National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei 11031, Taiwan.
Department of Neurology, Cardinal-Tien Hospital, New Taipei City 231, Taiwan.
Int J Mol Sci. 2018 Apr 23;19(4):1258. doi: 10.3390/ijms19041258.
Liu Jun Zi Tang (LJZT) has been used to treat functional dyspepsia and depression, suggesting its effects on gastrointestinal and neurological functions. LJZT is currently used as a complementary therapy to attenuate cisplatin-induced side effects, such as dyspepsia. However, its effect on chemotherapy-induced neuropathic pain or neurotoxicity has rarely been studied. Thus, we explored potential mechanisms underlying LJZT protection against cisplatin-induced neurotoxicity. We observed that LJZT attenuated cisplatin-induced thermal hyperalgesia in mice and apoptosis in human neuroblastoma SH-SY5Y cells. Furthermore, it also attenuated cisplatin-induced cytosolic and mitochondrial free radical formation, reversed the cisplatin-induced decrease in mitochondrial membrane potential, and increased the release of mitochondrial pro-apoptotic factors. LJZT not only activated the peroxisome proliferator-activated receptor gamma coactivator 1-alpha () promoter region, but also attenuated the cisplatin-induced reduction of expression. Silencing of the gene counteracted the protection of LJZT. Taken together, LJZT mediated, through anti-oxidative effect and mitochondrial function regulation, to prevent cisplatin-induced neurotoxicity.
Liu Jun Zi Tang（LJZT）已被用于治疗功能性消化不良和抑郁症，提示其对胃肠道和神经系统功能的影响。LJZT 目前被用作减轻顺铂引起的副作用的辅助疗法，如消化不良。然而，它对化疗引起的神经性疼痛或神经毒性的影响很少被研究。因此，我们探讨了 LJZT 对顺铂诱导的神经毒性的保护作用的潜在机制。我们观察到 LJZT 减轻了顺铂诱导的小鼠热痛觉过敏和人神经母细胞瘤 SH-SY5Y 细胞的凋亡。此外，它还减轻了顺铂诱导的细胞质和线粒体自由基形成，逆转了顺铂诱导的线粒体膜电位降低，并增加了线粒体促凋亡因子的释放。LJZT 不仅激活了过氧化物酶体增殖物激活受体γ辅激活因子 1-α（PGC-1α）启动子区域，还减轻了顺铂诱导的表达减少。沉默 LJZT 的基因抵消了 LJZT 的保护作用。综上所述，LJZT 通过抗氧化作用和线粒体功能调节介导，预防顺铂诱导的神经毒性。
