Bergamot (Citrus bergamia Risso) fruit extracts and identified components alter expression of interleukin 8 gene in cystic fibrosis bronchial epithelial cell lines

Abstract

BackgroundCystic fibrosis (CF) airway pathology is a fatal, autosomal, recessive genetic disease characterized by extensive lung inflammation. After induction by TNF-α, elevated concentrations of several pro-inflammatory cytokines (i.e. IL-6, IL-1β) and chemokines (i.e. IL-8) are released from airway epithelial cells. In order to reduce the excessive inflammatory response in the airways of CF patients, new therapies have been developed and in this respect, medicinal plant extracts have been studied. In this article we have investigated the possible use of bergamot extracts (Citrus bergamia Risso) and their identified components to alter the expression of IL-8 associated with the cystic fibrosis airway pathology.MethodsThe extracts were chemically characterized by 1H-NMR (nuclear magnetic resonance), GC-FID (gas chromatography-flame ionization detector), GC-MS (gas chromatography-mass spectrometry) and HPLC (high pressure liquid chromatography). Both bergamot extracts and main detected chemical constituents were assayed for their biological activity measuring (a) cytokines and chemokines in culture supernatants released from cystic fibrosis IB3-1 cells treated with TNF-α by Bio-Plex cytokine assay; (b) accumulation of IL-8 mRNA by real-time PCR.ResultsThe extracts obtained from bergamot (Citrus bergamia Risso) epicarps contain components displaying an inhibitory activity on IL-8. Particularly, the most active molecules were bergapten and citropten. These effects have been confirmed by analyzing mRNA levels and protein release in the CF cellular models IB3-1 and CuFi-1 induced with TNF-α or exposed to heat-inactivated Pseudomonas aeruginosa.ConclusionsThese obtained results clearly indicate that bergapten and citropten are strong inhibitors of IL-8 expression and could be proposed for further studies to verify possible anti-inflammatory properties to reduce lung inflammation in CF patients.

Efficacy of bergamot: From anti‐inflammatory and anti‐oxidative mechanisms to clinical applications as preventive agent for cardiovascular morbidity, skin diseases, and mood alterations

“…The in vitro anti-inflammatory activity of flavonoid fraction from bergamot juice, suggesting the activation of SIRT1 and demonstrate the inhibitory effects of BJe on LPS-induced increases in mRNA transcripts and protein levels of pro-inflammatory cytokines such as IL-8 gene expression. (Borgatti et al, 2011;Xie, Zhang, & Zhang, 2013). The antioxidant activity of BJe was focused on the cytoprotective ability of BJe against oxidants, such as hydrogen peroxide (H 2 O 2 ) and (Fe 2 SO 4 ) 3 , that cause oxidative cell damage (Ferlazzo et al, 2015).…”

Evaluation of melanogenesis in A-375 melanoma cells treated with 5,7-dimethoxycoumarin and valproic acid

“…Coumarins are derivatives of -pyrone and are widespread in plants [16]. They are known to be biologically active substances that can protect against reactive oxygen species-mediated damage and they show anti-mutagenic, anticancer and antibacterial properties [17][18][19]. They also cause vasodilation, have anti-thrombotic properties and suppress the activities of lipooxygenases and cyclooxygenases [13].…”

MicroRNA miR-93-5p regulates expression of IL-8 and VEGF in neuroblastoma SK-N-AS cells

“…Cytokines, chemokines and growth factors in tissue culture supernatants released from the cells under analysis were measured by Bio-Plex Pro Human Cytokine 27-Plex Assay (#M50-0KCAF0Y; Bio-Rad Laboratories) as described by the manufacturer (33,34). The Bio-Plex cytokine assay is designed for the multiplex quantitative measurement of multiple cytokines in a single well using as little as 50 µl of sample.…”

“…The Bio-Plex cytokine assay is designed for the multiplex quantitative measurement of multiple cytokines in a single well using as little as 50 µl of sample. Samples were analyzed on a Bio-Rad 96-well plate reader using the Bio-Plex Suspension Array System and Bio-Plex Manager software (Bio-Rad Laboratories) (33,34).…”