Integrated Chemical Characterization, Metabolite Profiling, and Pharmacokinetics Analysis of Zhijun Tangshen Decoction by UPLC-Q/TOF-MS

Overview

Journal Front Pharmacol

Date 2024 Mar 25

PMID 38523634

Authors

Qingheng Tong

Yueyue Chang

Guanxiong Shang

Jiu Yin

Xiaoqi Zhou

Suwei Wang

Xiaofeng Yan

Fangfang Zhang

Suqin Wang

Weifeng Yao

Affiliations

Soon will be listed here.

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 . 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 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.

References

Guo J, Chen H, Zhao X, Zhao L, Tong X . Diabetic kidney disease treated with a modified Shenzhuo formula derived from Traditional Chinese Medicine: a case report. J Tradit Chin Med. 2020; 37(6):854-861. View

Gong G, Tang W, Zhou Z, Jiang Y, Wang C, Cheng H . Potential efficacious materials investigation of Yi-Yi Mixture based on Metabolome-oriented network pharmacology strategy. J Chromatogr B Analyt Technol Biomed Life Sci. 2022; 1197:123199. DOI: 10.1016/j.jchromb.2022.123199. View

Huang Q, Zhang F, Liu S, Jiang Y, Ouyang D . Systematic investigation of the pharmacological mechanism for renal protection by the leaves of Eucommia ulmoides Oliver using UPLC-Q-TOF/MS combined with network pharmacology analysis. Biomed Pharmacother. 2021; 140:111735. DOI: 10.1016/j.biopha.2021.111735. View

Dey P, Kundu A, Lee H, Kar B, Vishal V, Dash S . Ameliorates Streptozotocin-Induced Diabetic Nephropathy through Antioxidant and Anti-Inflammatory Pathways. Molecules. 2022; 27(15). PMC: 9370403. DOI: 10.3390/molecules27154985. View

Del Vecchio L, Beretta A, Jovane C, Peiti S, Genovesi S . A Role for SGLT-2 Inhibitors in Treating Non-diabetic Chronic Kidney Disease. Drugs. 2021; 81(13):1491-1511. DOI: 10.1007/s40265-021-01573-3. View

Garofalo C, Borrelli S, Liberti M, Andreucci M, Conte G, Minutolo R . SGLT2 Inhibitors: Nephroprotective Efficacy and Side Effects. Medicina (Kaunas). 2019; 55(6). PMC: 6630922. DOI: 10.3390/medicina55060268. View

Liang J, Xu F, Zhang Y, Huang S, Zang X, Zhao X . The profiling and identification of the absorbed constituents and metabolites of Paeoniae Radix Rubra decoction in rat plasma and urine by the HPLC-DAD-ESI-IT-TOF-MS(n) technique: a novel strategy for the systematic screening and identification of.... J Pharm Biomed Anal. 2013; 83:108-21. DOI: 10.1016/j.jpba.2013.04.029. View

Li Z, Deng H, Guo X, Yan S, Lu C, Zhao Z . Effective dose/duration of natural flavonoid quercetin for treatment of diabetic nephropathy: A systematic review and meta-analysis of rodent data. Phytomedicine. 2022; 105:154348. DOI: 10.1016/j.phymed.2022.154348. View

Wei W, An Y, Li Z, Wang Y, Ji H, Hou J . Simultaneous determination of resibufogenin and its eight metabolites in rat plasma by LC-MS/MS for metabolic profiles and pharmacokinetic study. Phytomedicine. 2019; 60:152971. DOI: 10.1016/j.phymed.2019.152971. View

10.

Cui H, Zhang L, Luo Y, Yuan K, Huang Z, Guo Y . A Purified Anthraquinone-Glycoside Preparation From Rhubarb Ameliorates Type 2 Diabetes Mellitus by Modulating the Gut Microbiota and Reducing Inflammation. Front Microbiol. 2019; 10:1423. PMC: 6603233. DOI: 10.3389/fmicb.2019.01423. View

11.

Tang Y, Xu D, Yue S, Chen Y, Fu R, Bai X . Modern research thoughts and methods on bio-active components of TCM formulae. Chin J Nat Med. 2022; 20(7):481-493. DOI: 10.1016/S1875-5364(22)60206-1. View

12.

Chen L, Cao H, Huang Q, Xiao J, Teng H . Absorption, metabolism and bioavailability of flavonoids: a review. Crit Rev Food Sci Nutr. 2021; 62(28):7730-7742. DOI: 10.1080/10408398.2021.1917508. View

13.

Ning Z, Zhai L, Huang T, Peng J, Hu D, Xiao H . Identification of α-glucosidase inhibitors from cyclocarya paliurus tea leaves using UF-UPLC-Q/TOF-MS/MS and molecular docking. Food Funct. 2019; 10(4):1893-1902. DOI: 10.1039/c8fo01845f. View

14.

Zhao G, Zhao W, Han L, Ding J, Chang Y . Metabolomics analysis of sea cucumber (Apostichopus japonicus) in different geographical origins using UPLC-Q-TOF/MS. Food Chem. 2020; 333:127453. DOI: 10.1016/j.foodchem.2020.127453. View

15.

Zhou M, Huo J, Wang C, Wang W . UPLC/Q-TOF MS Screening and Identification of Antibacterial Compounds in (Thunb.) Vahl Leaves. Front Pharmacol. 2022; 12:704260. PMC: 8831367. DOI: 10.3389/fphar.2021.704260. View

16.

Zhao J, Yang J, Xie Y . Improvement strategies for the oral bioavailability of poorly water-soluble flavonoids: An overview. Int J Pharm. 2019; 570:118642. DOI: 10.1016/j.ijpharm.2019.118642. View

17.

Li C, Jia W, Yang J, Cheng C, Olaleye O . Multi-compound and drug-combination pharmacokinetic research on Chinese herbal medicines. Acta Pharmacol Sin. 2022; 43(12):3080-3095. PMC: 9483253. DOI: 10.1038/s41401-022-00983-7. View

18.

Sang Q, Jia Q, Zhang H, Lin C, Zhao X, Zhang M . Chemical profiling and quality evaluation of Zhishi-Xiebai-Guizhi Decoction by UPLC-Q-TOF-MS and UPLC fingerprint. J Pharm Biomed Anal. 2020; 194:113771. DOI: 10.1016/j.jpba.2020.113771. View

19.

Hu Q, Qu C, Xiao X, Zhang W, Jiang Y, Wu Z . Flavonoids on diabetic nephropathy: advances and therapeutic opportunities. Chin Med. 2021; 16(1):74. PMC: 8349014. DOI: 10.1186/s13020-021-00485-4. View

20.

Yin J, Zhang X, Zhang Y, Ma Y, Li L, Li D . Comprehensive Study of the in Vivo and in Vitro Metabolism of Dietary Isoflavone Biochanin A Based on UHPLC-Q-TOF-MS/MS. J Agric Food Chem. 2019; 67(45):12481-12495. DOI: 10.1021/acs.jafc.9b05776. View