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Altered Iron-Mediated Metabolic Homeostasis Governs the Efficacy and Toxicity of tripterygium glycosides tablets Against Rheumatoid Arthritis

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Engineering 2024年第8期39卷 166-179页

作者： Zihe Ding Xiaoyue Wang Yi Zhang Jian Liu Lei Wan Tao Li Lin Chen Na Lin Yanqiong Zhang State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs Institute of Chinese Materia MedicaChina Academy of Chinese Medical SciencesBeijing 100700China The First Affiliated Hospital of Anhui University of Chinese Medicine Hefei 230038China

Rheumatoid arthritis(RA),a globally increasing autoimmune disorder,is associated with increased disability rates due to the disruption of iron *** glycoside tablets(TGTs),a tripterygium wilfordii Hook.f.(TwHF)-based therapy,exhibit satisfactory clinical efficacy for RA ***,drug-induced liver injury(DILI)remains a critical issue that hinders the clinical application of TGTs,and the molecular mechanisms underlying the efficacy and toxicity of TGTs in RA have not been fully *** address this problem,we integrated clinical multi-omics data associated with the anti-RA efficacy and DILI of TGTs with the chemical and target profiling of TGTs to perform a systematic network ***,we identified effective and toxic targets following experimental validation in a collagen-induced arthritis(CIA)mouse *** different transcriptome–protein–metabolite profiles distinguishing patients with favorable TGTs responses from those with poor outcomes were ***,the clinical efficacy and DILI of TGTs against RA were associated with metabolic homeostasis between iron and bone and between iron and lipids,***,the signal transducer and activator of transcription 3(STAT3)–hepcidin(HAMP)/lipocalin 2(LCN2)–tartrate-resis tant acid phosphatase type 5(ACP5)and STAT3–HAMP–acyl-CoA synthetase long-chain family member 4(ACSL4)–lysophosphatidylcholine acyltransferase 3(LPCAT3)axes were identified as key drivers of the efficacy and toxicity of *** play dual roles in ameliorating CIA-induced pathology and in inducing hepatic dysfunction,disruption of lipid metabolism,and hepatic lipid ***,TGTs effectively reversed“iron–bone”disruptions in the inflamed joint tissues of CIA mice by inhibiting the STAT3–HAMP/LCN2–ACP5 axis,subsequently leading to“iron–lipid”disturbances in the liver tissues via modulation of the STAT3–HAMP–ACSL4–LPCAT3 *** bidirectional validatio

关键词： tripterygium glycosides tablets Rheumatoid arthritis Iron metabolism Clinical efficacy Drug-induced liver injury Clinical multi-omics data analysis

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