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黄芪:能否成为奥沙利铂诱导神经病变的辅助药物?

Astragali radix: could it be an adjuvant for oxaliplatin-induced neuropathy?

机构信息

Dept. of Neuroscience, Psychology, Drug Research and Children's Health - NEUROFARBA - Pharmacology and Toxicology Section, Florence, Italy.

Dept. of Experimental and Clinical Medicine - DECM - Section of Anatomy and Histology, University of Florence, Florence, Italy.

出版信息

Sci Rep. 2017 Feb 10;7:42021. doi: 10.1038/srep42021.

Abstract

Neurotoxicity is a major side effect of platinum derivatives both during and after treatment. In the absence of effective pharmacological compounds, the opportunity to identify safe adjuvant treatments among medicinal plants seems appropriate. Astragali radix is an adaptogenic herbal product recently analyzed in platinum-treated cancer patients. With the aim of evaluating the anti-neuropathic profile of Astragali radix, a previously characterized aqueous (Aqu) and two hydroalcoholic (20%HA and 50%HA) extracts were tested in a rat model of oxaliplatin-induced neuropathy. Repeated administrations significantly reduced oxaliplatin-dependent hypersensitivity with 50%HA, the most effective, fully preventing mechanical and thermal hypersensitivity. Ex vivo, 50%HA reduced morphometric and molecular alterations induced by oxaliplatin in peripheral nerve and dorsal-root-ganglia. In the spinal cord and in brain areas, 50%HA significantly decreased activation of microglia and astrocytes. Furthermore, 50%HA prevented the nephro- and hepato-toxicity induced by the anticancer drug. The protective effect of 50%HA did not alter oxaliplatin-induced apoptosis in colon tumors of Pirc rats, an Apc-driven model of colon carcinogenesis. The hydroalcoholic extract (50%HA) of Astragali radix relieves pain and promotes the rescue mechanisms that protect nervous tissue from the damages triggering chronic pain. A safe profile strongly suggests the usefulness of this natural product in oxaliplatin-induced neuropathy.

摘要

神经毒性是铂衍生物在治疗期间和治疗后产生的主要副作用。在缺乏有效药物化合物的情况下,从药用植物中寻找安全的辅助治疗方法似乎是合适的。黄芪是一种最近在接受铂类药物治疗的癌症患者中分析的适应原草药产品。为了评估黄芪的抗神经病变特性,我们在奥沙利铂诱导的神经病变大鼠模型中测试了先前表征的水提物(Aqu)和两种水醇提物(20%HA 和 50%HA)。重复给药可显著减轻奥沙利铂依赖性的超敏反应,其中 50%HA 的效果最显著,完全预防了机械和热超敏反应。在体外,50%HA 可减轻奥沙利铂引起的周围神经和背根神经节的形态和分子改变。在脊髓和脑区,50%HA 可显著降低小胶质细胞和星形胶质细胞的激活。此外,50%HA 可预防抗癌药物引起的肾和肝毒性。50%HA 的保护作用不会改变 Pirc 大鼠结肠肿瘤中奥沙利铂诱导的细胞凋亡,Pirc 大鼠是一种 APC 驱动的结肠癌发生模型。黄芪的水醇提物(50%HA)可缓解疼痛并促进保护神经组织免受触发慢性疼痛的损伤的挽救机制。安全的特性强烈表明这种天然产物在奥沙利铂诱导的神经病变中的有用性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ee7/5301199/b2f381ea68c1/srep42021-f1.jpg

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