Inhibition of monosodium urate crystal-induced inflammation by scopoletin and underlying mechanisms

Yao, Xiujuan; Ding, Zhongxiang; Xia, Yufeng; Wei, Zhifeng; Luo, Yubin; Feleder, Carlos; Dai, Yue

doi:10.1016/j.intimp.2012.07.024

Cited by 38 publications

(28 citation statements)

References 44 publications

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“…Our results show that scopoletin inhibition of leukocyte migration to the pleural cavity was due to decreased neutrophil migration. This result corroborates Yao et al [31], who showed similar anti-inflammatory profile in a monosodium urate crystal-induced inflammation model in vivo in which scopoletin was able to decrease the neutrophil migration and activation to the inflammation site. Furthermore, the decrease in neutrophils expressed in our results is accompanied by significant inhibition of MPO activity.…”

Section: Discussionsupporting

confidence: 92%

Inhibition of the NF-κB and p38 MAPK pathways by scopoletin reduce the inflammation caused by carrageenan in the mouse model of pleurisy

Nascimento

Arruda‐Silva

Luz

et al. 2016

Immunopharmacology and Immunotoxicology

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Natural products have long been used worldwide as therapeutic agents, but it is only recently, in response to the new challenges posed by global population aging, that interest in research into potentially therapeutic natural products has reemerged. In this context, coumarins, chemical compounds found in plants that have known anti-inflammatory activity, are promising candidates for the development of new drugs. In this study we test the effect of scopoletin, a coumarin found in several plant species, on carrageenan-induced inflammation in the mouse model of pleurisy. Initially, the effects of scopoletin on leukocyte migration and exudate concentrations were evaluated at three different doses (0.1, 1 and 5 mg/kg) and time (0.5-4 h before pleurisy). In the next step, we chose the lowest dose capable of inhibiting the inflammatory parameters (1 mg/kg), in order to analyze the myeloperoxidase and adenosine deaminase activities, the nitric oxide, tumor necrosis factor-α, and interleukin 1β levels in the fluid leakage, and the p65 subunit of NF-κB and p38 MAPK phosphorylation. Scopoletin at a dose of 1 mg/kg was able to significantly reduce cell migration and exudation to the pleural fluid (p < 0.01). Scopoletin at the same dose also decreased the myeloperoxidase and adenosine-deaminase activities and nitric oxide, tumor necrosis factor-α, and interleukin-1β levels (p < 0.01). In addition, it significantly reduced p65 and p38 phosphorylation in the mouse lungs (p < 0.01). Our results reinforce that scopoletin has important anti-inflammatory activity, and shows, that this effect can be attributed to the ability of this compound to inhibit the phosphorylation of NF-κB and p38 MAPK.

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Section: Discussionsupporting

confidence: 92%

Inhibition of the NF-κB and p38 MAPK pathways by scopoletin reduce the inflammation caused by carrageenan in the mouse model of pleurisy

Nascimento

Arruda‐Silva

Luz

et al. 2016

Immunopharmacology and Immunotoxicology

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“…[29][30][31] For example, the antiinflammatory effect of diclofenac, one of the NSAIDs, has been examined in air pouch animal model. 25 Diclofenac inhibits leukocyte influx and reduces inflammatory mediator levels in pouch fluids.…”

Section: Discussionmentioning

confidence: 99%

Mast Cell Stabilizer Ketotifen Inhibits Gouty Inflammation in Rats

Hsu

Chu

Chen

et al. 2016

American Journal of Therapeutics

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Gout, an extremely painful arthritis with relapsing inflammatory attacks, is a common inflammatory joint disease in adults. We examined the therapeutic effect of ketotifen, a mast cell stabilizer, on monosodium urate (MSU) crystal-induced acute inflammation. Eight-week-old male Wistar rats were injected with MSU crystals (5 mg per rat) into air pouch. Ketotifen (0, 0.1, 03, and 1 mg/kg) was given 1 hour before MSU crystal injection. Lavage histamine, leukocyte counts, mast cell counts, nitric oxide, and proinflammatory mediator levels were assessed 12 hours after MSU injection. Ketotifen significantly inhibited MSU-induced mast cell activation and histamine concentration in air pouch lavage. Ketotifen dose-dependently inhibited MSU-initiated leukocyte infiltration into the air pouch. Furthermore, ketotifen significantly decreased proinflammatory mediators, including nitric oxide, interleukin-1β, and interleukin-6, production in MSU-treated rats. Ketotifen may attenuate MSU-induced acute inflammation by inhibiting mast cell activation and leukocyte infiltration in rats. Furthermore, ketotifen has the potential to be a new approach in managing patients with gouty inflammation in the future.

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“…To date, most of the investigations on the therapeutic efficacy of scopoletin in vivo have focused on systemic disorders. In vivo studies have demonstrated that scopoletin is able to ameliorate the symptoms of various inflammatory, rheumatoid and digestive disorders [42,43].…”

Section: Discussionmentioning

confidence: 99%

UPEI-400, a Conjugate of Lipoic Acid and Scopoletin, Mediates Neuroprotection in a Rat Model of Ischemia/Reperfusion

Connell

Saleh

Rajagopal

et al. 2016

Preprint

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1) Background: Previously, our laboratory has provided evidence that pre-administration of the antioxidant, lipoic acid covalently bonded to various naturally occurring antioxidants, enhanced neuroprotective capacity compared to the administration of lipoic acid on its own. The naturally occurring compound scopoletin, a coumarin derivative, has been shown in various in vitro studies to have both antioxidant and anti-inflammatory mechanism of actions. To date, the effect of scopoletin on neuronal cell death in an in vivo model of ischemia or ischemia-reperfusion has not been investigated. Therefore, the present investigation was designed to determine if scopoletin on its own, or a co-drug consisting of lipoic acid and scopoletin covalent bond, named UPEI-400, would be capable of demonstrating a similar neuroprotective efficacy.2) Methods: Using a rodent model of stroke in male rats (anesthetized with Inactin®; 100 mg/kg, iv), the middle cerebral artery was permanently occluded for 6 hours (pMCAO), or in separate animals, occluded for 30 min followed by 5.5 hrs of reperfusion (ischemia/reperfusion; I/R).3) Results: Pre-administration of either scopoletin or UPEI-400 significantly decreased infarct volume in the I/R model (p<0.05), but not in the pMCAO model of stroke.However, UPEI-400 was ~1000 times more potent as compared to scopoletin on its own.The optimal dose of UPEI-400 was then injected during the occlusion and at several time points during reperfusion and significant neuroprotection was observed for up to 150 mins following the start of reperfusion (p<0.05). 4) Conclusion:The data suggest that synthetic combination of scopoletin with lipoic acid (UPEI-400) is a more effective neuroprotectant that either compound on their own. Also, since UPEI-400 was only effective in a model of I/R, it is possible that it may act to Preprints (www.preprints.org) | NOT PEER-REVIEWED |

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Inhibition of monosodium urate crystal-induced inflammation by scopoletin and underlying mechanisms

Cited by 38 publications

References 44 publications

Inhibition of the NF-κB and p38 MAPK pathways by scopoletin reduce the inflammation caused by carrageenan in the mouse model of pleurisy

Inhibition of the NF-κB and p38 MAPK pathways by scopoletin reduce the inflammation caused by carrageenan in the mouse model of pleurisy

Mast Cell Stabilizer Ketotifen Inhibits Gouty Inflammation in Rats

UPEI-400, a Conjugate of Lipoic Acid and Scopoletin, Mediates Neuroprotection in a Rat Model of Ischemia/Reperfusion

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