ArticleFrontiers in cell and developmental biology2025
Exploring the protective mechanisms of the yunpi jiedu tongluo qushi decoction on methotrexate-induced reproductive damage in male rats based on Nrf2/HO-1 signaling pathway.
Article in Frontiers in cell and developmental biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Methotrexate (MTX), a folate antagonist, is widely used in the treatment of tumors and autoimmune diseases such as rheumatoid arthritis (RA), due to its antiproliferative, antimetabolic, and potent anti-inflammatory properties. However, high-dose or long-term use of MTX can result in toxicity to the gastrointestinal, hemopoietic, and reproductive tissues. Yunpi Jiedu Tongluo Qushi Decoction (YJT), an effective Chinese herbal formula, is utilized in RA treatment to mitigate the toxic and side effect of MTX. Despite its clinical application, the precise effects and the underlying mechanisms through which it mitigates reproductive damage have yet to be elucidated. Purpose: This study was conducted to investigate the protective effects and mechanisms of YJT against MTX-induced reproductive toxicity. Methods: Here we used an integrated approach combining Ultra Performance Liquid Chromatography-Mass Spectrometry (UPLC-MS), Results: We identified nine active ingredients in YJT that contributed to its efficacy. YJT alleviated testicular damage in MTX-exposed rats, resolved abnormalities of sperm morphology, structure, and quality, decreased the number of TUNEL-positive cells in testicular tissue, and reduced oxidative stress (OS). YJT affected GC2spd cell apoptosis by regulating OS response. Both Conclusion: Collectively, our findings indicate that YJT protects against MTX-induced apoptosis in spermatogenic cells by inhibiting OS and Nrf2/HO-1 signaling pathway. This study provides a theoretical foundation and experimental basis for the use of YJT to alleviate MTX-induced reproductive toxicity.
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