Effective substances and molecular mechanisms guided by network pharmacology: An example study of Scrophulariae Radix treatment of hyperthyroidism and thyroid hormone-induced liver and kidney injuries.

Autor: Sheng MY; School of Pharmacy, Hubei University of Traditional Chinese Medicine, Wuhan, 430065, China; School of Pharmacy, Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China; Hubei Institute for Drug Control, Wuhan, 430064, China; Department of Anatomy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. Electronic address: 717069153@qq.com., Peng DW; Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. Electronic address: pengdewei_1995@163.com., Peng HM; Department of Anatomy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. Electronic address: hmpeng2003@hust.edu.cn., Zhang YL; School of Pharmacy, Hubei University of Traditional Chinese Medicine, Wuhan, 430065, China. Electronic address: 2396734884@qq.com., Xiao L; Hubei Institute for Drug Control, Wuhan, 430064, China. Electronic address: 469851167@qq.com., Zhang MR; School of Pharmacy, Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. Electronic address: 2651840687@qq.com., Wang SY; School of Pharmacy, Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. Electronic address: 1226773103@qq.com., Zhao CP; School of Pharmacy, Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. Electronic address: 1484070596@qq.com., Zhu SY; School of Pharmacy, Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. Electronic address: 1351857479@qq.com., Lu JK; School of Pharmacy, Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. Electronic address: 2351862839@qq.com., Lin L; Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. Electronic address: linli@tjh.tjmu.edu.cn., Huang R; Department of Ophthalmology, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, 430061, Hubei, China; Hubei Key Laboratory of Theory and Application Research of Liver and Kidney in Traditional Chinese Medicine, China. Electronic address: 1317951740@qq.com., Nie J; School of Pharmacy, Hubei University of Traditional Chinese Medicine, Wuhan, 430065, China; Hubei Institute for Drug Control, Wuhan, 430064, China. Electronic address: niejingwh@sina.com., Fang JB; School of Pharmacy, Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. Electronic address: fangjb@hust.edu.cn.
Jazyk: angličtina
Zdroj: Journal of ethnopharmacology [J Ethnopharmacol] 2024 May 23; Vol. 326, pp. 117965. Date of Electronic Publication: 2024 Feb 28.
DOI: 10.1016/j.jep.2024.117965
Abstrakt: Ethnopharmacological Relevance: Scrophulariae Radix (Xuanshen [XS]) has been used for several years to treat hyperthyroidism. However, its effective substances and pharmacological mechanisms in the treatment of hyperthyroidism and thyroid hormone-induced liver and kidney injuries have not yet been elucidated.
Aim of the Study: This study aimed to explore the pharmacological material basis and potential mechanism of XS therapy for hyperthyroidism and thyroid hormone-induced liver and kidney injuries based on network pharmacology prediction and experimental validation.
Materials and Methods: Based on 31 in vivo XS compounds identified using ultra-performance liquid chromatography tandem quadruple exactive orbitrap high-resolution accurate-mass spectrometry (UPLC-QE-HRMS), a network pharmacology approach was used for mechanism prediction. Systematic networks were constructed to identify the potential molecular targets, biological processes (BP), and signaling pathways. A component-target-pathway network was established. Mice were administered levothyroxine sodium through gavage for 30 d and then treated with different doses of XS extract with or without propylthiouracil (PTU) for 30 d. Blood, liver, and kidney samples were analyzed using an enzyme-linked immunosorbent assay (ELISA) and western blotting.
Results: A total of 31 prototypes, 60 Phase I metabolites, and 23 Phase II metabolites were tentatively identified in the plasma of rats following the oral administration of XS extract. Ninety-six potential common targets between the 31 in vivo compounds and the diseases were identified. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that Bcl-2, BAD, JNK, p38, and ERK1/2 were the top targets. XS extract with or without PTU had the following effects: inhibition of T3/T4/fT3/fT4 caused by levothyroxine; increase of TSH levels in serum; restoration of thyroid structure; improvement of liver and kidney structure and function by elevating the activities of anti-oxidant enzymes catalase (CAT),superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px); activation anti-apoptotic proteins Bcl-2; inhibition the apoptotic protein p-BAD; downregulation inflammation-related proteins p-ERK1/2, p-JNK, and p-p38; and inhibition of the aggregation of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6, as well as immune cells in the liver.
Conclusion: XS can be used to treat hyperthyroidism and liver and kidney injuries caused by thyroid hormones through its anti-oxidant, anti-inflammatory, and anti-apoptotic properties. In addition, serum pharmacochemical analysis revealed that five active compounds, namely 4-methylcatechol, sugiol, eugenol, acetovanillone, and oleic acid, have diverse metabolic pathways in vivo and exhibit potential as effective therapeutic agents.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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