[Effect and mechanism of Atractylodis Macrocephalae Rhizoma stir-fried with Aurantii Fructus prepared by Menghe medical school in treating ulcerative colitis].

This study constructed a model of ulcerative colitis(UC) due to spleen deficiency with dampness retention by the method of internal and external factors + trinitrobenzene sulfonic acid(TNBS) and explored the therapeutic effect and mechanism of Atractylodis Macrocephalae Rhizoma stir-fried with Aurantii Fructus prepared by Menghe medical school on UC, aiming to provide a scientific basis for the rational application of this drug in clinical practice. The study was carried out with seven groups: blank, model, positive control, Atractylodis Macrocephalae Rhizoma, Atractylodis Macrocephalae Rhizoma stir-fried with bran, Atractylodis Macrocephalae Rhizoma + Aurantii Fructus, and Atractylodis Macrocephalae Rhizoma stir-fried with Aurantii Fructus. After successful modeling, the positive control group was treated with mesalazine at 0.2 g·kg~(-1), and the other groups with corresponding drugs at 1 g·kg~(-1) for 14 consecutive days. The disease activity index(DAI), colonic epithelial barrier permeability, and colonic pathological changes were evaluated. The protein levels of Claudin-1, Occludin, zonula occludens-1(ZO-1), EPH receptor B2(EPHB2), microtubule-associated protein light chain 3(LC3)-Ⅱ, and ring finger protein 186(RNF186), as well as the mRNA levels of Claudin-1, Occludin, ZO-1, RNF186, and EPHB2, were determined. In addition, the levels of inflammatory cytokines \[interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), interleukin-6(IL-6), and nitric oxide(NO)\] and the ubiquitination level of EPHB2 were measured. Compared with the blank group, the model group showed typical pathological changes of UC, significant increases in DAI score, colon epithelial barrier permeability, and levels of IL-1β, TNF-α, IL-6, and NO in the colon tissue, and significant decreases in the expression of Claudin-1, Occludin, ZO-1, EPHB2, and LC3-Ⅱ. Compared with the model group, Atractylodis Macrocephalae Rhizoma stir-fried with Aurantii Fructus prepared by Menghe medical school ameliorated the pathological characteristics of UC, decreased the DAI score, colon epithelial barrier permeability, and the levels of IL-1β, TNF-α, IL-6, and NO in the colon tissue, and increased the expression of RNF186, Claudin-1, Occludin, ZO-1, EPHB2, and LC3-Ⅱ and the ubiquitization level of EPHB2. In conclusion, Atractylodis Macrocephalae Rhizoma stir-fried with Aurantii Fructus prepared by Menghe medical school could treat UC due to spleen deficiency with dampness retention induced by the method of internal and external factors + TNBS in rats. Specifically, it can up-regulate the expression of RNF186 and modulate EPHB2 ubiquitination to activate intestinal autophagy, repair intestinal epithelial barrier, and relieve intestinal inflammatory damage.