Department of General Surgery, Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, 215009, China.
School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
Chin J Integr Med. 2024 Jul;30(7):623-632. doi: 10.1007/s11655-023-3552-0. Epub 2023 May 24.
To clarify the potential mechanism of Banxia Xiexin Decoction (BXD) on colorectal cancer (CRC) from the perspective of metabolomics.
Forty male C57BL/6 mice were randomly divided into normal control (NC), azoxymethane/dextran sulfate sodium (AOM/DSS) model, low-dose BXD (L-BXD), high-dose BXD (H-BXD) and mesalamine (MS) groups according to a random number table, 8 mice in each group. Colorectal cancer model was induced by AOM/DSS. BXD was administered daily at doses of 3.915 (L-BXD) and 15.66 g/kg (H-BXD) by gavage for consecutive 21 days, and 100 mg/kg MS was used as positive control. Following the entire modeling cycle, colon length of mice was measured and quantity of colorectal tumors were counted. The spleen and thymus index were determined by calculating the spleen/thymus weight to body weight. Inflammatory cytokine and changes of serum metabolites were analyzed by enzyme-linked immunosorbent assay kits and ultra performance liquid chromatography-quadrupole/time-of-flight mass spectrometry (UPLC-Q/TOF-MS), respectively.
Notably, BXD supplementation protected against weight loss, mitigated tumor formation, and diminished histologic damage in mice treated with AOM/DSS (P<0.05 or P<0.01). Moreover, BXD suppressed expression of serum inflammatory enzymes, and improved the spleen and thymus index (P<0.05). Compared with the normal group, 102 kinds of differential metabolites were screened in the AOM/DSS group, including 48 potential biomarkers, involving 18 main metabolic pathways. Totally 18 potential biomarkers related to CRC were identified, and the anti-CRC mechanism of BXD was closely related to D-glutamine and D-glutamate metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, arginine biosynthesis, nitrogen metabolism and so on.
BXD exerts partial protective effects on AOM/DSS-induced CRC by reducing inflammation, protecting organism immunity ability, and regulating amino acid metabolism.
从代谢组学角度阐明半夏泻心汤（BXD）治疗结直肠癌（CRC）的潜在机制。
40 只雄性 C57BL/6 小鼠按随机数字表法分为正常对照组（NC）、氧化偶氮甲烷/葡聚糖硫酸钠（AOM/DSS）模型组、低剂量 BXD（L-BXD）组、高剂量 BXD（H-BXD）组和 5-氨基水杨酸（MS）组，每组 8 只。采用 AOM/DSS 诱导 CRC 模型，BXD 按 3.915（L-BXD）和 15.66 g/kg（H-BXD）剂量灌胃给药，连续 21 天，MS 按 100 mg/kg 作为阳性对照。完成整个建模周期后，测量小鼠的结肠长度并计数结直肠肿瘤数量。通过计算脾/胸腺重量与体重的比值来确定脾/胸腺指数。采用酶联免疫吸附试剂盒和超高效液相色谱-四极杆/飞行时间质谱（UPLC-Q/TOF-MS）分别分析炎性细胞因子和血清代谢物的变化。
BXD 补充剂可预防 AOM/DSS 处理的小鼠体重减轻、肿瘤形成减少和组织学损伤减轻（P<0.05 或 P<0.01）。此外，BXD 抑制了血清炎性酶的表达，改善了脾/胸腺指数（P<0.05）。与正常组相比，AOM/DSS 组筛选出 102 种差异代谢物，包括 48 种潜在生物标志物，涉及 18 条主要代谢途径。共鉴定出 18 种与 CRC 相关的潜在生物标志物，BXD 的抗 CRC 机制与 D-谷氨酰胺和 D-谷氨酸代谢、苯丙氨酸、酪氨酸和色氨酸生物合成、精氨酸生物合成、氮代谢等密切相关。
BXD 通过减少炎症、保护机体免疫能力和调节氨基酸代谢，对 AOM/DSS 诱导的 CRC 发挥部分保护作用。
