Inappropriately activated T cells mediate autoimmune diseases and T cell acute lymphoblastic leukemia (T-ALL). Glucocorticoid and chemotherapeutic agents have largely extended lives of these patients. However, serious side effects and drug resistance often limit the prognosis of considerable number of the patients. The efficient treatment of autoimmune diseases or T-ALL with drug resistance remains an important unmet demand clinically. Bisbenzylisoquinoline alkaloids tetrandrine and cepharanthine have been applied for the treatment of certain types of autoimmune diseases and cancers, while studies on their action mechanisms and their further applications combined with glucocorticoids or chemotherapeutic agents remains to be expanded. This review introduced molecular mechanisms of tetrandrine and cepharanthine in T cells, including their therapeutic implications. Both tetrandrine and cepharnthine influence the growth of activated T cells via several kinds of signaling pathways, such as NF-κB, caspase cascades, cell cycle, MAPK, and PI3K/Akt/mTOR. According to recent preclinical and clinical studies, P-glycoprotein inhibitory effect of tetrandrine and cepharnthine could play a significant role on T cell-involved refractory diseases. Therefore, tetrandrine or cepharanthine combined with glucocorticoid or other anti-leukemia drugs would bring a new hope for patients with glucocorticoid-resistant autoimmune disease or refractory T-ALL accompanied with functional P-glycoprotein. In conclusion, bisbenzylisoquinoline alkaloids tetrandrine and cepharanthine can regulate several signaling pathways in abnormally activated T cells with low toxicity. Bisbenzylisoquinoline alkaloids deserve to be paid more attention as a lead compound to develop new drugs for the treatment of T cell-involved diseases in the future.

不适当激活的 T 细胞介导自身免疫性疾病和 T 细胞急性淋巴细胞白血病 (T-ALL)。糖皮质激素和化疗药物在很大程度上延长了这些患者的生命。然而，严重的副作用和耐药性往往限制了相当多患者的预后。有效治疗自身免疫性疾病或具有耐药性的 T-ALL 仍然是临床上未满足的重要需求。双苄基异喹啉生物碱粉防己碱和头孢菌素已用于治疗某些类型的自身免疫性疾病和癌症，但对其作用机制的研究以及与糖皮质激素或化疗药物联合应用的进一步研究仍有待扩展。本综述介绍了粉防己碱和头孢菌素在 T 细胞中的分子机制，包括它们的治疗意义。粉防己碱和头孢氨苄通过多种信号通路影响活化 T 细胞的生长，例如 NF-κB、半胱天冬酶级联、细胞周期、MAPK 和 PI3K/Akt/mTOR。根据最近的临床前和临床研究，粉防己碱和头孢菌素的 P-糖蛋白抑制作用可能对 T 细胞相关的难治性疾病发挥重要作用。因此，粉防己碱或头孢菌素联合糖皮质激素或其他抗白血病药物，将为糖皮质激素抵抗的自身免疫病或伴有功能性P-糖蛋白的难治性T-ALL患者带来新的希望。总之，双苄基异喹啉生物碱粉防己碱和头孢菌素可以调节异常活化的 T 细胞中的几种信号通路，具有低毒性。