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

Abstract

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.

Comparative Chemomapping of Phytoconstituents from Different Extracts of Globe Artichoke - Cynara Scolymus L.

“…Cinnamaldehyde is found in both of our artichoke extracts, and it was shown by others to ameliorate the induced cardiac dysfunction in rats by inhibiting ROS production and autophagy through TLR4-NOX4 pathway and exhibits anti-inflammatory activity [32]. Similarly to others [33], we were able to identify the scopoletin in artichoke leaves hydro-alcoholic extracts, and it was suggested to have an important anti-inflammatory activity by inhibiting the phosphorylation of NF-κB and p38 MAPK in mice [34].…”

Malva parviflora extract ameliorates the deleterious effects of a high fat diet on the cognitive deficit in a mouse model of Alzheimer’s disease by restoring microglial function via a PPAR-γ-dependent mechanism

“…A proposed anti-inflammatory mechanism for oleanolic acid involves the upregulation of the transcription factor Nrf2, which inhibits the expression of NF-κB [42]. As oleanolic acid, the scopoletin anti-inflammatory effect also involves the inhibition of the NF-κB and p38 MAPK pathways [57]. Congruent with oleanolic acid and scopoletin anti-NF-κB activity, here, we demonstrate that the MpHE decreases the NF-κB activation in a concentration-dependent manner.…”

Blood pressure lowering effect of scopoletin on oxidative stress-associated hypertensive rats

“…These plants produce scopoletin with different amount and can reach 700 nmol/g of fresh weight of the plant [4]. Following some reports on the traditional use of these plants, many studies have revealed that scopoletin exhibits some interesting pharmacological properties, ranging from anti-infectious, cytotoxicity, antiinflammatory, and those acting within the cardiovascular system [4][5][6][7][8]. In addition, some in vitro studies prove that scopoletin exhibits a potent antioxidant activity that makes this chemical even more potential for drug development [9][10][11].…”