Effect of ferulic acid on pulmonary function in mice with chronic obstructive pulmonary disease and its mechanism / 中国中西医结合急救杂志

ABSTRACT

Objective To investigate the protective effect of ferulic acid on lung function in mice with chronic obstructive pulmonary disease (COPD) and its possible mechanism. Methods Sixty mice were randomly divided into normal control group, COPD model group, Rofloast group and ferulic acid high, medium and low dose groups, each group with 10 rats, and during administration one rat died in the mode group and was eliminated. The COPD model was duplicated by smoking method; the mice in normal control group were fed normally without any treatment. After modeling for 30 days, normal saline begun to be given to the COPD model group and normal control group; the mice in Rofluast group were given Rofluast 65 μg/kg; ferulic acid 160, 80, 40 mg/kg were given to high, middle and low dose groups respectively. The indexes were determined after consecutive 90 days of treatment, the changes of peak inspiratory flow (PIF) rate, peak expiratory flow (PEF) rate and ventilation volume per minute (MV), mean lining interval (MLI), alveolar destruction index (DI), interleukin-6 (IL-6) and tumor necrosis factor-α(TNF-α) levels in serum and bronchoalveolar lavage fluid (BALF), the protein expressions and phosphorylation levels of p38 mitogen-activated protein kinases (p38MAPK), extracellular signal-regulated kinase (ERK) and c-Jun amino terminal kinase (JNK) in the pulmonary tissue MAPK signaling pathway were observed in each mouse of various mice groups. Results In the COPD model group, the PIF, PEF, and MV were all significantly lower than those in the normal control group [PIF (mL/s) 2.32±0.18 vs. 3.41±0.12, PEF (mL/s) 2.31±0.22 vs. 2.90±0.15, MV (mL/s) 26.20±2.70 vs. 35.18±2.30); Luofusite and all doses of ferulic acid can increase PIF, PEF, and MV, and the degree of increase in the high dose ferulic acid group was more significant than those in the moderate and low dose ferulic acid groups [PIF (mL/s) 3.24±0.13 vs. 2.88±0.15, 2.51±0.10, PEF (mL/s) 2.81±0.16 vs. 2.66±0.11, 2.58±0.17, MV (mL/s)31.18±1.20 vs. 28.25±2.20, 27.09±1.10]; however, there was no statistical significant difference between the Rofluas group and the ferulic acid groups (all P > 0.05). The levels of the MLI, DI, and inflammatory factors in serum and BALF, and the protein expressions and phosphorylation levels of p38MAPK, ERK, JNK in lung tissue in model group were all significantly higher than those in normal control group [MLI (μm) 52.10±0.26 vs. 21.90±0.14, DI (60.78±3.32)% vs. (22.47±1.05)%, IL-6 in serum (ng/L) 22.34±4.51 vs. 3.50±1.55, TNF-αin serum (ng/L) 27.11±3.99 vs. 4.66±1.76, IL-6 (ng/L) in BALF 142.92±20.10 vs. 18.77±4.17, TNF-α(ng/L) 150.16±20.77 vs. 22.01±4.15, P-ERK/ERK (gray value) 0.59±0.03 vs. 0.38±0.05, P-p38MAPK/p38MAPK (gray value) 0.52±0.02 vs. 0.31±0.05, P-JNK/JNK (gray value) 0.56±0.03 vs. 0.25±0.01, all P < 0.05]. The levels of MLI, DI, and inflammatory factors in serum and BALF, p38MAPK, ERK, JNK protein expression and phosphorylation in lung tissue were reduced by Rofluas and various doses of ferulic acid, the reduction levels in the high dose group of ferulic acid were more significant than those in the middle and low dose groups of ferulic acid [MLI (μm) 25.00±0.19 vs. 30.10±0.29, 38.80±0.41, DI (26.32±3.05)% vs. (29.75±6.17)%, (40.56±5.81)%, IL-6 in serum (ng/L) 9.20±1.87 vs. 12.35±2.16, 18.95±3.12, TNF-α(ng/L) 13.37±2.73 vs. 18.02±2.62, 21.31±3.75, IL-6 (ng/L) in BALF 64.27±11.72 vs. 99.33±13.02, 120.31±18.02, TNF-α(ng/L) 58.20±10.28 vs. 93.83±16.26, 122.68±14.85, P-ERK/ERK (gray value) 0.43±0.04 vs. 0.46±0.04, 0.52±0.02, P-p38MAPK/p38MAPK (gray value) 0.33±0.03 vs. 0.34±0.03, 0.38±0.02, P-JNK/JNK (gray value) 0.32±0.04 vs. 0.38±0.05, 0.47±0.06). The ferulic acid could improve the inflammatory cell infiltration situation in mice with COPD. Conclusions Ferulic acid can improve pulmonary inflammation in COPD rats. The effective mechanism is possibly related to the inhibition of the protein expressions and phosphorylation levels of the key proteins such as p38MAPK, ERK and JNK in the MAPK signaling pathway.