Institute of Chinese Traditional Surgery, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.
Department of Liver Disease, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
J Ethnopharmacol. 2018 Oct 5;224:36-44. doi: 10.1016/j.jep.2018.05.031. Epub 2018 May 24.
Wenshen Zhuanggu Formula (WSZG) is a traditional Chinese medicine (TCM) prescription used in clinics for adjuvant treatment of breast cancer bone metastases in Longhua Hospital in China. WSZG has been reported to decrease the risk of bone metastases and alleviate the severity of bone lesions in a breast cancer xenograft model.
The present study aimed at investigating the pharmacokinetic behaviors of six coumarins in normal and breast cancer bone-metastatic mice following oral administration of WSZG extract.
A bone-metastatic mouse model was established by intracardiac injection of MDA-MB-231BO breast cancer cells, and WSZG extract (1.60 g/kg) was given orally to the model and normal mice for 4 weeks. Then, the blood pharmacokinetic parameters of six bioactive components from WSZG (psoralen, isopsoralen, bergapten, xanthotoxin, osthole, and imperatorin) were analyzed by liquid chromatography tandem mass spectrometry.
There were significant differences in pharmacokinetic behaviors between normal and pathological states. Compared with normal mice, the model mice showed significantly increased AUC and AUC of the bioactive compounds (P < 0.05) and significantly decreased total blood clearance (CL/F) (P < 0.05).
The different pharmacokinetic behaviors might be partly ascribed to intestinal functional disorders and imbalance of gastrointestinal microbiota under the morbid state. The findings provide some valuable information to evaluate the clinical efficacy and safety of this TCM formula.
文申壮骨方（WSZG）是一种中药方剂，在中国龙华医院的临床中被用于辅助治疗乳腺癌骨转移。WSZG 已被报道可降低乳腺癌骨转移的风险，并减轻乳腺癌异种移植模型中骨病变的严重程度。
本研究旨在研究口服 WSZG 提取物后正常和乳腺癌骨转移小鼠中六种香豆素的药代动力学行为。
通过心脏内注射 MDA-MB-231BO 乳腺癌细胞建立骨转移小鼠模型，并用 WSZG 提取物（1.60 g/kg）对模型和正常小鼠进行 4 周口服治疗。然后，通过液相色谱串联质谱法分析 WSZG 中六种生物活性成分（补骨脂素、异补骨脂素、佛手柑内酯、花椒毒素、蛇床子素和白芷素）的血药代动力学参数。
正常和病理状态下的药代动力学行为存在显著差异。与正常小鼠相比，模型小鼠的生物活性化合物 AUC 和 AUC 显著增加（P<0.05），总血清除率（CL/F）显著降低（P<0.05）。
不同的药代动力学行为可能部分归因于病态下肠道功能障碍和胃肠道微生物群落失衡。这些发现为评估这种中药方剂的临床疗效和安全性提供了一些有价值的信息。
