a Target for Drug Development: Indications, Possible Complications, and Progress

Diebold

Smith

Yang

et al. 2015

Antioxidants & Redox Signaling

106

View full text Add to dashboard Cite

Significance: NOX2 is important for host defense, and yet is implicated in a large number of diseases in which inflammation plays a role in pathogenesis. These include acute and chronic lung inflammatory diseases, stroke, traumatic brain injury, and neurodegenerative diseases, including Alzheimer's and Parkinson's Diseases. Recent Advances: Recent drug development programs have targeted several NOX isoforms that are implicated in a variety of diseases. The focus has been primarily on NOX4 and NOX1 rather than on NOX2, due, in part, to concerns about possible immunosuppressive side effects. Nevertheless, NOX2 clearly contributes to the pathogenesis of many inflammatory diseases, and its inhibition is predicted to provide a novel therapeutic approach. Critical Issues: Possible side effects that might arise from targeting NOX2 are discussed, including the possibility that such inhibition will contribute to increased infections and/or autoimmune disorders. The state of the field with regard to existing NOX2 inhibitors and targeted development of novel inhibitors is also summarized. Future Directions: NOX2 inhibitors show particular promise for the treatment of inflammatory diseases, both acute and chronic. Theoretical side effects include pro-inflammatory and autoimmune complications and should be considered in any therapeutic program, but in our opinion, available data do not indicate that they are sufficiently likely to eliminate NOX2 as a drug target, particularly when weighed against the seriousness of many NOX2-related indications. Model studies demonstrating efficacy with minimal side effects are needed to encourage future development of NOX2 inhibitors as therapeutic agents. Antioxid. Redox Signal. 23,

show abstract

Section: Other Reported Nox Inhibitorsmentioning

confidence: 96%

NOX2 As a Target for Drug Development: Indications, Possible Complications, and Progress

Diebold

Smith

Yang

et al. 2015

Antioxidants & Redox Signaling

106

View full text Add to dashboard Cite

show abstract

“…The xanthine/XO superoxide-generating system has been widely used to determine the superoxide scavenging activity of agents of interest (Wang et al, 1999). The production of superoxide by the xanthine/XO system was very sensitive to the presence of SOD (Fig.…”

Section: Dextromethorphan Protects Dopaminergic Neurons 215mentioning

confidence: 99%

Dextromethorphan Protects Dopaminergic Neurons against Inflammation-Mediated Degeneration through Inhibition of Microglial Activation

Liu

Qin²,

Li³

et al. 2003

J Pharmacol Exp Ther

310

385

View full text Add to dashboard Cite

Inflammation in the brain has increasingly been recognized to play an important role in the pathogenesis of several neurodegenerative disorders, including Parkinson's disease and Alzheimer's disease. Inflammation-mediated neurodegeneration involves activation of the brain's resident immune cells, the microglia, which produce proinflammatory and neurotoxic factors, including cytokines, reactive oxygen intermediates, nitric oxide, and eicosanoids that impact on neurons to induce neurodegeneration. Hence, identification of compounds that prevent microglial activation may be highly desirable in the search for therapeutic agents for inflammation-mediated neurodegenerative diseases. In this study, we report that dextromethorphan (DM), an ingredient widely used in antitussive remedies, reduced the inflammation-mediated degeneration of dopaminergic neurons through inhibition of microglial activation. Pretreatment (30 min) of rat mesencephalic neuron-glia cultures with DM (1-10 M) reduced, in a dose-dependent manner, the microglia-mediated degeneration of dopaminergic neurons induced by lipopolysaccharide (LPS, 10 ng/ml). Significant neuroprotection by DM was also evident when DM was applied to cultures up to 60 min after the addition of LPS. The neuroprotective effect of DM was attributed to inhibition of LPS-stimulated microglial activation because DM significantly inhibited the LPS-induced production of tumor necrosis factor-␣, nitric oxide, and superoxide free radicals. This conclusion was further supported by the finding that DM failed to prevent 1-methyl-4-phenylpyridinium-or ␤-amyloid peptide (1-42)-induced dopaminergic neurotoxicity in neuron-enriched cultures. In addition, because LPS did not produce any significant increase in the release of excitatory amino acids from neuron-glia cultures and N-methyl-D-aspartate antagonist dizocilpine maleate failed to afford significant neuroprotection, it is unlikely that the neuroprotective effect of DM is mediated through N-methyl-D-aspartate receptors. These results suggest that DM may be a promising therapeutic agent for the treatment of Parkinson's disease.

show abstract

“…It has been reported that magnolol, a compound purified from Magnolia officinalis, relaxes rat vascular smooth muscle [2], scavenges hydroxyl radicals [3], inhibits neutrophil aggregation and superoxide anion generation [4,5], suppresses the expression of vascular cell adhesion molecule-1 in endothelial cells [6], inhibits nitric oxide (NO) production in lipopolysaccharide (LPS)-activated macrophages [7]. Recently, it has been reported that the anti-inflammatory effects of magnolol are mediated through inhibition of the downstream pathway of MEKK-1 in NF-κB activation signaling [8].…”

Section: Introductionmentioning

confidence: 99%

Magnolol Inhibits LPS-induced NF-κB/Rel Activation by Blocking p38 Kinase in Murine Macrophages

Kothandan

Cho

et al. 2010

Korean J Physiol Pharmacol

View full text Add to dashboard Cite

ABBREVIATIONS: iNOS, indusible nitric oxide synthase; NF-κB/Rel, nuclear factor κB/Rel; LPS, lipopolysaccharide.Received August 31, 2010, Revised October 31, 2010, Accepted November 10, 2010 Corresponding to: Young Jin Jeon, Department of Pharmacology, School of Medicine, Chosun University, 375, Susuk-dong, (Fax) This study demonstrates the ability of magnolol, a hydroxylated biphenyl compound isolated from M agnolia officinalis, to inhibit LPS-induced expression of iNOS gene and activation of NF-κB/Rel in RAW 264.7 cells. Immunohisto-chemical staining of iNOS and W estern blot analysis showed magnolol to inhibit iNOS gene expression. Reporter gene assay and electrophoretic mobility shift assay showed that magnolol inhibited NF-κB/Rel transcriptional activation and DNA binding, respectively. Since p38 is important in the regulation of iNOS gene expression, we investigated the possibility that magnolol to target p38 for its anti-inflammatory effects. A molecular modeling study proposed a binding position for magnolol that targets the ATP binding site of p38 kinase (3GC7). Direct interaction of magnolol and p38 was further confirmed by pull down assay using magnolol conjugated to Sepharose 4B beads. The specific p38 inhibitor SB203580 abrogated the LPS-induced NF-κB/Rel activation, whereas the selective MEK-1 inhibitor PD98059 did not affect the NF-κB/Rel. Collectively, the results of the series of experiments indicate that magnolol inhibits iNOS gene expression by blocking NF-κB/Rel and p38 kinase signaling.

show abstract

Inhibition by Magnolol of Formylmethionyl-leucyl-phenyl alanine-induced Respiratory Burst in Rat Neutrophils

Cited by 29 publications

References 40 publications

NOX2 As a Target for Drug Development: Indications, Possible Complications, and Progress

NOX2 As a Target for Drug Development: Indications, Possible Complications, and Progress

Dextromethorphan Protects Dopaminergic Neurons against Inflammation-Mediated Degeneration through Inhibition of Microglial Activation

Magnolol Inhibits LPS-induced NF-κB/Rel Activation by Blocking p38 Kinase in Murine Macrophages

Contact Info

Product

Resources

About