Effect of Serenoa repens, lycopene, and selenium on proinflammatory phenotype activation: an in vitro and in vivo comparison study.
OBJECTIVE
To investigate the antiinflammatory activity of Serenoa repens (SeR), LY, and) on proinflammatory phenotype in rat peritoneal macrophages (Ms) stimulated with Salmonella enteritidis lipopolysaccharide (LPS) and in the prostate of rats with partial bladder outlet obstruction. SeR, combined with other compounds, such as LY and Se is used to relieve symptoms associated with benign prostatic hyperplasia (BPH). Inflammation plays a pivotal role in the pathogenesis of BPH and represents a target for anti-BPH drugs.


METHODS
After stimulation with 1 μg/mL of LPS, peritoneal rat MΦs were coincubated with LY (2 μg/mL), Se (0.03 μg/mL), and SeR (10 μg/mL), alone or in association (LY-Se-SeR) and with RPMI. Inducible cyclooxygenase (COX-2), 5-lypoxygenase (5-LOX), inducible nitric oxide synthase (iNOS), and inhibitor κBα (IκB-α) protein were evaluated by Western blot. Nuclear factor-kappa B (NF-κB) binding activity was measured by electrophoretic mobility shift assay. Tumor necrosis factor-α (TNF-α) gene expression was investigated by real-time polymerase chain reaction. We also evaluated malondialdehyde (MDA) and nitrite levels.


RESULTS
LPS stimulation produced a proinflammatory phenotype in rat peritoneal MΦs. LY, Se, and SeR inhibited the inflammatory cascade, but the Ly-Se-SeR association caused a greater inhibitory effect on the expression of COX-2, 5-LOX, and iNOS. The Ly-Se-SeR association showed a higher efficacy in reducing the loss of IκB-α, the increased NF-κB binding activity, the enhanced mRNA levels of TNF-α, the elevated MDA, and nitrite content. The LY-Se-SeR association in vivo caused a greater inhibitory effect on prostate inflammation induced in rats by partial bladder outlet obstruction.


CONCLUSIONS
The LY-Se-SeR association might be useful in the treatment of BPH.
Department of Urology, Policlinic Hospital, University of Catania, Italy.
Giulio
G
Bonvissuto
Letteria
L
Minutoli
Giuseppe
G
Morgia
Alessandra
A
Bitto
Francesca
F
Polito
Natasha
N
Irrera
Herbert
H
Marini
Francesco
F
Squadrito
Domenica
D
Altavilla
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002338:Carotenoids / Q000494:pharmacology*; D002478:Cells, Cultured; D020672:I-kappa B Proteins / Q000187:drug effects* / Q000235:genetics*; D007249:Inflammation / Q000276:immunology; D000077276:Lycopene; D017737:Macrophages, Peritoneal / Q000187:drug effects*; D008297:Male; D000072000:NF-KappaB Inhibitor alpha; D010641:Phenotype; D011467:Prostate / Q000187:drug effects / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012643:Selenium / Q000494:pharmacology*; D028024:Serenoa; D001748:Urinary Bladder Neck Obstruction / Q000276:immunology
D000975:Antioxidants; D020672:I-kappa B Proteins; C000606206:Nfkbia protein, rat; D000072000:NF-KappaB Inhibitor alpha; D002338:Carotenoids; D012643:Selenium; D000077276:Lycopene