Ferrara Valentina, Zonfrillo Beatrice, Bellumori Maria, Innocenti Marzia, Micheli Laura, Maggini Valentina, Venturi Daniel, Gallo Eugenia, Bogani Patrizia, Di Cesare Mannelli Lorenzo, Ghelardini Carla, Mulinacci Nadia, Firenzuoli Fabio
Department of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), Section of Pharmacology and Toxicology, University of Florence, 50139 Florence, Italy.
Department of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), Section of Pharmaceutical and Nutraceutical Sciences, University of Florence, via Ugo Schiff 6, 50019 Sesto Fiorentino, Italy.
Nutrients. 2025 Aug 8;17(16):2588. doi: 10.3390/nu17162588.
: Chemotherapy-induced neuropathic pain is a major side effect of antineoplastic treatment. This study investigated the neuroprotective potential of L. extracts containing the N-alkylamide spilanthol, phenolic acids, and glycosylated flavonoids. : Hydroalcoholic extracts of aerial parts (AP) and roots (R) of in vitro seedlings were quali-quantitatively characterized by HPLC-DAD-MS and by H-NMR. Different concentrations (15-150 µg/mL) of AP and R were tested in SH-SY5Y cells differentiated into neurons exposed to oxaliplatin (10 µM), assessing cell viability (MTT), cytotoxicity (LDH), SOD activity, and expression of ATF-3, Ire1α, and Nf-H genes. To evaluate the impact on neuropathic pain, CD-1 mice were treated intraperitoneally with oxaliplatin (2.4 mg/kg), the effect of AP and R extracts (200-1200 mg/kg) were measured by the cold plate test. : AP extract was rich in phenols and alkylamides, whereas R extract showed higher phenolic levels but lower alkylamides content. Both extracts significantly reduced mortality and cytotoxicity and counteracted oxidative imbalance by enhancing SOD activity. Gene expression analysis confirmed their neuroprotective effects. In vivo, oxaliplatin induced a 50% reduction in pain threshold, while acute treatment with AP and R extracts dose-dependently alleviated neuropathic pain. Despite the lower spilanthol content in R extract, its efficacy was comparable to AP, suggesting an important role of phenolic compounds. : Extracts from both aerial parts and roots of show promise in alleviating chemotherapy-induced neuropathy through mechanisms not solely related to spilanthol. Further studies to elucidate the contribution of phenolic components are desirable.
化疗引起的神经性疼痛是抗肿瘤治疗的主要副作用。本研究调查了含有N-烷基酰胺类辣椒素、酚酸和糖基化黄酮类化合物的L.提取物的神经保护潜力。：通过HPLC-DAD-MS和H-NMR对体外幼苗地上部分（AP）和根（R）的水醇提取物进行了定性和定量表征。在分化为神经元的SH-SY5Y细胞中测试了不同浓度（15-150μg/mL）的AP和R，这些细胞暴露于奥沙利铂（10μM）中，评估细胞活力（MTT）、细胞毒性（LDH）、SOD活性以及ATF-3、Ire1α和Nf-H基因的表达。为了评估对神经性疼痛的影响，给CD-1小鼠腹腔注射奥沙利铂（2.4mg/kg），通过冷板试验测量AP和R提取物（200-1200mg/kg）的效果。：AP提取物富含酚类和烷基酰胺类化合物，而R提取物显示出较高的酚类水平但较低的烷基酰胺类化合物含量。两种提取物均显著降低死亡率和细胞毒性，并通过增强SOD活性抵消氧化失衡。基因表达分析证实了它们的神经保护作用。在体内，奥沙利铂使疼痛阈值降低了50%，而AP和R提取物的急性治疗剂量依赖性地减轻了神经性疼痛。尽管R提取物中辣椒素含量较低，但其疗效与AP相当，表明酚类化合物具有重要作用。：L.地上部分和根的提取物在减轻化疗引起的神经病变方面显示出前景，其作用机制不仅与辣椒素有关。进一步研究以阐明酚类成分的作用是可取的。
