Rong Yaojun, Zhang Guiyu, Ye Wenhao, Qi Linhua, Hao Xiaojiang, Li Xiaolin, Zhang Wuhong, Chao Yangfa, Gu Shaodong
Shenzhen Bao'an Traditional Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, China.
The Seventh Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, China.
Cancer Med. 2025 Mar;14(6):e70813. doi: 10.1002/cam4.70813.
Chronic gut inflammation and dysbiosis contribute significantly to colorectal cancer (CRC) development. Shaoyao decoction (SYD) is a well-established Chinese medicine prescription. Besides ameliorating CRC via anti-inflammatory effects, SYD modulates gut microbiota (GM) to improve inflammatory responses in ulcerative colitis (UC). However, whether and how SYD suppresses CRC by regulating GM remains largely unknown.
SD rats were orally administered SYD for 7 days to obtain medicated serum. We utilized liquid chromatography-mass spectrometry (LC-MS) analysis, GeneCards, DisGeNET, and SwissTargetPrediction databases to analyze blank and SYD-medicated rat serum, comparing the findings with those of SYD aqueous extract in previous studies to identify SYD circulating compounds/components with predictable target genes. Using network pharmacology, the potential active compounds and corresponding hub genes associated with modulating GM to suppress CRC were selected for molecular docking. In vivo experiments, a CRC transplantation tumor model was established in BALB/c mice using CT26 cells, with SYD gavage for 14 days. To investigate the mechanism of SYD-regulated GM against CRC, HE and IHC staining, Western blotting, and 16S rRNA sequencing were employed.
LC-MS identified 26 SYD compounds with computationally predicted target genes. Network pharmacology prioritized 13 compounds targeting 8 inflammation/immunity-related genes (IL-17/TNF pathways), validated by molecular docking. In vivo experiments, SYD dose-dependently suppressed tumor growth (p < 0.05, medium/high doses), as confirmed by HE staining and IHC analysis of Ki-67. Notably, SYD potentially delayed CRC liver metastasis and alleviated hepatic injury in tumor-bearing mice. Western blotting demonstrated SYD's inhibition of the IL-17/TNF/NF-κB axis, aligning with computational predictions. 16S rRNA sequencing revealed SYD-enriched Akkermansia and GM structural shifts, mechanistically linking microbiota remodeling to anti-tumor efficacy.
SYD combats CRC via dual modulation of IL-17/TNF/NF-κB signaling and GM ecosystems (e.g., Akkermansia enrichment). This microbiota-immune crosstalk positions SYD as a potential adjunct to conventional therapies, particularly for CRC patients with dysbiosis.
慢性肠道炎症和微生物群失调在结直肠癌（CRC）的发生发展中起重要作用。芍药汤（SYD）是一种成熟的中药方剂。除了通过抗炎作用改善结直肠癌外，芍药汤还可调节肠道微生物群（GM）以改善溃疡性结肠炎（UC）中的炎症反应。然而，芍药汤是否以及如何通过调节肠道微生物群来抑制结直肠癌在很大程度上仍不清楚。
给SD大鼠口服芍药汤7天以获得含药血清。我们利用液相色谱-质谱（LC-MS）分析、GeneCards、DisGeNET和SwissTargetPrediction数据库来分析空白和芍药汤含药大鼠血清，将结果与先前研究中芍药汤水提取物的结果进行比较，以鉴定具有可预测靶基因的芍药汤循环化合物/成分。使用网络药理学，选择与调节肠道微生物群以抑制结直肠癌相关的潜在活性化合物和相应的枢纽基因进行分子对接。在体内实验中，使用CT26细胞在BALB/c小鼠中建立结直肠癌移植瘤模型，用芍药汤灌胃14天。为了研究芍药汤调节肠道微生物群对抗结直肠癌的机制，采用了苏木精-伊红（HE）染色、免疫组化（IHC）、蛋白质印迹法和16S rRNA测序。
LC-MS鉴定出26种具有计算预测靶基因的芍药汤化合物。网络药理学确定了13种靶向8个炎症/免疫相关基因（IL-17/TNF途径）的化合物，并通过分子对接得到验证。在体内实验中，苏木精-伊红染色和Ki-67免疫组化分析证实，芍药汤剂量依赖性地抑制肿瘤生长（p < 0.05，中/高剂量）。值得注意的是，芍药汤可能延迟结直肠癌肝转移并减轻荷瘤小鼠的肝损伤。蛋白质印迹法显示芍药汤对IL-17/TNF/NF-κB轴有抑制作用，与计算预测结果一致。16S rRNA测序显示芍药汤使阿克曼氏菌富集并导致肠道微生物群结构改变，从机制上将微生物群重塑与抗肿瘤疗效联系起来。
芍药汤通过对IL-17/TNF/NF-κB信号和肠道微生物群生态系统（如阿克曼氏菌富集）的双重调节来对抗结直肠癌。这种微生物群-免疫串扰使芍药汤成为传统疗法的潜在辅助药物，特别是对于肠道微生物群失调的结直肠癌患者。
