Zhejiang University of Technology, No. 18, Chaowang Road, Zhejiang, 310014, Hangzhou, China.
Department of Breast Surgery (Integrated Traditional and Western Medicine), Longhua Hospital, Shanghai University of Traditional Chinese Medicine, No. 725 South Wanping Road, Shanghai, 200032, China.
BMC Complement Altern Med. 2019 Sep 4;19(1):240. doi: 10.1186/s12906-019-2651-0.
Major depression is an important complication in patients with breast cancer, but is an underrecognized and undertreated condition in this population. The Baihe Zhimu Tang (BZ formula) is a traditional Chinese formula consisting of Lilium brownii var. viridulum Baker (L. brownii) and Anemarrhena asphodeloides (A. asphodeloides) Bunge that is used for the treatment of depression. However, the interaction between tamoxifen and BZ formula is frequently overlooked by traditional and alternative medical doctors. In the present study, the influence of BZ formula on the effectiveness of tamoxifen in breast cancer in mice and the effects of tamoxifen on the antidepressant effect of BZ formula and its major components mangiferin and timosaponin BII in mice were investigated.
Identification of the major components of BZ formula was performed using fast HPLC-tandem mass spectrometry (HPLC-MS/MS). The main flavonoids and saponins in A. asphodeloides were determined by HPLC-UV and HPLC-ELSD, separately. The antidepressant efficacy of BZ formula was evaluated using a mouse tail-suspension test. The effects of BZ formula on the antineoplastic activity of tamoxifen were performed in a mouse xenograft model of human breast cancer MCF-7 cells. P450 activity was determined using microsomal incubations by HPLC-MS/MS. Measurement of serum concentrations of tamoxifen and its metabolites was used by HPLC-MS/MS.
BZ formula attenuated the effectiveness of tamoxifen treatment of breast cancer and reduced the concentrations of endoxifen and 4-OH-tamoxifen in tumor-bearing mice. Of two of the major components of BZ formula, the antidepressant effect of mangiferin, but not timosaponin BII, was significantly inhibited by tamoxifen in mice. BZ formula and its component mangiferin also significantly inhibited CYP450 enzyme activity in rat liver microsomes.
BZ formula attenuated the effectiveness of tamoxifen in treatment of breast cancer in mice by influencing CYP450 enzymes. The present study laid a foundation for the treatment of patients with breast cancer and depression by BZ formula or other Chinese herbal formulas containing A. asphodeloides.
重度抑郁症是乳腺癌患者的重要并发症，但在该人群中未得到充分认识和治疗。百合知母汤（BZ 方）是一种由百合（L. brownii）和知母（A. asphodeloides）组成的传统中药方剂，用于治疗抑郁症。然而，传统医学和替代医学医生经常忽略他莫昔芬与 BZ 方之间的相互作用。本研究旨在探讨 BZ 方对乳腺癌小鼠他莫昔芬疗效的影响，以及他莫昔芬对 BZ 方及其主要成分芒果苷和知母皂苷 BII 抗抑郁作用的影响。
采用快速高效液相色谱-串联质谱法（HPLC-MS/MS）鉴定 BZ 方的主要成分。分别采用 HPLC-UV 和 HPLC-ELSD 法测定知母中的主要黄酮类和皂苷类成分。采用小鼠悬尾试验评价 BZ 方的抗抑郁作用。在人乳腺癌 MCF-7 细胞荷瘤小鼠模型中研究 BZ 方对他莫昔芬抗肿瘤活性的影响。采用 HPLC-MS/MS 法测定微粒体孵育物中的细胞色素 P450 活性。采用 HPLC-MS/MS 法测定血清中他莫昔芬及其代谢物的浓度。
BZ 方减弱了他莫昔芬治疗乳腺癌的疗效，并降低了荷瘤小鼠中 Endoxifen 和 4-OH-tamoxifen 的浓度。BZ 方的两种主要成分中，芒果苷的抗抑郁作用，但知母皂苷 BII 的抗抑郁作用，被他莫昔芬在小鼠体内显著抑制。BZ 方及其成分芒果苷也显著抑制大鼠肝微粒体中的 CYP450 酶活性。
BZ 方通过影响 CYP450 酶减弱了他莫昔芬在治疗乳腺癌中的疗效。本研究为 BZ 方或其他含知母的中药方剂治疗乳腺癌合并抑郁症患者奠定了基础。
