Kaurane diterpenes protect against apoptosis and inhibition of phagocytosis in activated macrophages

Abstract

Background and purpose: The kaurane diterpenes foliol and linearol are inhibitors of the activation of nuclear factor kB, a transcription factor involved in the inflammatory response. Effects of these diterpenes on apoptosis and phagocytosis have been analysed in cultured peritoneal macrophages and in the mouse macrophage cell line, RAW 264.7. Experimental approach: Macrophages were maintained in culture and activated with pro-inflammatory stimuli in the absence or presence of diterpenes. Apoptosis and the phagocytosis in these cells under these conditions were determined. Key results: Incubation of macrophages with a mixture of bacterial lipopolysaccharide (LPS)/interferon-g (IFN-g) induced apoptosis through a NO-dependent pathway, an effect significantly inhibited by foliol and linearol in the low mM range, without cytotoxic effects. Apoptosis in macrophages induced by NO donors was also inhibited. The diterpenes prevented apoptosis through a mechanism compatible with the inhibition of caspase-3 activation, release of cytochrome c to the cytosol and p53 overexpression, as well as an alteration in the levels of proteins of the Bcl-2 family, in particular, the levels of Bax. Cleavage of poly(ADP-ribose) polymerase, a well-established caspase substrate, was reduced by these diterpenes. Treatment of cells with foliol and linearol decreased phagocytosis of zymosan bioparticles by RAW 264.7 cells and to a greater extent by peritoneal macrophages. Conclusions and implications: Both diterpenes protected macrophages from apoptosis and inhibited phagocytosis, resulting in a paradoxical control of macrophage function, as viability was prolonged but inflammatory and phagocytic functions were impaired.

Cyclooxygenase (COX)-1 and -2 Inhibitory Labdane Diterpenes from Crassocephalum mannii

“…The only differences were the disappearance of a carboxylic acid group, an olefinic methyl group (CH 3 -16), and an olefinic proton (H-14) in compound 2 and the appearance of a new multiplet corresponding to oxygenated methylene protons at δ H 3.78 and 3.46. Inspection of HMQC and DEPT spectra of 2 confirmed the presence of three methyls, eight methylenes, two methines, and three quaternary carbons ( Table 1) 13 C, HMQC, and DEPT NMR spectroscopic inspection of the aglycon moiety of 3a confirmed the presence of four methyls, nine methylenes, three methines, and four quaternary carbons ( Table 1). Two of the methylene carbons were oxygenated at δ C 61.5 (δ H 4.55) and 72.7 (δ H 3.58/3.83), and on the basis of 2J and 3J correlations from the methyl protons at C-20 and C-16, respectively, observed in the HMBC spectrum, the methylene carbons at δ C 61.5 and 72.7 could be assigned to C-15 and C-19, in turn.…”

“…12,13 For use in traditional medicine Crassocephalum tea is prepared from fresh plants (500 g plant material/L H 2 O) and consumed three times daily until pain subsides.…”

Bupleurum Polysaccharides Attenuates Lipopolysaccharide-Induced Inflammation via Modulating Toll-Like Receptor 4 Signaling

“…The phagocytosis was assayed by detecting ingestion of E.coli fluorescent particles by macrophages [20]. Macrophages (2×10 5 cells/ml) were placed in 24-well culture plates and treated with different concentrations of BPs for 30 min.…”

Evaluation of antinociceptive effects of Crassocephalum bauchiense Hutch (Asteraceae) leaf extract in rodents

“…Well accepted that many plant-derived compounds possess analgesic and anti-inflammatory properties. Recent studies have shown that the labdane diterpene of the air-dried parts of Crassocephalum mannii has anti-inflammatory activity through its cyclooxygenase inhibitory activity (Heras et al, 2007;Liua et al, 2006;MohamedElamir et al, 2008). Although the potent activity of non-steroidal anti-inflammatory drugs is noteworthy, they have also many severe adverse effects.…”