ABSTRACT
Bioassay-guided fractionation of Acicarpha tribuloides Juss. resulted in the isolation of an uncommon non-glycosylated secoiridoid, tribulolide (1), two known secoiridoid glycosides named secologanic acid (2) and vogeloside (3) as well as two natural chromones, 6,7-dimethoxychromone (4) and 7-hydroxy-6-methoxy-chromone (5). Compounds 1-3 showed inhibition of nitric oxide production in lipopolysaccharide-activated macrophages; their activity is comparable to that of aminoguanidine, a classic inhibitor.
Subject(s)
Iridoids/chemistry , Iridoids/pharmacology , Lipopolysaccharides/pharmacology , Macrophages/drug effects , Macrophages/metabolism , Magnoliopsida/chemistry , Nitric Oxide/biosynthesis , Animals , Iridoids/isolation & purification , Magnetic Resonance Spectroscopy , Molecular Structure , RatsABSTRACT
The integration of innate and adaptive immune responses is required for efficient control of Candida albicans. The present work aimed to assess, at the local site of the infection, the immunocompetence of macrophages in rats infected intraperitoneally with C. albicans and exposed simultaneously to stress during 3 days (CaS group). We studied the 1) ability to remove and kill C. albicans, 2) tumor necrosis factor-alpha (TNF-alpha) release, 3) balance of the inducible enzymes NO synthase (iNOS) and arginase, and 4) expression of interleukin (IL)-1beta and IL-1 receptor antagonist (ra) mRNA. Compared with only infected animals (Ca group), the number of colony-forming units was significantly higher in CaS rats (P < 0.01), and the macrophage candidicidal activity was approximately 2.5-fold lower (P < 0.01). Release of TNF-alpha was diminished in both unstimulated and heat-killed C. albicans restimulated macrophages of the CaS group (Ca vs. CaS, P < 0.03 and P < 0.05, respectively). In Ca- and CaS-group rats, the rates for both the arginase activity and the NO synthesis were significantly enhanced. However, the stress exposure downregulated the activity of both enzymes (CaS vs. Ca, P < 0.05). After in vitro restimulation, the IL-1ra/IL-1beta ratio was significantly diminished in CaS-group rats (P < 0.05). Our results indicate that a correlation exists between early impairment of macrophage function and stress exposure.
