In order to develop a novel strategy to alleviate the inherent hepatotoxicity of antidepressant trazodone (TZ), Cucurbit[7]uril (CB[7]) was adopted as pharmaceutical excipients and was studied for its capability to reduce the hepatotoxicity of TZ via supramolecular encapsulation. CB[7] was found to form strong 1:1 host-guest complexes with TZ and its metabolite m-chlorophenyl piperazine (mCPP), with binding constants of 1.50 (±0.13) × 10⁶ M⁻¹ and 6.90 (±0.49) × 10⁵ M⁻¹, respectively. The supramolecular complexations were examined by ¹H NMR and UV-visible spectroscopic titrations, ESI-MS and ITC. In the presence of 0.5 mM CB[7], the IC₅₀ values of TZ and mCPP on a human normal liver cell line L02 were increased from 215.5 ± 3.3 μM to 544.1 ± 51.2 μM, and from 166.8 ± 3.8 μM to 241.7 ± 6.8 μM, respectively. Evaluation on a zebrafish model demonstrated that CB[7] (0.1 mM) significantly alleviated the TZ induced liver toxicity, as shown by the level of liver degeneration, liver size and yolk sac retention. Our study may provide a supramolecular strategy to alleviate the hepatotoxicity induced by TZ and its metabolite mCPP, and this strategy may be extendable to other drugs that have inherent hepatotoxicity or other adverse effects.

为了开发减轻抗抑郁剂曲唑酮（TZ）固有肝毒性的新策略，采用了葫芦[7] uril（CB [7]）作为药物赋形剂，并研究了其通过超分子包封降低TZ肝毒性的能力。 。CB [7]被发现，形成强1:1主-客体复合物与TZ及其代谢物米-氯苯基哌嗪（mCPP的）中，用1.50结合常数（±0.13）×10 ⁶ 中号^-1和6.90（±0.49） ×10 ⁵  M ^-1。超分子络合物通过¹ H NMR和UV-可见光谱滴定，ESI-MS和ITC进行检查。在存在0.5 mM CB [7]的情况下，IC ₅₀人类正常肝细胞L02上的TZ和mCPP值分别从215.5±3.3μM增加到544.1±51.2μM和从166.8±3.8μM增加到241.7±6.8μM。对斑马鱼模型的评估表明，CB [7]（0.1 mM）显着减轻了TZ诱导的肝毒性，如肝变性水平，肝大小和卵黄囊retention留所显示。我们的研究可能提供减轻TZ及其代谢产物mCPP诱导的肝毒性的超分子策略，并且该策略可能扩展到具有固有肝毒性或其他不良作用的其他药物。