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仙莲解毒汤通过调节代谢谱、肠道微生物群和代谢物来缓解结直肠癌。

Xianlian Jiedu Decoction alleviates colorectal cancer by regulating metabolic profiles, intestinal microbiota and metabolites.

机构信息

Jiangsu Key Laboratory for High Technology Research of TCM Formulae, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing 210023, PR China.

The First Clinical Medical College of Nanjing University of Chinese Medicine Collaborative Innovation Center of Traditional Chinese Medicine Prevention and Treatment of Tumor, Nanjing University of Chinese Medicine, Nanjing 210023, PR China.

出版信息

Phytomedicine. 2024 Jun;128:155385. doi: 10.1016/j.phymed.2024.155385. Epub 2024 Jan 27.

DOI:10.1016/j.phymed.2024.155385
PMID:38569292
Abstract

BACKGROUND

Xianlian Jiedu Decoction (XLJDD) has been used for the treatment of colorectal cancer (CRC) for several decades because of the prominent efficacy of the prescription. Despite the clear clinical efficacy of XLJDD, the anti-CRC mechanism of action is still unclear.

PURPOSE

The inhibitory effect and mechanism of XLJDD on CRC were investigated in the azoxymethane/dextran sulfate sodium (AOM/DSS)-induced mice.

METHODS

The AOM/DSS-induced mice model was adopted to evaluate the efficacy after administering the different doses of XLJDD. The therapeutic effects of XLJDD in treating AOM/DSS-induced CRC were investigated through histopathology, immunofluorescence and ELISA analysis methods. In addition, metabolomics profile and 16S rRNA analysis were used to explore the effective mechanisms of XLJDD on CRC.

RESULTS

The results stated that the XLJDD reduced the number of tumor growth on the inner wall of the colon and the colorectal weight/length ratio, and suppressed the disease activity index (DAI) score, meanwhile XLJDD also increased body weight, colorectal length, and overall survival rate. The treatment of XLJDD also exhibited the ability to lower the level of inflammatory cytokines in serum and reduce the expression levels of β-catenin, COX-2, and iNOS protein in colorectal tissue. The findings suggested that XLJDD has anti-inflammatory properties and may provide relief for those suffering from inflammation-related conditions. Mechanistically, XLJDD improved gut microbiota dysbiosis and associated metabolic levels of short chain fatty acids (SCFAs), sphingolipid, and glycerophospholipid. This was achieved by reducing the abundance of Turicibacter, Clostridium_sensu_stricto_1, and the levels of sphinganine, LPCs, and PCs. Additionally, XLJDD increased the abundance of Enterorhabdus and Alistipes probiotics, as well as the content of butyric acid and isovaleric acid.

CONCLUSION

The data presented in this article demonstrated that XLJDD can effectively inhibit the occurrence of colon inner wall tumors by reducing the level of inflammation and alleviating intestinal microbial flora imbalance and metabolic disorders. It provides a scientific basis for clinical prevention and treatment of CRC.

摘要

背景

仙连解毒汤(XLJDD)因其处方疗效显著,已被用于治疗结直肠癌(CRC)数十年。尽管 XLJDD 具有明确的临床疗效,但作用机制仍不清楚。

目的

研究 XLJDD 对氧化偶氮甲烷/葡聚糖硫酸钠(AOM/DSS)诱导的小鼠 CRC 的抑制作用及机制。

方法

采用 AOM/DSS 诱导的小鼠模型,评价不同剂量 XLJDD 给药后的疗效。通过组织病理学、免疫荧光和 ELISA 分析方法研究 XLJDD 治疗 AOM/DSS 诱导的 CRC 的疗效。此外,代谢组学分析和 16S rRNA 分析用于探讨 XLJDD 对 CRC 的有效作用机制。

结果

结果表明,XLJDD 减少了结肠内壁肿瘤的数量和结直肠重量/长度比,并抑制了疾病活动指数(DAI)评分,同时 XLJDD 还增加了体重、结肠长度和总生存率。XLJDD 的治疗还表现出降低血清中炎症细胞因子水平和降低结肠组织中β-catenin、COX-2 和 iNOS 蛋白表达水平的能力。结果表明,XLJDD 具有抗炎作用,可能为炎症相关疾病患者提供缓解。在机制上,XLJDD 改善了肠道微生物失调和相关的短链脂肪酸(SCFAs)、神经酰胺、甘油磷脂代谢水平。这是通过降低 Turicibacter、Clostridium_sensu_stricto_1 的丰度和神经酰胺、LPCs、PCs 的水平来实现的。此外,XLJDD 增加了 Enterorhabdus 和 Alistipes 益生菌的丰度以及丁酸和异戊酸的含量。

结论

本文数据表明,XLJDD 通过降低炎症水平、缓解肠道微生物菌群失衡和代谢紊乱,可有效抑制结肠内壁肿瘤的发生,为 CRC 的临床防治提供了科学依据。

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