Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing 210009, China.
Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University, Nanjing 210009, China.
Molecules. 2019 Nov 22;24(23):4254. doi: 10.3390/molecules24234254.
In accordance with the provision in , L. (Sour orange-SZS) and Osbeck (Sweet orange-TZS) are all in line with the requirements of (ZS). Both kinds of ZS are also marketed in the market. With the frequent occurrence of depression, Zhi-Zi-Hou-Po decoction (ZZHPD) has attracted wide attention. Currently, studies have shown that ZZHPD has a potential toxicity risk, but the effect of two commercial varieties of ZS on ZZHPD has not been reported. In this study, the toxicity differences of ZZHPD prepared by SZS and TZS were revealed through repeated administration experiments in rats. This indicated that different varieties of ZS could affect the toxicity of the prescription. In order to further study the chemical material basis of the toxicity difference, the fingerprints of ZZHPD prepared by different varieties of ZS were established by high-performance liquid chromatography (HPLC). Five different characteristic peaks were screened by non-target chemometrics. They were identified as geniposide, neoeriocitrin, naringin, hesperidin, and neohesperidin using an HPLC-time-of-flight mass spectrometry analyzer (TOF/MS) and an HPLC-triple stage quadrupole mass spectrometry analyzer (QqQ-MS/MS). Combined with a quantitative analysis and previous studies on promoting the intestinal absorption of geniposide, it is speculated that the synergistic effects of the components may be the main reason for the difference of toxicity among the different medicinal materials. This study provides a reference for the clinical, safe use of ZZHPD, and also provides a new perspective for the study of the potential toxic substances of traditional Chinese medicine compound preparations.
根据规定，酸橙（L.）和甜橙（Osbeck）均符合 ZS 的要求。这两种 ZS 都在市场上销售。随着抑郁症的频繁发生，枳实栀子豉汤（ZZHPD）引起了广泛关注。目前的研究表明，ZZHPD 具有潜在的毒性风险，但尚未报道两种商业品种的 ZS 对 ZZHPD 的影响。在这项研究中，通过大鼠重复给药实验揭示了由 SZS 和 TZS 制备的 ZZHPD 的毒性差异。这表明不同品种的 ZS 可能会影响处方的毒性。为了进一步研究毒性差异的化学物质基础，通过高效液相色谱法（HPLC）建立了由不同品种 ZS 制备的 ZZHPD 的指纹图谱。通过非靶向化学计量学筛选出五个不同的特征峰。使用高效液相色谱-飞行时间质谱分析仪（TOF/MS）和高效液相色谱-三重四极杆质谱分析仪（QqQ-MS/MS）将它们鉴定为京尼平苷、新橙皮苷、柚皮苷、橙皮苷和新橙皮苷。结合定量分析和以前关于促进京尼平苷肠吸收的研究，推测这些成分的协同作用可能是不同药材毒性差异的主要原因。这项研究为 ZZHPD 的临床安全使用提供了参考，也为中药复方制剂潜在毒性物质的研究提供了新的视角。
