Protective effects of the combination of sodium ferulate and oxymatrine on cecal ligation and puncture-induced sepsis in mice

Abstract

The aim of this study was to investigate the effects of the combination of sodium ferulate (SF) and oxymatrine (OMT) on mice with cecal ligation and puncture (CLP)-induced sepsis. Swiss male mice were randomly divided into a control group, CLP group, three SF + OMT groups (3.1+6.9; 6.2+13.8 and 12.3+27.7 mg/kg), SF (6.2 mg/kg) group and OMT (13.8 mg/kg) group. Eight hours after the administration of the drugs, the survival rates and survival times of the animals were monitored. In addition, the lung wet/dry weight (W/D) ratio; alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) levels in the serum; the C-reactive protein (CRP), interleukin-6 (IL-6) and interferon-γ (IFN-γ) levels in the serum and lung and liver homogenates; and the malondialdehyde (MDA) and superoxidase dismutase (SOD) levels in the lung and liver homogenates were measured. The bacterial load in the serum was also studied. Following treatment with the combination of SF and OMT, the survival rate increased and the survival time was prolonged; CLP-induced increases in the lung W/D ratio and the levels of ALT, AST, LDH, CRP, IL-6, IFN-γ and MDA were significantly reduced; and the SOD activity levels were increased, compared with those of the untreated animals with CLP-induced sepsis. These results indicated that the combination of SF and OMT induced protective effects against CLP-induced lethal sepsis of mice. The possible mechanism of these effects may be associated with the alleviation of systemic inflammation and diminishment of oxidative injury.

Anti-exudation effects of sodium ferulate and oxymatrine combination via modulation of aquaporin 1

“…Treatment with sodium feulate and oxymatrine combination also significantly decreased the leukocyte number as well as the levels of IL-6, CRP and IFN-γ in the peritoneal lavage fluid induced by acetic acid, and its effect was better than that of each drug alone at doses equal to those in the medium combined group, which verified the results of previous studies by our group, which reported that sodium ferulate and oxymatrine combination significantly reduced the levels of IL-6, CRP and IFN-γ in serum or tissue homogenate of other mouse models (5,6,23). IL-6, a pro-inflammatory cytokine, has a vital role in the process of inflammation and macrophage activation (26)(27)(28).…”

“…Previous studies revealed that a combination of sodium ferulate and oxymatrine exerted synergistic anti-inflammatory effects (3)(4)(5)(6). The studies demonstrated that sodium ferulate and oxymatrine combination significantly inhibited xylene-induced edema in mouse ears and carrageenan-induced edema in rat paws.…”

“…In order to investigate the anti-exudation activity of sodium ferulate and oxymatrine combination, the mice were injected with Evans blue and peritonitis was induced with acetic acid according to a previously described method (12). Mice used in the experiment were randomly divided into a normal control group (saline), a model group (saline and acetic acid), 5 Each group contained 10 animals. The animals were intraperitoneally injected with the corresponding drug or drug combination in saline at a volume of 10 ml/kg.…”

“…The studies demonstrated that sodium ferulate and oxymatrine combination significantly inhibited xylene-induced edema in mouse ears and carrageenan-induced edema in rat paws. A mechanistic study revealed that the anti-inflammatory effects of sodium ferulate and oxymatrine combination was mainly associated with its modulatory effect on interleukin-6 (IL-6), IL-11, C-reactive protein (CRP) and interferon-γ (IFN-γ) in a RAW 264.7 cell model stimulated by lipopolysaccharides (4), which had also been verified in mouse models of cecal ligation and puncture-induced sepsis and enthanol-induced liver damage as well as in a RAW 264.7 cell model of lipopolysaccharide-stimulated damage (5,6).…”

“…HUVECs were seeded onto coverslips in a 24-well plate (1x10 5 per well) and incubated in complete medium, containing fresh RPMI-1640 medium supplemented with 10% (v/v) fetal bovine serum at 37˚C under a 5% CO 2 for 24 h. The cells were treated with different concentrations of sodium ferulate (25,50,100,200 or 400 µmol/l in medium) or oxymatrine (50, 100, 200, 400 or 800 µmol/l in medium), or sodium ferulate and oxymatrine combination (25+50, 50+100, 100+200, 200+400 or 400+800 µmol/l in medium), and incubated for 1 h. Acetic acid was then added to the corresponding wells at a concentration of 8 mmol/l. The same amount of solvent was added to the control wells.…”