Abstract
Extracts from Nigella arvensis L. seeds, which are widely used as anti-inflammatory remedies in traditional medicine of Northern Africa, were able to inhibit the expression of the pro-inflammatory neutrophil chemokine Interleukin (IL)-8 in Cystic Fibrosis (CF) bronchial epithelial IB3-1 cells exposed to the Gram-negative bacterium Pseudomonas aeruginosa. The chemical composition of the extracts led to the identification of three major components, β-sitosterol, stigmasterol, and campesterol, which are the most abundant phytosterols, cholesterol-like molecules, usually found in plants. β-sitosterol (BSS) was the only compound that significantly reproduced the inhibition of the P. aeruginosa-dependent expression of IL-8 at nanomolar concentrations. BSS was tested in CF airway epithelial CuFi-1 cells infected with P. aeruginosa. BSS (100 nM), showed a significant and consistent inhibitory activity on expression of the P. aeruginosa-stimulated expression chemokines IL-8, GRO-α GRO-β, which play a pivotal role in the recruitment of neutrophils in CF inflamed lungs. Preliminary mechanistic analysis showed that BSS partially inhibits the P. aeruginosa-dependent activation of Protein Kinase C isoform alpha, which is known to be involved in the transmembrane signaling activating IL-8 gene expression in bronchial epithelial cells. These data indicate BSS as a promising molecule to control excessive lung inflammation in CF patients.
Highlights
Medicinal plants are attracting a renewed interest, since they have been a classical source of drugs for different human diseases (Newman and Cragg, 2016)
These results indicate that incubation with N. arvensis extract for 24 h does not affect the adherence of PAO1 to IB3-1 cells, suggesting that the sharp inhibition of P. aeruginosa-dependent IL-8 transcription after treatment with
In search of novel anti-inflammatory molecules to reduce the adverse effects of chronic lung inflammation in Cystic Fibrosis (CF) patients, we were inspired by serendipity on the potential activities of black seeds collected from the deserts of Northern Africa (Morocco) and distributed by Berber pharmacists (Supplementary Text S1)
Summary
Medicinal plants are attracting a renewed interest, since they have been a classical source of drugs for different human diseases (Newman and Cragg, 2016). This interest is actual as the introduction of new drugs is largely adopting the repurposing strategy to overcome the bottlenecks of pharmaceutical development (Strittmatter, 2014), a strategy that includes the natural medicinal products as potential repurposing source (Cragg et al, 2014). Few findings were reported about extracts derived from N. arvensis or active principles identified in this species, while N. sativa was the object of different studies, reporting on different biological effects including its anti-inflammatory activities (Khader and Eckl, 2014). Nigella seeds contain sterols, proteins, alkaloids, saponins, and essential oils (Khader and Eckl, 2014)
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