Department of Food Science and Nutrition, The Hong Kong Polytechnic University, Hong Kong, SAR, China; Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong, SAR, China; Research Center for Chinese Medicine Innovation, The Hong Kong Polytechnic University, Hong Kong, SAR, China.
School of Biological Sciences, The University of Hong Kong, Hong Kong, SAR, China; Department of Microbiology, The University of Hong Kong, and Centre for Virology, Vaccinology and Therapeutics, Hong Kong, SAR, China.
Food Chem. 2025 Jan 15;463(Pt 3):141371. doi: 10.1016/j.foodchem.2024.141371. Epub 2024 Sep 19.
Schisandrin B (Sch B) is a predominant bioactive lignan from the fruit of a Chinese medicine food homology plant, Schisandra chinensis. Previously, we observed potent anti-tumor effect of Sch-B in colorectal cancer (CRC) and enhanced chemotherapy efficacy with fluorouracil (5-FU). However, their bioavailability and reciprocal interactions under CRC conditions are unclear. In this study, we first compared the bioavailability, metabolism and tissue distribution of Sch-B between non-tumor-bearing and xenograft CRC tumor-bearing mice. Next, we examined SchB-5-FU interactions via investigating alterations in drug metabolism and multidrug resistance. Using a validated targeted metabolomics approach, five active metabolites, including Sch-B and fluorodeoxyuridine triphosphate, were found tumor-accumulative. Co-treatment resulted in higher levels of Sch-B and 5-FU metabolites, showing improved phytochemical and drug bioavailability. Multidrug resistance gene (MDR1) was significantly downregulated upon co-treatment. Overall, we demonstrated the potential of Sch-B to serve as a promising chemotherapy adjuvant via improving drug bioavailability and metabolism, and attenuating MDR.
五味子醇 B（Sch B）是中药五味子果实中的一种主要生物活性木质素。先前，我们观察到 Sch-B 在结直肠癌（CRC）中具有很强的抗肿瘤作用，并增强了氟尿嘧啶（5-FU）的化疗效果。然而，它们在 CRC 条件下的生物利用度和相互作用尚不清楚。在这项研究中，我们首先比较了非荷瘤和荷瘤 CRC 荷瘤小鼠之间 Sch-B 的生物利用度、代谢和组织分布。接下来，我们通过研究药物代谢和多药耐药性的改变来检查 SchB-5-FU 的相互作用。使用经过验证的靶向代谢组学方法，发现了五个活性代谢物，包括 Sch-B 和氟脱氧尿苷三磷酸，它们在肿瘤中有蓄积。联合治疗导致 Sch-B 和 5-FU 代谢物水平升高，显示出改善的植物化学物质和药物生物利用度。多药耐药基因（MDR1）在联合治疗时显著下调。总的来说，我们证明了 Sch-B 作为一种有前途的化疗辅助剂的潜力，通过提高药物生物利用度和代谢，并减轻 MDR。
