消化道肿瘤（GT）主要包括食管癌、胃癌、肝癌、胰腺癌、结直肠癌等，发病率和死亡率均处于较高水平，严重威胁人类健康。刺猬（Hedgehog）信号通路的异常激活参与GT的发生发展、侵袭转移以及免疫逃逸过程，是重要的抗肿瘤靶点。中医药具备多成分、多靶点的优势，在GT防治中展现出重要潜力。目前已有大量基础研究证实，熊果酸、毛兰素、野黄芩苷等中药活性成分，薏苡仁油、半枝莲乙醇提取物等中药提取物，片仔癀、肠复康胶囊、白头翁汤等中药复方可通过调控Hedgehog及其相关信号通路，进而影响肿瘤细胞凋亡、增殖迁移和侵袭、细胞周期、上皮-间质转化、肿瘤干细胞活性、血管生成、肿瘤免疫微环境等生物学过程，共同发挥抗GT作用。系统梳理中医药调控Hedgehog通路抗GT的研究进展，剖析现有研究局限，提出后续可结合多组学、纳米递送技术，开展高质量临床研究，阐释复方配伍的科学内涵，以期为中医药靶向Hedgehog通路治疗GT的机制挖掘、新药研发及临床实践提供参考。

Gastrointestinal tumors (GT), including esophageal cancer, gastric cancer, liver cancer, pancreatic cancer, and colorectal cancer, have high incidence and mortality rates, posing a serious threat to human health. Aberrant activation of the Hedgehog signaling pathway is involved in the initiation, progression, invasion, metastasis, and immune evasion of GT, making it an important anti-tumor target. Traditional Chinese medicine (TCM) offers advantages such as multiple components and multi-target effects, demonstrating significant potential in the prevention and treatment of GT. Numerous basic studies have confirmed that active TCM ingredients—such as ursolic acid, maolanin, and baicalin—as well as extracts like Coicis Semen oil and Scutellaria barbata ethanol extract, and TCM formulas including Pien Tze Huang, Changfukang Capsules, and Baitouweng Decoction—can modulate the Hedgehog pathway and its related signaling cascades, thereby influencing various biological processes including tumor cell apoptosis, proliferation, migration, invasion, cell cycle regulation, epithelial-mesenchymal transition, stem cell activity, angiogenesis, and the tumor immune microenvironment, collectively exerting anti-GT effects. This review systematically summarizes current research on TCM’s regulation of the Hedgehog pathway in combating GT, analyzes existing limitations, and proposes future directions, including integrating multiomics approaches and nanodelivery technologies, conducting high-quality clinical trials, and elucidating the scientific basis of formula synergies. These efforts aim to provide insights for uncovering mechanisms, developing novel therapeutics, and advancing clinical applications of TCM targeting the Hedgehog pathway in GT treatment.

R285.5

国家中医药管理局“张仲景经方合方的临床应用及其作用机制研究项目”（ GZY-KJS-2022-041）；河南省重点研发与推广专项（科技攻关）项目（232102310280）；河南省中医药传承与创新人才工程（仲景工程）中医药学科领军人才项目（豫卫中医函[2021]8号）；河南省中医药科学研究专项课题（2023ZY2071）；河南省卫生健康委员会国家中医临床研究基地项目（2021JDZX2003）