RESUMO
Magnolol, a phenolic compound isolated from a Chinese herbal drug, Magnolia officinalis, has been shown to protect rat heart from ischemia/reperfusion injury. Neutrophil adhesion plays a crucial process during this inflammatory response. To evaluate whether magnolol prevents ischemia/reperfusion injury by inhibiting neutrophil adhesion, we determined whether magnolol can inhibit adhesion of phorbol-12-myristate-13-acetate (PMA)-activated human neutrophils to a fibrinogen-coated surface in a dose-dependent manner. Using flow cytometric analysis, we observed that magnolol pretreatment (10 min at 37 degrees C) diminished PMA (100 ng/ml)-induced Mac-1 upregulation. PMA also induced rapid intracellular accumulation of superoxide (O2-.) and hydrogen peroxide (H2O2) in neutrophils; magnolol pretreatment attenuated the accumulation of these two substances. Inhibition of reactive oxygen species by superoxide dismutase and/or catalase, which decompose O2-. and H2O2, respectively, also abolished Mac-1 upregulation and neutrophil adhesion. We conclude that magnolol inhibits neutrophil adhesion and that this can account for its anti-ischemia/reperfusion injury effect. We propose that the inhibitory effect of magnolol on neutrophil adhesion to the extracellular matrix is mediated, at least in part, by inhibition of the accumulation of reactive oxygen species, which in turn suppresses the upregulation of Mac-1 that is essential for neutrophil adhesion.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Antioxidantes/farmacologia , Compostos de Bifenilo/farmacologia , Lignanas , Antígeno de Macrófago 1/fisiologia , Neutrófilos/efeitos dos fármacos , Adulto , Adesão Celular/efeitos dos fármacos , Feminino , Fibrinogênio/fisiologia , Humanos , Peróxido de Hidrogênio/metabolismo , Masculino , Neutrófilos/fisiologia , Superóxidos/metabolismoRESUMO
Possible antiinflammatory effects of dehydroevodiamine (1) and evodiamine (2) were examined by assessing their effects on NO production in the murine macrophage-like cell line RAW 264.7. The results indicated that both 1 and 2 inhibited the IFN-gamma/LPS-stimulated NO production in a concentration-dependent manner. However, 1 appeared to inhibit NO production by interfering not only with the priming signal initiated by IFN-gamma but also with iNOS protein synthesis, while 2 affected the former only.
Assuntos
Alcaloides/farmacologia , Macrófagos/efeitos dos fármacos , Óxido Nítrico/biossíntese , Extratos Vegetais , Quinazolinas/farmacologia , Animais , Células Cultivadas , Interferon gama/farmacologia , Lipopolissacarídeos/farmacologia , Macrófagos/metabolismo , CamundongosRESUMO
A simple and rapid method was applied for direct measurement of nitric oxide (NO) gas produced by cultured macrophages using a modified chemiluminescence detector, the thermal energy analyzer (TEA). HD11 chicken macrophages (1-3 x 10(6)/ml) were cultured on microcarrier beads (100 mg/ml) in 140 ml air-tight glass jars (5 ml cell suspension per jar) containing 0.5 micrograms/ml of LPS and different concentrations of L-arginine. Headspace gas was sampled at 24 hours of culture via a rubber septum and directly injected into a TEA with a liquid nitrogen trap set at -130 to -140 degrees C. The concentration of NO in the gas sample was quantified using a standard gas mixture of NO (2 microliters/L) in nitrogen. Gas samples from L-arginine-supplemented cultures contained NO (0.028-0.066 pl/microliter), whereas NO was not detected in samples from controls. These results suggest that chicken macrophages synthesize NO gas in a dose-dependent manner relative to L-arginine concentration.