Li Tiegang, Yan Zheng, Zhou Mingxuan, Zhao Wenyi, Zhang Fang, Lv Silin, Hou Yufang, Zeng Zifan, Yang Liu, Zhou Yixin, Zhu Zengni, Ren Xinyi, Yang Min
State Key Laboratory of Digestive Health, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Pharmaceuticals (Basel). 2025 Jul 17;18(7):1052. doi: 10.3390/ph18071052.
Huang Qin Decoction (HQD) is a well-established Traditional Chinese Medicine (TCM) formulation recognized for its application in the treatment of colorectal cancer (CRC). However, the precise therapeutic mechanisms remain inadequately defined. This study integrates metabolomics from a mouse model and network pharmacology to screen potential targets and bio-active ingredients of HQD. The pharmacological activity of HQD for CRC was evidenced via single-cell RNA sequencing (scRNA-seq), molecular docking, and molecular dynamics simulations. Atomic force microscopy (AFM) assays and cellular experimental validation were used to confirm the relative mechanisms. The metabolite profile undergoes significant alterations, with metabolic reprogramming evident during the malignant progression of CRC liver metastasis. Network pharmacology analysis identified that HQD regulates several metabolic pathways, including arginine biosynthesis, alanine, aspartate, and glutamate metabolism, nitrogen metabolism, phenylalanine metabolism, and linoleic acid metabolism, by targeting key proteins such as aspartate aminotransferase (GOT1), cytochrome P450 1A2 (CYP1A2), and carbonic anhydrase 2 (CA2). ScRNA-seq analysis indicated that HQD may enhance the functionality of cytotoxic T cells, thereby reversing the immunosuppressive microenvironment. Virtual verification revealed a strong binding affinity between the identified hub targets and active constituents of HQD, a finding subsequently corroborated by AFM assays. Cellular experiments confirmed that naringenin treatment inhibits the proliferation, migration, and invasion of CRC cells by downregulating GOT1 expression and disrupting glutamine metabolism. Computational prediction and validation reveal the active ingredients, potential targets, and molecular mechanisms of HQD against CRC liver metastasis, thereby providing a scientific foundation for the application of TCM in CRC treatment.
黄芩汤（HQD）是一种成熟的中药配方，因其在治疗结直肠癌（CRC）方面的应用而受到认可。然而，其确切的治疗机制仍未得到充分阐明。本研究整合了小鼠模型的代谢组学和网络药理学，以筛选HQD的潜在靶点和生物活性成分。通过单细胞RNA测序（scRNA-seq）、分子对接和分子动力学模拟，证实了HQD对CRC的药理活性。采用原子力显微镜（AFM）检测和细胞实验验证来确认相关机制。在CRC肝转移的恶性进展过程中，代谢物谱发生了显著变化，代谢重编程明显。网络药理学分析表明，HQD通过靶向关键蛋白，如天冬氨酸转氨酶（GOT1）、细胞色素P450 1A2（CYP1A2）和碳酸酐酶2（CA2），调节多种代谢途径，包括精氨酸生物合成、丙氨酸、天冬氨酸和谷氨酸代谢、氮代谢、苯丙氨酸代谢和亚油酸代谢。scRNA-seq分析表明，HQD可能增强细胞毒性T细胞的功能，从而逆转免疫抑制微环境。虚拟验证显示，所确定的枢纽靶点与HQD的活性成分之间具有很强的结合亲和力，这一发现随后得到AFM检测的证实。细胞实验证实，柚皮素处理通过下调GOT1表达和破坏谷氨酰胺代谢来抑制CRC细胞的增殖、迁移和侵袭。计算预测和验证揭示了HQD抗CRC肝转移的活性成分、潜在靶点和分子机制，从而为中药在CRC治疗中的应用提供了科学依据。
