Luteolin attenuates the pulmonary inflammatory response involves abilities of antioxidation and inhibition of MAPK and NFκB pathways in mice with endotoxin-induced acute lung injury.

Acute lung injury (ALI) in critically ill patients remains the leading cause of mortality and morbidity. Lipopolysaccharide (LPS) is a key mediator of lung injury. This study investigates the protective effects and mechanisms of luteolin in intratracheal instillation of LPS (100µg)-induced ALI in mice. Pretreatment of mice with 70µmol/kg luteolin significantly restores LPS-induced decrease in oxygen pressure and increase in carbon dioxide in arterial blood. The histopathological study established 70µmol/kg luteolin pretreatment markedly attenuates lung histopathological changes, such as haemorrhaging, interstitial edema, and infiltration of polymorphonuclear neutrophils (PMNs) into the lung parenchyma and alveolar spaces. Sufficient evidence for luteolin (35 and 70µmol/kg) suppresses activation and infiltration of PMNs is obtained in expression of surface marker CD11b and Ly6G on cells in bronchoalveolar lavage fluid (BALF) cells and myeloperoxidase activity in lung tissue. Furthermore, luteolin reduces the activity of catalase and superoxide dismutase, and the level of oxidative damage, and lipid peroxidation, in lung tissue. In addition, the secretion of TNF-α, KC, and ICAM-1 in the BALF after LPS challenge are also inhibited by luteolin. Moreover, luteolin reduced LPS-induced activation of MAPK and NFκB pathways. Therefore, luteolin is a potential protective antagonists for LPS-induced ALI in mice.

Protective effects of luteolin against lipopolysaccharide-induced acute lung injury involves inhibition of MEK/ERK and PI3K/Akt pathways in neutrophils.

AIM: To investigate whether luteolin, the major polyphenolic components of Lonicera japonica, has beneficial effects against lipopolysaccharide (LPS)-induced acute lung injury (ALI) and to determine whether the protective mechanism involves anti-inflammatory effects on neutrophils. METHODS: ALI was induced with intratracheal instillation of LPS in mice. The level of ALI was determined by measuring the cell count and protein content in bronchoalveolar lavage (BAL) fluid. Neutrophils were stimulated with formyl-Met-Leu-Phe (fMLP) or LPS in vitro. Chemotaxis and superoxide anion generation were measured to evaluate neutrophil activation. The potential involvement of intracellular signaling molecules in regulating neutrophil activation was analyzed by using Western blot. RESULTS: LPS induced ALI in mice, as evidenced with leukocyte infiltration and protein leakage into the lungs. Luteolin attenuated LPS-induced leukocyte infiltration and protein extravasation. In cell studies, luteolin attenuated the fMLP-induced neutrophil chemotaxis and respiratory burst (IC(50) 0.2+/-0.1 micromol/L and 2.2+/-0.8 micromol/L, respectively), but had a negligible effect on superoxide anion generation during phorbol myristate acetate stimulation. Furthermore luteolin effectively blocked MAPK/ERK kinase 1/2 (MEK), extracellular signal-regulated kinase (ERK), and Akt phosphorylation in fMLP- and LPS-stimulated neutrophils. CONCLUSION: These results indicate that luteolin has beneficial effects against LPS-induced ALI in mice, and the attenuation of neutrophil chemotaxis and respiratory burst by luteolin involves the blockade of MEK-, ERK-, and Akt-related signaling cascades.

The short-/intermediate-term changes in novel vascular inflammatory markers after angioplasty plus stenting in patients with symptomatic advanced systemic arterial diseases.

Studies on cell adhesion molecules and high-sensitivity C-reactive protein (hs-CRP) in systemic arterial diseases are limited in numbers and some results not consistent. It also remains undefined whether, for how long and to what extent these markers are perturbed after angioplasty. Patients with systemic arterial diseases admitted for percutaneous transluminal angioplasty (PTA) by standard procedures and techniques were prospectively studied. Fasting morning blood samples were collected to determine general biochemistry and relevant molecules by commercially available methods at baseline, 2 weeks and 3 months post-PTA/stenting. A group of equally numbered sex- and age-matched asymptomatic subjects without illness were selected as control. A total of 33 patients (28 M/5 F, aged 72 +/- 2 years) were recruited. Patients with systemic arterial disease had significantly higher baseline serum creatinine, circulating VCAM-1, ICAM-1, and hs-CRP, but lower p-selectin and HDL-C than control subjects. Except ICAM-1, cell adhesion molecules and hs-CRP levels were aroused significantly for at least 2 weeks after PTA/stenting, returned to baseline by 3 months, but p-selectin remained elevated beyond 3 months. ICAM-1 only showed a modest rise after PTA but the overall change was insignificant. In conclusion, cell adhesion molecules and hs-CRP did play a significant role in patients with advanced systemic arterial diseases who underwent PTA/stenting.