Inhibitors of 5-lipoxygenase: a therapeutic potential yet to be fully realized?

Young, Robert N.

doi:10.1016/s0223-5234(99)00225-1

Cited by 132 publications

(58 citation statements)

References 78 publications

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“…The inhibitory activity was found to be in the order of PSPE (IC 50 An increased level of lipid peroxidation is reported in psoriasis which is mediated by lipoxygenases (LOXs) enzymes utilizing the arachidonic acid pathway. The LOXscatalyzed oxygenation products are apparently involved in the development of psoriasis (Young, 1999) and hence inhibiting the lipoxygenase pathway may be helpful in psoriasis. Therefore, we evaluated the extracts for lipoxygenase inhibition activity and results are presented in Figure 4.…”

Section: Resultsmentioning

confidence: 99%

Assessment ofin vitroantipsoriatic activity of selected Indian medicinal plants

Singh

Chouhan

Sahu

et al. 2015

Pharmaceutical Biology

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Context: Phyllanthus simplex Retz. (Phyllanthaceae), Crotolaria juncea Linn. (Leguminosae), Leucas aspera Linn. (Lamiaceae), and Vitex glabrata R.Br. (Verbenaceae) are well-known Indian medicinal plants. Different parts of these plants are used for healing purposes traditionally in the treatment of psoriasis and various other disorders. This prompted us to assess the antipsoriatic activities of these plants. Objectives: Petroleum ether and ethanol extracts of the selected plants, i.e., P. simplex (whole plant), C. juncea (seeds), L. aspera (aerial parts), and V. glabrata (leaves) were investigated for their in vitro antipsoriatic activity. Materials and methods: Antipsoriatic activity of the extracts was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, using HaCaT cells. About 200 ml of different concentrations (25, 50, 100, 200, and 400 mg/ml) of test samples were prepared in the cell culture medium and incubated for 24 h before MTT assay to determine the viable cells. The effect of these extracts on nitric oxide (NO) production and lipid peroxidation was also evaluated. Results: Our findings revealed that these plants showed promising skin keratinocyte antiproliferative activity. However, the petroleum ether extract of C. juncea (CJPE) and ethanol extract of L. aspera (LAEE) were found to exhibit significant activity (IC 50 value ¼ 45.45 and 55.36 mg/ml, respectively). Discussion and conclusions: The inhibitory action against NO production and lipid peroxidation in HaCaT cells suggested that the antipsoriatic activity of the extracts was mediated by an antioxidant mechanism. These findings validate the claims of the use of these plants in the treatment of psoriasis.

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Section: Resultsmentioning

confidence: 99%

Assessment ofin vitroantipsoriatic activity of selected Indian medicinal plants

Singh

Chouhan

Sahu

et al. 2015

Pharmaceutical Biology

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“…This up-regulation of LOX has been associated with various adverse effects, such as asthma. LOX-5 has been shown to be involved in the production of LTs, which are known to contribute to the progression of osteoarthritis, asthma, and inflammation [11][12][13][14] the oxidation of low-density lipoprotein (LDL), which ultimately causes atherosclerosis 15,16 . Most recently, it has also been demonstrated that increased expression of LOX-12/LOX-15 causes heart failure, in transgenic mice 17 .…”

Section: Research Articlementioning

confidence: 99%

Synthesis and biological evaluation of 2,5-disubstituted 1,3,4-oxadiazole derivatives with both COX and LOX inhibitory activity

Akhter

Alam

et al. 2011

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…Inhibitors of leukotriene (LT) synthesis, 5-LO and FLAP inhibitors, and also CysLT1 receptor antagonists have been shown to be effective in reducing asthma symptoms in children and adults (33). Increased concentrations of urinary LTE 4 were seen with infants with RSV bronchiolitis compared with control subjects without respiratory infection (31).…”

Section: Respiratory Syncytial Virus (Rsv) (Family Paramyxoviridae)mentioning

confidence: 99%

“…Inhibitors of LT synthesis, 5-LO and FLAP inhibitors, and CysLT1 receptor antagonists have been shown to be effective in reducing asthma symptoms (23,33). 5-LO and FLAP inhibitors have the potential advantage over CysLT1 receptor antagonists of reducing activation of all LT inflammatory and allergic responses (9,33).…”

Section: Vol 16 2009 Leukotriene Inhibitor Reduces Viral Allergy Eymentioning

confidence: 99%

A Novel 5-Lipoxygenase-Activating Protein Inhibitor, AM679, Reduces Inflammation in the Respiratory Syncytial Virus-Infected Mouse Eye

Musiyenko

Correa²,

Stock³

et al. 2009

Clin Vaccine Immunol

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Respiratory syncytial virus (RSV) is an important cause of viral respiratory disease in children, and RSV bronchiolitis has been associated with the development of asthma in childhood. RSV spreads from the eye and nose to the human respiratory tract. Correlative studies of humans and direct infection studies of BALB/c mice have established the eye as a significant pathway of entry of RSV to the lung. At the same time, RSV infection of the eye produces symptoms resembling allergic conjunctivitis. Cysteinyl leukotrienes (CysLTs) are known promoters of allergy and inflammation, and the first step in their biogenesis from arachidonic acid is catalyzed by 5-lipoxygenase (5-LO) in concert with the 5-LO-activating protein (FLAP). We have recently developed a novel compound, AM679, which is a topically applied and potent inhibitor of FLAP. Here we show with the BALB/c mouse eye RSV infection model that AM679 markedly reduced the RSV-driven ocular pathology as well as the synthesis of CysLTs in the eye. In addition, AM679 decreased the production of the Th2 cell cytokine interleukin-4 but did not increase the viral load in the eye or the lung. These results suggest that FLAP inhibitors may be therapeutic for RSV-driven eye disease and possibly other inflammatory eye indications. Respiratory syncytial virus (RSV) (family Paramyxoviridae)is an enveloped virus with a single-stranded negative-sense RNA genome of 15.2 kb (8). Human RSV is the leading worldwide viral agent of serious pediatric respiratory tract disease (11). In the United States, ϳ100,000 children under 1 year of age are hospitalized with severe RSV infection, and approximately 90% of all children have been infected one or more times by 2 years of age (11). There is no effective treatment for severe RSV infections, but with high-risk children the RSVneutralizing antibody palivizumab (Synagis) can be used to prevent the development of the disease (6). RSV bronchiolitis is associated with the development of wheezing symptoms and asthma in childhood, and RSV is also a significant cause of morbidity and mortality in the elderly and severely immunocompromised patients (11,12).Inoculation of RSV to the human nose or eyes results in viral replication, with an incubation period of 4 to 5 days, and the virus can then spread to the lower respiratory tract (8). This reflects the anatomical connection between the optic and nasal/upper respiratory tissues, and it is known that the use of eye goggles and nose masks significantly reduces RSV infection from patients to hospital workers (16). With BALB/c mice, instillation of RSV in the eye leads to eye infection, inflammation, and eye-to-lung viral transmission, resulting in respiratory pathology (3). In addition, many chemokines and receptors and interleukin 1␣ (IL-1␣) and tumor necrosis factor (TNF) were induced in the RSV-infected mouse eyes (3). In this study, application of anti-RSV small interfering RNA to the eyes 30 min prior to RSV inoculation prevented both viral growth and virus-induced pathology in the eye and lun...

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Inhibitors of 5-lipoxygenase: a therapeutic potential yet to be fully realized?

Cited by 132 publications

References 78 publications

Assessment ofin vitroantipsoriatic activity of selected Indian medicinal plants

Assessment ofin vitroantipsoriatic activity of selected Indian medicinal plants

Synthesis and biological evaluation of 2,5-disubstituted 1,3,4-oxadiazole derivatives with both COX and LOX inhibitory activity

A Novel 5-Lipoxygenase-Activating Protein Inhibitor, AM679, Reduces Inflammation in the Respiratory Syncytial Virus-Infected Mouse Eye

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