1 5-Lipoxygenase Inhibitors and their Anti-inflammatory Activities

Batt, Douglas G.

doi:10.1016/s0079-6468(08)70004-3

Cited by 67 publications

(25 citation statements)

References 336 publications

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“…Conversely, indomethacin increased the exudate volume in subacute CGN-pleurisy (24 h), while the 5-LOX inhibitors, zileuton and BL, inhibited this response. These results are well matched with the previous fi ndings that 5-LOX is important to provoke infl ammatory response in CGN-induced pleurisy (Cuzzocrea et al, 2003) and 5-LOX inhibitors are active on this animal model (Batt, 1992). In contrast, indomethacin inhibits COXs; thus, a considerable amount of arachidonic acid may be converted to LTs by 5-LOX, leading to an increase in the exudate volume in the 24 h model.…”

Section: Discussionsupporting

confidence: 91%

Inhibition of Experimental Lung Inflammation and Bronchitis by Phytoformula Containing Broussonetia papyrifera and Lonicera japonica

Ko¹,

Jin²,

Kwon³

et al. 2011

Biomolecules and Therapeutics

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Many patients suffer from lung infl ammatory disorders including asthma, bronchitis and chronic obstructive pulmonary disorders (COPD). Several classes of drugs including bronchodilators, antitussives, steroids and leukotriene (LT) receptor antagonists have been used to treat these disorders. However, these drugs sometimes do not provide fundamental care, even though the major symptoms are alleviated (Jeffery, 2001). Thus, new effective drugs with novel action mechanism(s) are needed to treat lung infl ammatory disorders. In this regard, natural products may be applied safely for treating human lung infl ammation and bronchitis.The root barks of Broussonetia papyrifera (L.) Vent. (Moraceae) distributed in China, Japan and Korea have been used as anti-infl ammatory and antitussive agents in traditional Chinese medicine, especially for the treatment of older people having bronchitis (Editorial Committee, 1999). Recently, the 95% ethanol extracts of the radix, stems, leaves and fruits of B. papyrifera showed antinociceptive and anti-infl ammatory activity in vivo, with radix having the strongest activity (Lin et al., 2008). Lonicera japonica (Thunb.) (Caprifoliaceae) is a Broussonetia papyrifera and Lonicera japonica have long been used in the treatment of infl ammatory disorders, especially respiratory infl ammation, in Chinese medicine. Previously, phytoformula (BL) containing B. papyrifera and L. japonica was found to exert strong anti-infl ammatory activity in vitro and in vivo. In this study, the effects of BL on lung infl ammation including bronchitis were examined in vitro and in vivo. BL (10-100 μg/ml) inhibited nitric oxide (NO) production of lipopolysaccharide (LPS)-treated alveolar macrophages, MH-S cells, primarily by down-regulating inducible NO synthase. BL also inhibited production of the proinfl ammatory cytokines, TNF-α and IL-6. Against an animal model of pleural cavity infl ammation, BL (200-400 mg/kg) signifi cantly inhibited 5 h and 24 h carrageenan-induced pleurisy in rats when administered orally. Additionally, BL inhibited experimental bronchitis induced by intratracheal instillation of LPS to rats. Taken together, these results indicate that BL may be effective for the treatment of human lung infl ammation as well as bronchitis.

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Section: Discussionsupporting

confidence: 91%

Inhibition of Experimental Lung Inflammation and Bronchitis by Phytoformula Containing Broussonetia papyrifera and Lonicera japonica

Ko¹,

Jin²,

Kwon³

et al. 2011

Biomolecules and Therapeutics

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“…A number of pharmacologic antagonists for this pathway are being used in specific clinical settings (17). Inhibitors of 5-lipoxygenase (5-LO) metabolism have shown promise in the treatment of asthma and shock with limited side effects in preclinical and clinical trials (18,19).…”

Section: Introductionmentioning

confidence: 99%

Growth control of lung cancer by interruption of 5-lipoxygenase-mediated growth factor signaling.

Avis¹,

Jett²,

Boyle³

et al. 1996

J. Clin. Invest.

223

143

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“…However, further antiinflammatory activity of MK-886 cannot be excluded. 28 In addition, investigations with MK-886 treatment over a longer time period has been performed in earlier studies 29 and reduction of fibrosis development has been shown.…”

Section: Cys-lt and Liver Injury M Op Den Winkel Et Almentioning

confidence: 98%

Role of cysteinyl-leukotrienes for portal pressure regulation and liver damage in cholestatic rat livers

Winkel

Gmelin

Schewe

et al. 2013

Laboratory Investigation

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Kupffer cells (KCs) have a major role in liver injury, and cysteinyl-leukotrienes (Cys-LTs) are known to be involved as well. The KC-mediated pathways for the production and secretion of Cys-LT in cholestatic liver injury have not yet been elucidated. Here, we hypothesized that KC activation by Toll-like receptor ligands results in Cys-LT-mediated microcirculatory alterations and liver injury in acute cholestasis. We hypothesized further that this situation is associated with changes in the secretion and production of Cys-LT. One week after bile duct ligation (BDL), livers showed typical histological signs of cholestatic liver injury. Associated microcirculatory disturbances caused increased basal and maximal portal pressure following KC activation. These differences were determined in BDL livers compared with shamoperated livers in vivo (KC activation by LPS 4 mg/kg b.w.) and in isolated perfused organs (KC activation by Zymosan A, 150 mg/ml). Treatment with the 5-lipoxygenase inhibitor MK-886 alone did not alter portal perfusion pressure, lactate dehydrogenase (LDH) efflux, or bile duct proliferation in BDL animals. Following KC activation, portal perfusion pressure increased. The degree of cell injury was attenuated by MK-886 (3 mM) treatment as estimated by LDH efflux. In normal rats, a large amount of Cys-LT efflux was found in the bile. Only a minor amount was found in the effluent perfusate. In BDL livers, the KC-mediated Cys-LT efflux into the sinusoidal system increased, although the absolute Cys-LT level was still grossly lower than the biliary excretion in sham-operated livers. In conclusion, our results indicate that treatment with Cys-LT inhibitors might be a relevant target for attenuating cholestatic liver damage.

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1 5-Lipoxygenase Inhibitors and their Anti-inflammatory Activities

Cited by 67 publications

References 336 publications

Inhibition of Experimental Lung Inflammation and Bronchitis by Phytoformula Containing Broussonetia papyrifera and Lonicera japonica

Inhibition of Experimental Lung Inflammation and Bronchitis by Phytoformula Containing Broussonetia papyrifera and Lonicera japonica

Growth control of lung cancer by interruption of 5-lipoxygenase-mediated growth factor signaling.

Role of cysteinyl-leukotrienes for portal pressure regulation and liver damage in cholestatic rat livers

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