Effect of curcumin-chitosan microspheres on inflammatory response in ulcerative colitis mice via TLR4/MyD88/NF-κB pathway
10.3760/cma.j.cn121382-20240623-00608
- VernacularTitle:姜黄素壳聚糖微球通过TLR4/MyD88/NF-κB通路对溃疡性结肠炎小鼠炎症反应的影响
- Author:
Zhi QI
1
;
Yongquan YANG
;
Zhihong JIA
Author Information
1. 巴彦淖尔市医院肛肠外科，巴彦淖尔 015000
- Keywords:
Curcumin;
Chitosan;
Microspheres;
Ulcerative colitis;
Toll-like receptor 4;
Myeloid differentiation factor 88;
Nuclear factor-κB
- From:
International Journal of Biomedical Engineering
2024;47(6):568-576
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the effect of curcumin-chitosan microspheres on the inflammatory response in ulcerative colitis (UC) mice via the Toll like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor-κB (NF-κB) pathway.Methods:BALB/c mice were induced to establish a UC model by drinking 5% dextran sulfate sodium (DSS) aqueous solution. According to the random number table method, the mice were randomly divided into model group, empty chitosan microsphere group, curcumin group, curcumin-chitosan microsphere group and curcumin-chitosan microsphere+lipopolysaccharide group, with 12 mice in each group. 0.5% carboxymethyl cellulose solution, 19 mg/ml empty chitosan microsphere solution, 12 mg/ml curcumin solution, 19 mg/ml curcumin-chitosan microsphere solution by gavage, 19 mg/ml curcumin-chitosan microsphere solution by gavage+3 mg/ml lipopolysaccharide solution by intraperitoneal injection were administered at an administration volume of 5 ml/kg. Another 12 BALB/c mice drank purified water were taken as the control group. The disease activity index (DAI) score and colon length of mice in each group were determined. The permeability of the intestinal mucosal barrier of mice in each group was evaluated by detecting the level of fluorescein isothiocyanate (FITC)-labelled dextran. Hematoxylin-eosin (HE) staining was used to detect the pathological morphology of the colon tissue in each group. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of proinflammatory factors [interleukin (IL)-6, tumor necrosis factor-α (TNF-α), IL-1β, IL-18] in serum and colon tissue of mice in each group. The expression levels of TLR4/MyD88/NF-κB pathway related proteins in colon tissues of mice in each group were detected by Western blotting.Results:The DAI score [(0.42±0.49) points] of the curcumin-chitosan microsphere group was lower than that of the model, curcumin, empty chitosan microsphere, and curcumin-chitosan microsphere+lipopolysaccharide groups [(3.50±0.26), (2.33±0.41), (2.83±0.35), and (3.33±0.25) points], and the length of colon [(6.17±0.38) cm] was greater than that of the model, curcumin, empty chitosan microsphere, and curcumin-chitosan microsphere+lipopolysaccharide groups [(3.89±0.23), (5.13±0.34), (4.78±0.31), and (4.01±0.27) cm], and the differences were statistically significant (all P<0.05). The FITC-labelled dextran level in the curcumin-chitosan microsphere group [(2.51±0.70) μg/ml] was lower than that in the model, curcumin, empty chitosan microsphere, and curcumin-chitosan microsphere+lipopolysaccharide groups [(10.13±0.71), (5.47±0.63), (4.52±0.60), (9.63±0.58) μg/ml], and the differences were statistically significant (all P<0.05). The villus height [(160.47±11.34) μm] of the curcumin-chitosan microsphere group was higher than that of the model, curcumin, empty chitosan microsphere, and curcumin-chitosan microsphere+ lipopolysaccharide groups [(102.13±7.65), (134.26±9.42), (124.85±8.36), and (106.94±7.81) μm], the mucosal thickness [(253.89±18.38) μm] was higher than that of the model, curcumin, empty chitosan microsphere, and curcumin-chitosan microsphere+lipopolysaccharide groups [(171.86±12.51), (218.34±13.12), (204.75±14.36), and (175.23±12.74) μm], and the differences were statistically significant (all P<0.05). The serum levels of IL-6, TNF-α, IL-1β, and IL-18 in the curcumin-chitosan microspheres group were (25.58±5.43), (49.37±7.82), (69.85±15.74), and (43.01±7.69) ng/L, respectively, which were lower than those of the model group [(130.69±10.24), (172.14±11.76), (214.54±25.72), and (165.85±18.74) ng/L], the curcumin group [(56.87±6.82), (98.76±10.65), (125.43±18.67), and (94.64±16.85) ng/L], the empty chitosan microspheres group [(68.24±8.67), (113.53±12.13), (149.76±20.35), and (117.93±15.63) ng/L], the curcumin-chitosan microspheres+lipopolysaccharide group [(121.75±9.89), (163.85±10.86), (203.12±24.86), and (154.12±18.54) ng/L], and the differences were statistically significant (all P<0.05). The levels of IL-6, TNF-α, IL-1β, and IL-18 in colon tissue of mice in the curcumin-chitosan microsphere group were (16.94±4.02), (31.12±4.25), (39.13±6.73), and (41.23±7.50) ng/g respectively, which were lower than those of the model group [(92.63±7.21), (114.32±8.24), (142.37±13.41), and (165.85±18.74) ng/g], the curcumin group [(46.86±6.25), (67.95±6.84), (75.20±8.64), and (84.93±11.84) ng/g], and the empty chitosan microsphere group [(57.12±6.73), (79.31±7.76), (89.76±10.52), and (98.74±13.62) ng/g], the curcumin-chitosan microspheres+lipopolysaccharide group [(86.53±7.46), (105.43±7.93), (133.81±12.95), and (154.90±18.39) ng/g], and the differences were statistically significant (all P < 0.05). The relative expression levels of TLR4 and MyD88 proteins and phosphorylated NF-κB p65 (p-NF-κB p65)/NF-κB p65 (0.32±0.07, 0.38±0.09, and 0.09±0.03) in the colon tissue of curcumin-chitosan microspheres group were lower than those of the model group (1.34±0.13, 1.40±0.16, and 0.89±0.09), the curcumin group (0.73±0.09, 0.79±0.11, and 0.39±0.05), the empty chitosan microsphere group (0.82±0.11, 0.89±0.13, and 0.47±0.08), the curcumin-chitosan microsphere+ lipopolysaccharide group (1.31±0.12, 1.36±0.14, and 0.87±0.08), and the differences were statistically significant (all P<0.05). Conclusions:Curcumin-chitosan microspheres can alleviate inflammation, reduce colon tissue damage, and restore intestinal mucosal barrier function in UC mice, which may be achieved by inhibiting TLR4/MyD88/NF-κB signaling activation.
