Protective effect of Chrysanthemum morifolium Ramat. ethanol extract on lipopolysaccharide induced acute lung injury in mice

Abstract

Background: To evaluate the effect of Chrysanthemum morifolium Ramat. ethanol extract (CEE) on lipopolysaccharide induced acute lung injury in mice.

Methods: The ninety C57BL/6 J male mice randomly divided into five groups: control, model and CEE (50, 100, 200 mg/kg) groups for 7 days oral administration. At the last administration, all mice except control were intratracheal instilled with lipopolysaccharide (LPS, 3 mg/kg) for establish the acute lung injury. Then lung histopathologic, lung wet/dry weight, white blood cells, lymphocytes, neutrophils were detected. The pro-inflammation cytokine tumor necrosis factor-α (TNF-α), interleukin (IL)-6, anti-inflammatory cytokine transforming growth factor-β1 (TGF-β1), IL-10 and the marker of antioxides ability total-antioxidant capacity (T-AOC), malondialdehyde (MDA) in lung tissue were measured.

Results: The result showed that CEE could improve lung histopathological injury, reduce the ratio of wet/dry lung weight and lung index, inhibit the increased number of white blood cells, lymphocytes and neutrophils, and reduce the increased levels of TNF-α and IL-6. While CEE also significantly increased the levels of TGF-β1 and IL-10. Furthermore, CEE also markedly increased the activity of T-AOC, and decreased the contents of MDA with a dose-dependent manner.

Conclusions: The study exhibited that CEE has a potential protective effect on lipopolysaccharide induced acute lung injury in mice, the action mechanism of CEE may through balance of the pro-inflammatory and anti-inflammatory factors, and the oxygen free radicals inhibition.

Keywords: Acute lung injury; Chrysanthemum morifolium Ramat. ethanol extract; Lipopolysaccharide; Total flavonoids; Total triterpenoids.

Fig. 1

Effect of CEE on white blood cells in BALF of ALI mice (n = 18). ^##P < 0.01 vs normal group, ^*P < 0.05, ^**P < 0.01 vs model group. CEE: Chrysanthemum morifolium Ramat. ethanol extract; ALI: acute lung injury

Fig. 2

Effect of CEE on lung wet/dry weight ratio, lung index and lung dry/body weight ratio in ALI mice (n = 18). ^##P < 0.01 vs normal group, ^*P < 0.05, ^**P < 0.01 vs model group. CEE: Chrysanthemum morifolium Ramat. ethanol extract; ALI: acute lung injury

Fig. 3

Effect of CEE on lung histopathology in ALI mice (H&E, Scale bar 50 μm). a. vehicle group, b. LPS model group, c. CEE 10 mg/kg, d. CEE 30 mg/kg e. CEE 60 mg/kg. f. the statistical data of the inflammation areas in each group. CEE: Chrysanthemum morifolium Ramat. ethanol extract; ALI, acute lung injury

Fig. 4

Effect of CEE on the levels of TGF-β1 and IL-10 in lung tissue of ALI mice (n = 18). ^##P < 0.01 vs normal group, ^*P < 0.05, ^**P < 0.01 vs model group. CEE: Chrysanthemum morifolium Ramat. ethanol extract; ALI, acute lung injury

Fig. 5

Bioactive constitutes of CEE. a. the HPLC chromatograph of the standard compounds 1–12. b. the HPLC chromatograph of CEE. c. the chemical structures of compounds 1–12: Neochlorogenic acid (1), chlorogenic acid (2), caffeic acid (3), 1,3-dicaffeoylquinic acids (4), cynaroside (5), isochlorogenic acid C (6), isochlorogenic acid A (7), isochlorogenic acid B (8), linarin (9), luteolin (10), apigenin (11) and acacetin (12)