Betulinic acid（白桦脂酸）是一种天然存在的五环三萜类化合物，广泛存在于白桦树皮、山楂及多种药用植物中^[1]。Betulinic acid（Lupatic acid，AbMole，M3161）通过多种机制调控细胞命运，其核心作用机制包括直接激活线粒体凋亡通路：通过诱导线粒体膜电位丧失、促进细胞色素c释放及caspase-9/3级联激活，选择性诱导肿瘤细胞凋亡而对正常细胞毒性较低^[1]。此外，Betulinic acid（白桦脂酸）还可抑制拓扑异构酶I活性、干扰微管聚合、抑制血管生成及调控NF-κB和STAT3等信号通路^[2]。在细胞实验层面，Betulinic acid在黑色素瘤、神经母细胞瘤、前列腺癌及肺癌等多种肿瘤细胞中可显著诱导细胞凋亡，其EC₅₀值在微摩尔级别；在黑色素瘤细胞中可上调死亡受体CD95的表达，增强TRAIL诱导的凋亡敏感性；在神经母细胞瘤细胞中可抑制神经突生长并诱导细胞分化^[3]。在动物实验层面，Betulinic acid（CAS No.：472-15-1）在小鼠黑色素瘤移植瘤模型中通过腹腔给药可显著抑制肿瘤生长并延长生存期；在神经母细胞瘤模型中可减轻肿瘤负荷并诱导肿瘤细胞分化^[4]。此外，Betulinic acid还被用于研究三萜类化合物在抗炎、抗病毒（如HIV）及动物代谢性疾病中的生物活性^[5]。

参考文献及鸣谢

[1] Pisha, E.; Chai, H.; Lee, I. S.; et al. Discovery of betulinic acid as a selective inhibitor of human melanoma that functions by induction of apoptosis. Nature Medicine 1995, 1 (10), 1046-1051.

[2] Fulda, S. Betulinic acid: a natural product with anticancer activity. Molecular Nutrition & Food Research 2009, 53 (1), 140-146.

[3] Wick, W.; Grimmel, C.; Wagenknecht, B.; et al. Betulinic acid-induced apoptosis in glioma cells: A sequential requirement for new protein synthesis, formation of reactive oxygen species, and caspase processing. Journal of Pharmacology and Experimental Therapeutics 1999, 289 (3), 1306-1312.

[4] Rieber, M. S.; Rieber, M. Signalling responses linked to betulinic acid-induced apoptosis are antagonized by MEK inhibitor U0126 in adherent or 3D spheroid melanoma irrespective of p53 status. International Journal of Cancer 2006, 118 (5), 1135-1143.

[5] Eiznhamer, D. A.; Xu, Z. Q. Betulinic acid: a promising anticancer candidate. IDrugs 2004, 7 (4), 359-373.