Inhibition of COX-2 and NF-κB1 Gene Expression, NO Production, 5-LOX, and COX-1 and COX-2 Enzymes by Extracts and Constituents of Onopordum acanthium

Abstract

The present study focused on the investigation of the inhibition of cyclooxygenase-2 and nuclear factor kappa B1 gene expression, nitric oxide production, leukotriene biosynthesis (5-lipoxygenase), and cyclooxygenase-1 and cyclooxygenase-2 enzymes of Onopordum acanthium, and the isolation and identification of its active compounds. From the chloroform soluble part of the MeOH extract prepared from aerial parts, lignans [pinoresinol (1), syringaresinol (2), and medioresinol (3)] and flavonoids [hispidulin (4), nepetin (5), apigenin (6), and luteolin (7)] were isolated by a combination of different chromatographic methods. The structures of the compounds were determined by means of mass spectrometry and 1D- and 2D-nuclear magnetic resonance spectroscopy, and by comparison of the spectral data with literature values. Extracts of different polarity and the isolated compounds obtained from the aerial parts, together with those previously isolated from the roots of the plant [4β,15-dihydro-3-dehydrozaluzanin C (8), zaluzanin C (9), 4β,15,11β,13-tetrahydrozaluzanin C (10), nitidanin diisovalerianate (11), 24-methylenecholesterol (12), and 13-oxo-9Z,11E-octadecadienoic acid (13)], were evaluated for their inhibitory effects on cyclooxygenase-2 and nuclear factor kappa B1 gene expression, inducible nitric oxide synthase, 5-lipoxygenase, and cyclooxygenase-1 and cyclooxygenase-2 enzymes in in vitro assays. It was found that O. acanthium extracts exert strong inhibitory activities in vitro and some lignans, flavonoids, and sesquiterpenes may play a role in these activities. 4β,15-Dihydro-3-dehydrozaluzanin C and zaluzanin C at 20 µM were the most active constituents tested against lipopolysaccharide/interferon-γ-induced nitric oxide production (100.4 ± 0.5 % and 99.4 ± 0.8 %) in the inhibition of cyclooxygenase-2 (98.6 ± 0.2 % and 97.0 ± 1.1 %) and nuclear factor kappa B1 gene expression (76.7 ± 7.3 % and 69.9 ± 3.4 %). Furthermore, it was shown that these inhibitory effects are not due to cytotoxicity of the compounds.

In-vitro antioxidant, Xanthine oxidase-inhibitory and in-vivo Anti-inflammatory, analgesic, antipyretic activity of <em>Onopordum acanthium</em>

“…hispidulin, nepetin, apigenin and luteolin from the aerial parts of O. acanthium [11]. These findings are similar to our identified phenolic contents, nepetin, apigenin and luteolin belongs flavone group of flavonoids, additionally gallic acid: a tannin was identified in our sample.…”

“…[8,9,10]. Laijter et al reported in-vitro COX-2 and NF-κB1 gene expression, iNOS, 5-LOX, and COX-1 and COX-2 enzymes inhibitory effects of O. acanthium [11]. Previously we reported in-vitro pro-apoptotic and cytotoxic effect of Onopordum acanthium crude extract against glioblastoma U-373 cells (10).…”

Modulation of gut microbiota and delayed immunosenescence as a result of syringaresinol consumption in middle-aged mice

“…SYR has been reported to exert various health-promoting effects, including antioxidant, antistress, antitumorigenic, and anti-inflammatory effects262728. These diverse bioactivities of SYR, like other dietary polyphenols, depend on bacterial transformation by the gut microbiota29.…”

Biologically active secondary metabolites from Asteraceae and Polygonaceae species

“…128 The absorbance was determined with a microplate reader (TACEN Rainbow) at a wavelength of 490 nm, and the reference wavelength was 650 nm.…”

“…128 Human neutrophilic granulocytes with 5-LOX activity were isolated from venous human blood, on the basis of sedimentation rates and lysis tolerance. The concentration of LTB 4 formed during incubation was determined by means of a competitive LTB 4 EIA Kit (Cayman Chemical Company, Ann Arbor, MI, USA).…”