The Effects of Different Varieties of Aurantii Fructus Immaturus on the Potential Toxicity of Zhi-Zi-Hou-Po Decoction Based on Spectrum-Toxicity Correlation Analysis.

Qianqian Zhang,Fang Feng

doi:10.3390/molecules24234254

Qianqian Zhang, Fang Feng

Open Access

https://doi.org/10.3390/molecules24234254

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Journal: Molecules (Basel, Switzerland)	Publication Date: Nov 22, 2019
Citations: 14	License type: CC BY 4.0

Affiliation: China Pharmaceutical University

Abstract

In accordance with the provision in China Pharmacopoeia, Citrus aurantium L. (Sour orange—SZS) and Citrus sinensis Osbeck (Sweet orange—TZS) are all in line with the requirements of Aurantii Fructus Immaturus (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.

Highlights

Aurantii Fructus Immaturus (ZS) is a commonly used traditional Chinese medicine with a long history of clinical application, and an excellent medicinal and edible value
The 2015 edition of the Chinese Pharmacopoeia uses synephrine as an indicator to control the quality of ZS, and stipulates that ZS is the dried fruit and young fruit of Citrus aurantium
Whether the two kinds of ZS will affect the potential toxicity of Zhi-Zi-Hou-Po decoction (ZZHPD) is unknown. This poses a huge hidden danger to the safety of the clinical use of ZZHPD, with a potential toxicity. In response to this situation, we propose a comprehensive analysis strategy based on spectrum–toxicity correlation to analyze the effects of different varieties of ZS on the potential toxicity of ZZHPD

Summary

Introduction

Aurantii Fructus Immaturus (ZS) is a commonly used traditional Chinese medicine with a long history of clinical application, and an excellent medicinal and edible value. It was first recorded in Shen-Nong-Ben-Cao-Jing (Sheng Nong’s herbal classic). Studies have demonstrated that there are some differences in chemical composition and content between the two varieties of ZS [5,6]. Compared with SZS, some flavonoids in TZS are lower in content, which are important functional ingredients in ZS. A diversified chemical composition is the material basis for the efficacy and toxicity of traditional Chinese medicine compound preparations.

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