Zhu Lu-Lin, Zhang Qi, Liu Meng-Qin, Liu Sha, Liu Yu-Ling, Qin Lu-Ping, Zhang Qiao-Yan
College of Pharmaceutical Sciences, Zhejiang Chinese Medical University Hangzhou 310053, China.
School of Pharmacy, Fujian University of Traditional Chinese Medicine Fuzhou 350122, China.
Zhongguo Zhong Yao Za Zhi. 2021 Apr;46(7):1727-1737. doi: 10.19540/j.cnki.cjcmm.20201224.601.
Methotrexate(MTX) is a commonly used antimetabolite, which can be used in the treatment of a variety of diseases. However, hepatotoxicity in the use of MTX severely limits its clinical use. Therefore, how to prevent and treat hepatotoxicity of MTX has become an urgent clinical problem. This paper summarizes and analyzes relevant literatures on the prevention and treatment of hepa-totoxicity caused by MTX with traditional Chinese medicines and natural medicines in recent years. MTX-induced hepatotoxicity mechanisms include folate pathway, oxidative stress damage and adenosine pathway, of which oxidative stress theory is the main research direction. A total of 14 kinds of traditional Chinese medicine and natural medicine extracts including white peony root, and 21 kinds of natural monomer compounds, including berberine, play an anti-MTX-induced hepatotoxic effect by resisting oxidative stress, inhibiting inflammation and regulating signal pathways. According to current studies on the prevention and treatment of hepatotoxicity induced by MTX with traditional Chinese medicines and natural medicines, there are insufficiencies, such as partial and superficial mechanism studies, inadequate combination of experimental research and clinical practice, non-standard experimental design and lack of application of advanced technologies and methods. This paper systematically reviewed the effects and mechanisms of traditional Chinese medicines and natural medicines against hepatotoxicity induced by MTX and defined current studies and deficiencies, in the expectation of proposing new study strategies and directions and providing scientific basis for rational clinical use of MTX and development of new drugs against MTX hepatotoxicity.
甲氨蝶呤（MTX）是一种常用的抗代谢药物，可用于治疗多种疾病。然而，MTX使用过程中的肝毒性严重限制了其临床应用。因此，如何防治MTX肝毒性已成为临床亟待解决的问题。本文对近年来中药及天然药物防治MTX所致肝毒性的相关文献进行总结分析。MTX诱导肝毒性的机制包括叶酸途径、氧化应激损伤和腺苷途径，其中氧化应激理论是主要研究方向。包括白芍在内的14种中药及天然药物提取物，以及包括黄连素在内的21种天然单体化合物，通过抵抗氧化应激、抑制炎症和调节信号通路发挥抗MTX诱导肝毒性的作用。根据目前中药及天然药物防治MTX诱导肝毒性的研究，存在机制研究片面、肤浅，实验研究与临床实践结合不足，实验设计不规范，缺乏先进技术方法应用等不足。本文系统综述了中药及天然药物抗MTX诱导肝毒性的作用及机制，明确了目前的研究及不足，以期提出新的研究策略和方向，为MTX的合理临床应用及抗MTX肝毒性新药研发提供科学依据。
