Integrated chemical characterization, metabolite profiling, and pharmacokinetics analysis of Zhijun Tangshen Decoction by UPLC-Q/TOF-MS

Qingheng Tong; Yueyue Chang; Guanxiong Shang; Jiu Yin; Xiaoqi Zhou; Suwei Wang; Xiaofeng Yan; Fangfang Zhang; Suqin Wang; Weifeng Yao

doi:10.3389/fphar.2024.1363678

Integrated chemical characterization, metabolite profiling, and pharmacokinetics analysis of Zhijun Tangshen Decoction by UPLC-Q/TOF-MS

Front Pharmacol. 2024 Mar 8:15:1363678. doi: 10.3389/fphar.2024.1363678. eCollection 2024.

Authors

Affiliations

¹ Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China.
² Huai'an TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Huai'an, China.

^# Contributed equally.

Abstract

Diabetic nephropathy (DN) is the main cause of end-stage renal disease worldwide and a major public issue affecting the health of people. Therefore, it is essential to explore effective drugs for the treatment of DN. In this study, the traditional Chinese medicine (TCM) formula, Zhijun Tangshen Decoction (ZJTSD), a prescription modified from the classical formula Didang Decoction, has been used in the clinical treatment of DN. However, the chemical basis underlying the therapeutic effects of ZJTSD in treating DN remains unknown. In this study, compounds of ZJTSD and serum after oral administration in rats were identified and analyzed using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS). Meanwhile, a semi-quantitative approach was used to analyze the dynamic changes in the compounds of ZJTSD in vivo. UPLC-Q/TOF-MS analysis identified 190 compounds from ZJTSD, including flavonoids, anthraquinones, terpenoids, phenylpropanoids, alkaloids, and other categories. A total of 156 xenobiotics and metabolites, i.e., 51 prototype compounds and 105 metabolites, were identified from the compounds absorbed into the blood of rats treated with ZJTSD. The results further showed that 23 substances with high relative content, long retention time, and favorable pharmacokinetic characteristics in vivo deserved further investigations and validations of bioactivities. In conclusion, this study revealed the chemical basis underlying the complexity of ZJTSD and investigated the metabolite profiling and pharmacokinetics of ZJTSD-related xenobiotics in rats, thus providing a foundation for further investigation into the pharmacodynamic substance basis and metabolic regulations of ZJTSD.

Keywords: Zhijun Tangshen Decoction; compounds absorbed into blood; pharmacokinetics; traditional Chinese medicine; ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was supported by the Plan for Innovation Capacity Building in Huai’an City-Key Lab (Huai’an Key Laboratory of TCM Prevention and Treatment of Chronic Kidney Diseases) (Project No. HAP202205) and Natural Science Foundation of Nanjing University of Chinese Medicine (Project No. XZR2020085).