15 February 2020 : Animal Research
Network Pharmacology-Based Prediction and Verification of Qingluo Tongbi Formula to Reduce Liver Toxicity of Tripterygium wilfordii via UGT2B7 in Endoplasmic ReticulumMing Li1ABCDEF, Jing Wang2ABCDF, Ling Fu1D, Yan Lu3D, Jianya Xu14A, Lingling Zhou5A, Huaxu Zhu5A, Liang Fang1D, Zhe Feng1A, Tong Xie14A, Xueping Zhou1AG*
Med Sci Monit 2020; 26:e920376
BACKGROUND: The hepatotoxicity of Tripterygium wilfordii Hook. f. (TWHF) limits its clinic utilization. Qingluo Tongbi formula (QTF) was formulated based on a basic Chinese medicine theory. Previous studies have confirmed the safety and efficacy of QTF in treating rheumatoid arthritis. Therefore, we considered that TWHF could be detoxified based on its reasonable compatibility with QTF. We investigated the detoxicity mechanism of QTF in reducing the liver toxicity of TWHF.
MATERIAL AND METHODS: We used network pharmacology to determine the relevant metabolism targets of TWHF, focusing on the phase II metabolic enzymes uridine diphosphate-glucuronosyltransferase 1A1 (UGT1A1), UGT1A6, and UGT2B7. Based on the molecular mechanisms of these predictions and the results of the network analysis, we designed experiments to verify our hypothesis in vivo. We used western blotting, real-time quantitative polymerase chain reaction (RT-qPCR), double immunofluorescence, and laser confocal microscopy to detect the expression of UGTs. Finally, we used transmission electron microscopy to observe the endoplasmic reticulum structure.
RESULTS: The results confirmed that QTF reversed the TWHF-induced reduction of UGT content in liver microsomes, upregulated UGT1A1 and UGT1A6 but not UGT2B7 in the liver tissue. UGT2B7 expression in the liver and liver microsomes was inconsistent. QTF upregulated the expression of UGT2B7 in the endoplasmic reticulum, and QTF upregulated UGT2B7 expression levels in the endoplasmic reticulum compared with TWHF, which reduced liver toxicity. Structural changes were observed in the endoplasmic reticulum.
CONCLUSIONS: The Chinese traditional medicine compound QTF can achieve the effect of detoxification by upregulating the expression of UGT2B7 in the endoplasmic reticulum.
Keywords: drug-induced liver injury, Endoplasmic Reticulum, Glucuronosyltransferase, Medicine, Chinese Traditional, Tripterygium, Arthritis, Rheumatoid, Drug Therapy, Combination, Drugs, Chinese Herbal, Liver, Microscopy, Electron, Transmission, Microsomes, Liver, Models, Biological
12 September 2022 : EditorialEditorial: Treatment with Dual Incretin Receptor Agonists to Maintain Normal Glucose Levels May Also Maintain Normal Weight and Control Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD)
Med Sci Monit 2022; 28:e938365
16 September 2022 : Review articleEffects of Physiotherapy on Rehabilitation and Quality of Life in Patients Hospitalized for COVID-19: A Rev...
Med Sci Monit In Press; DOI: 10.12659/MSM.938141
12 September 2022 : Clinical ResearchEffect of Vitamin D Concentration on Course of COVID-19
Med Sci Monit In Press; DOI: 10.12659/MSM.937741
29 August 2022 : Database AnalysisTranscriptome Analysis of Peripheral Blood Mononuclear Cells Response in Patients with Severe COVID-19 Reve...
Med Sci Monit 2022; 28:e937532
29 Sep 2022 : Animal ResearchEffect of Antilogous Platelet-Rich Plasma on the Revascularization of Rabbit Prefabricated Flap
Med Sci Monit In Press; DOI: 10.12659/MSM.937718
26 Sep 2022 : Clinical ResearchDistribution and Determinants of Plasma Homocysteine Levels in a Preconception Population: A Retrospective ...
Med Sci Monit In Press; DOI: 10.12659/MSM.937987
26 Sep 2022 : Clinical ResearchLatency and Interpeak Interval Values of Auditory Brainstem Response in 73 Individuals with Normal Hearing
Med Sci Monit In Press; DOI: 10.12659/MSM.937847
Most Viewed Current Articles
30 Dec 2021 : Clinical ResearchRetrospective Study of Outcomes and Hospitalization Rates of Patients in Italy with a Confirmed Diagnosis o...
Med Sci Monit 2021; 27:e935379
13 Nov 2021 : Clinical ResearchAcceptance of COVID-19 Vaccination and Its Associated Factors Among Cancer Patients Attending the Oncology ...
Med Sci Monit 2021; 27:e932788
08 Mar 2022 : Review articleA Review of the Potential Roles of Antioxidant and Anti-Inflammatory Pharmacological Approaches for the Man...
Med Sci Monit 2022; 28:e936292