贯叶连翘提取物对奥沙利铂诱导的神经毒性的影响:体外评价

L. Cinci, L. di Cesare Mannelli, A. Maidecchi, L. Mattoli, C. Ghelardini
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引用次数: 12

摘要

几个世纪以来,贯叶连翘(Hypericum perforatum L.)一直被用作治疗许多疾病的天然药物。神经性疼痛是基于奥沙利铂的化疗的常见副作用,经常导致治疗中断。由于其抗炎和镇痛作用,使用贯叶连翘可能是一种新的治疗神经病变的策略。本研究旨在评价贯叶连翘亲水性提取物对奥沙利铂诱导的神经毒性体外模型的影响。通过硫代巴比妥酸活性物质测定和硝基蓝四氮唑氧化试验,首先在无细胞模型中评价提取物的抗氧化潜力;在结直肠癌体外模型(HT-29细胞)中,还评估了贯叶连翘提取物降低奥沙利铂诱导的大鼠星形胶质细胞caspase-3活性的能力及其对奥沙利铂细胞毒性作用的潜在干扰。该提取物具有明显的抗氧化作用,可降低大鼠星形胶质细胞中caspase-3的活性。值得注意的是,提取物单独对HT-29细胞产生细胞毒性作用,并没有降低奥沙利铂对HT-29细胞的细胞毒性。这些数据表明,贯叶连翘可以作为一种新的治疗策略来对抗化疗引起的神经病变。
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Effects of Hypericum perforatum extract on oxaliplatin-induced neurotoxicity: in vitro evaluations
Abstract Hypericum perforatum L. has been used for centuries as a natural remedy for the treatment of many disorders. Neuropathic pain is a common side effect of oxaliplatin-based chemotherapy and often the cause of therapy discontinuation. Thanks to its anti-inflammatory and analgesic effects, the use of H. perforatum may be a novel therapeutic strategy for neuropathy. The aim of this paper was to evaluate the effect of H. perforatum hydrophilic extract on an in vitro model of oxaliplatin-induced neurotoxicity. The antioxidant potential of extract was first evaluated in cell-free models by the thiobarbituric acid-reactive substances assay and nitro blue tetrazolium oxidation test; the ability of H. perforatum extract to reduce oxaliplatin-induced caspase-3 activity in rat astrocytes and its potential interference with the cytotoxic effects of oxaliplatin in a colorectal cancer in vitro model (HT-29 cells) were also evaluated. The extract showed a significant antioxidant effect and was able to reduce caspase-3 activity in rat astrocytes. Of note, the extract alone exerted a cytotoxic effect in HT-29 cells and did not reduce the cytotoxicity of oxaliplatin in HT-29 cells. These data suggest that H. perforatum could be used as a novel therapeutic strategy for counteracting chemotherapy-induced neuropathy.
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