Objective To investigate the effect of Pueraria lobata extract on intestinal mucosal injury via p38 mitogen-activated protein kinase (p38 MAPK)-peroxidase proliferator-activated receptor-γ (PPARγ)-nuclear factor-κB (NF-κB) regulation pathway in rats with ulcerative colitis (UC).
Methods UC model was established in 75 specific pathogen free Sprague-Dawley (SD) rats and a control group in another 15 rats. The UC model rats were assigned into a model group (gavaged with saline) and low, moderate, high Pueraria lobata extract (gavaged at dosages of 1.75, 3.5, and 5.25 g/kg) groups, and a senescence-associated secretory phenotype (SASP) (0.3 g/kg) group; the gavages were performed once a day continuously for 14 days. General condition of all the rats were observed during the experiment. At the end of the treatments, all the rats were weighed; the disease activity index (DAI), colon mucosal damage index (CMDI), and histological damage index (HDI) were determined; serum interleukin-1β (IL-1β), interleukin-4 (IL-4), and interleukin-6 (IL-6) were detected by enzyme-linked immunosorbent assay (ELISA); the expressions of p38 mitogen-activated protein kinase (p38 MAPK), peroxidase proliferator-activated receptor-γ (PPARγ), and nuclear factor-κB (NF-κB) were detected with quantitative reverse-transcription PCR (qRT-PCR); Western blot was used to detect the expression of protein in colon tissues.
Results In the rats of model group, anorexia, lethargy, and purulent stool were observed and weight gain decreased but DAI score increased in comparison with those of the control rats (P < 0.05). Alleviated pathological symptoms were observed and weight gain increased but DAI score declined significantly in the rats one week after Pueraria lobata extract and SASP treatment (P < 0.05). No pathological changes were observed in the rats of control group; while there were edema, hemorrhage, and scattered ulcer in colon tissues of model rats and microscopic observations of (hematoxylin-eosin) HE staining specimens revealed necrosis and exfoliation of epithelial cells and infiltration of inflammatory cells in colon tissues of the model rats; both gross anatomic and microscopic observations indicated obviously alleviated pathological changes in colon tissues of the rats treated with Pueraria lobata extract and SASP compared to the model rats. The model rats showed significantly higher CMDI and DAI than those of the control rats (both P < 0.05) but the CMDI and DAI of the rats treated with Pueraria lobata extract and SASP were significantly lower than those of model rats (both P < 0.05). Significantly increased IL-6 and IL-1β but decreased IL-4 were detected in the rats of model group compared to those of the control rats (P < 0.05 for all); compared to the model rats, the rats with Pueraria lobata extract and SASP had significantly decreased IL-6 and IL-1β but increased IL-4 (both P < 0.05). Compared to the control rats, the model rats had significantly increased protein and mRNA expressions of p38 MAPK and NF-κB and decreased protein and mRNA expression of PPARγ in colon tissues (all P < 0.05); while the protein and mRNA expressions of p38 MAPK and NF-κB decreased but the protein and mRNA expression of PPARγ increased significantly in colon tissues of the rats with Pueraria lobata extract and SASP treatment in comparison with those in the model rats (P < 0.05 for all).
Conclusion Pueraria lobata extract can improve the survival of UC model rats and play a protective role in intestinal mucosa by down-regulating p38 MAPK, NF-κBp65 and up-regulating PPARγ protein expression.
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