抑郁是加速结直肠癌（CRC）进展的重要风险因素之一。通瘀药方（TXYF）是中药治疗与精神相关的肠道疾病的广泛应用的经典配方，它由四种不同的草药组成：白术，白芍药，陈皮和防风。 TXYF拥有百年历史，可以显著改善抑郁情绪并减轻肠道症状。然而，TXYF在伴有心理压力的结直肠癌中的干预效应和机制仍不明确。本研究调查了TXYF对慢性束缚应激（CRS）下的CRC小鼠的治疗效果，并探讨了其机制。我们通过CRS和皮下注射CT26-Luc细胞建立了慢性应激小鼠模型，并通过灌胃给予TXYF。我们测量了每组小鼠的体重、肿瘤体积和肿瘤重量。肿瘤生长通过活体生物荧光分析动态监测。使用悬空试验、强迫游泳试验和激素水平变化评估了每组小鼠的抑郁状态。我们使用流式细胞术检测外周血和肿瘤组织中CD4+ T细胞、CD8+ T细胞、Th1细胞和Th2细胞比例以及树突状细胞（DCs）表型（MHC II、CD80和CD86）和趋化能力（CXCR4和CCR7）。使用ELISA测定了每组小鼠血清中IL-12、IL-18、Th1细胞因子和Th2细胞因子的水平。TXYF可以改善患有CRS的CRC小鼠的体重，抑制肿瘤体积和重量，缓解抑郁状态，升高5-HT水平，抑制HPA轴激素分泌。流式细胞术结果显示，TXYF可以促进DCs表型和功能的成熟，增强抗原呈递能力，增加CD4+ T细胞和CD4+/CD8+ T细胞比例，并使Th1/Th2平衡倾向于Th1细胞，从而增加血清中IFN-γ、IL-18、IL-2和IL-12的水平，降低血清中IL-4和IL-10的水平，并有效引发T细胞介导的免疫应答。本研究表明，TXYF通过刺激免疫应答抑制了患有CRS的CRC小鼠的肿瘤生长。其机制可能通过抑制HPA轴和促进DCs的成熟，从而激活T细胞并增强抗肿瘤免疫应答，最终预防CRC的进展。 版权所有 © 2023 Elsevier B.V. 发表.

Depression is one of the important risk factors that accelerate the progression of colorectal cancer (CRC). Tong-Xie-Yao-Fang (TXYF) is a widely used classical formula for treating psychiatric-related intestinal diseases in traditional Chinese medicine, that is composed of four different herbs: Atractylodes macrocephala Koidz. (Baizhu), Paeonia lactiflora Pall. (Baishaoyao), Citrus reticulata Blanco (Chenpi), Saposhnikovia divaricata (Turcz.) Schischk (Fangfeng). TXYF has over a hundred years of history and can significantly improve depression and reduce intestinal symptoms. However, the intervention effect and mechanism of TXYF on colorectal cancer accompanied by psychological stress are not still clear.This study investigated the therapeutic effect of TXYF on CRC mice with chronic restraint stress (CRS) and to explore its mechanism.We constructed a mouse model of chronic stress by CRS and subcutaneous injection of CT26-Luc cells, and administered TXYF by gavage. We measured the body weight, tumor size, and tumor weight of each group of mice. The tumor growth was monitored dynamically of by vivo bioluminescence analysis. The depressive state of each group of mice were evaluated by tail hanging test, forced swimming test, and hormone level changes. We used flow cytometry to detect the ratio of CD4+ T cells, CD8+ T cells, Th1 cells, Th2 cells, and dendritic cells (DCs) phenotype (MHC II, CD80, and CD86) and chemotaxis ability (CXCR4 and CCR7) of in peripheral blood and tumor tissue. the levels of IL-12, IL-18, Th1 cytokines, and Th2 cytokines in the serum of each group of mice were determined by ELISA.TXYF can improve the body weight of CRC mice with CRS, inhibit tumor volume and weight, alleviate depressive state, upregulate 5-HT levels, and inhibit HPA axis hormone secretion. The results of flow cytometry showed that TXYF can promote the maturation of DCs phenotype and function, enhance antigen presentation ability, increase the ratio of CD4+ T cells and CD4+/CD8+ T cells, and shift Th1/Th2 balance towards Th1 cells, thus increasing serum levels of IFN-γ, IL-18, IL-2, and IL-12, while decreasing serum levels of IL-4 and IL-10, and effectively triggering T cell-mediated immune response.This study shows that TXYF inhibits the growth of tumors in CRC mice with CRS by stimulating immune response. The mechanism may be inhibiting the HPA axis and promoting DCs maturation, thus activating T cells and enhancing anti-tumor immune response, ultimately preventing the progression of CRC.Copyright © 2023. Published by Elsevier B.V.