Research Progress on the Pharmacological Effects and Antitumor Activity of 4-Methoxydalbergione

4-甲氧基黄檀醌(4-Methoxydalbergione, 4-MD)是从黄檀属植物心材中分离得到的一种天然黄酮类化合物，在黄檀醌类成分中分布最广。现代研究表明，4-MD具有抗炎、抗过敏及广谱的抗肿瘤活性。其可通过调控JAK2/STAT3、NF-κB、PI3K/AKT、MAPK/ERK等多种信号通路，抑制骨肉瘤、神经胶质瘤、神经母细胞瘤、肝癌、肺癌、食管癌、膀胱癌等多种恶性肿瘤的进展。其抗肿瘤机制涉及直接抑制肿瘤细胞增殖、迁移，诱导细胞凋亡、自噬及铁死亡，并可通过抗炎作用改善肿瘤微环境。此外，4-MD还表现出抗疟原虫、抗利什曼原虫、抑制脲酶及诱导醌还原酶等活性。本文系统综述了4-MD的化学结构特征、药理作用及其在不同肿瘤中的作用与分子机制，并对当前研究的局限与未来临床应用方向进行探讨，以期为推动其进一步研究与临床转化提供理论依据。4-Methoxydalbergione (4-MD) is a naturally occurring flavonoid compound isolated from the heartwood of Dalbergia species, and it is the most widely distributed constituent among the dalbergione-type compounds. Modern pharmacological studies have demonstrated that 4-MD possesses anti-inflammatory, anti-allergic, and broad-spectrum antitumor activities. It exerts its effects by modulating multiple signaling pathways, including JAK2/STAT3, NF-κB, PI3K/AKT, and MAPK/ERK, thereby suppressing the progression of various malignancies, such as osteosarcoma, glioma, neuroblastoma, hepatocellular carcinoma, lung cancer, esophageal cancer, and bladder cancer. The underlying antitumor mechanisms involve direct inhibition of tumor cell proliferation and migration, induction of apoptosis, autophagy, and ferroptosis, as well as improvement of the tumor microenvironment through anti-inflammatory actions. In addition, 4-MD exhibits antimalarial and antileishmanial activities, inhibits urease, and induces quinone reductase. This review systematically summarizes the chemical structural characteristics, pharmacological effects, and molecular mechanisms of 4-MD in different tumor types, while also discussing current research limitations and future directions for clinical application, aiming to provide a theoretical foundation for further investigation and translational development.