草药AC591可预防奥沙利铂引起的动物模型和癌症患者的周围神经病变。,Frontiers in Pharmacology

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草药AC591可预防奥沙利铂引起的动物模型和癌症患者的周围神经病变。
Frontiers in Pharmacology ( IF 4.4 ) Pub Date : 2017-06-24 , DOI: 10.3389/fphar.2017.00344
Xiaolan Cheng _{1,

2} , Jiege Huo ₁ , Dawei Wang ₁ , Xueting Cai _{1,

2} , Xiaoyan Sun _{1,

2} , Wuguang Lu _{1,

2} , Yang Yang _{1,

2} , Chunping Hu _{1,

2} , Xiaoning Wang ₁ , Peng Cao _{1,

2}

Affiliation

由于严重的周围神经病变，奥沙利铂在临床上令人信服。副作用可能导致剂量减少或什至停止化疗，并且没有有效的治疗方法。AC591是黄芪桂枝五物汤的标准提取物。黄芪桂枝五物汤是“金匮要略”中记录的一种草药配方，可改善肢体麻木和疼痛。在这项研究中，我们调查了AC591是否可以预防奥沙利铂引起的周围神经病变。为了阐明这一点，建立了奥沙利铂诱导的周围神经病的大鼠模型，并且研究了AC591的神经保护作用。我们的结果表明，用AC591预处理可降低奥沙利铂诱导的冷痛觉过敏，机械性异常性疼痛以及背根神经节的形态损害。芯片分析表明，AC591的神经保护作用取决于多种分子靶标的调控以及参与炎症和免疫反应下调的途径。此外，AC591在带有CT-26癌细胞的Balb / c小鼠中增强了奥沙利铂的抗肿瘤活性。还对72例结直肠癌患者进行了AC591的疗效研究。经过四个周期的治疗，AC591治疗组（n = 36）的1-2级神经毒性百分比为25％，而对照组的发生率为55.55％（P <0.01）（n = 36）。两组之间的肿瘤反应率没有显着差异。这些证据表明AC591可以预防奥沙利铂引起的神经病变，而不会降低其抗肿瘤活性，

"点击查看英文标题和摘要"

Herbal Medicine AC591 Prevents Oxaliplatin-Induced Peripheral Neuropathy in Animal Model and Cancer Patients.

Oxaliplatin is clinically compelling because of severe peripheral neuropathy. The side effect can result in dosage reductions or even cessation of chemotherapy, and no effective treatments are available. AC591 is a standardized extract of Huangqi Guizhi Wuwu decoction, an herbal formula recorded in "Synopsis of the Golden Chamber" for improving limb numbness and pain. In this study, we investigated whether AC591 could protect against oxaliplatin-induced peripheral neuropathy. To clarify it, a rat model of oxaliplatin-induced peripheral neuropathy was established, and neuroprotective effect of AC591 was studied. Our results showed that pretreatment with AC591 reduced oxaliplatin-induced cold hyperalgesia, mechanical allodynia as well as morphological damage of dorsal root ganglion. Microarray analysis indicated the neuroprotective action of AC591 depended on the modulation of multiple molecular targets and pathways involved in the downregulation of inflammation and immune response. Moreover, AC591 enhanced the antitumor activity of oxaliplatin to some extent in Balb/c mice bearing CT-26 carcinoma cells. The efficacy of AC591 is also investigated in 72 colorectal cancer patients. After four cycles of treatment, the percentage of grades 1-2 neurotoxicity in AC591-treated group (n = 36) was 25%, whereas in the control group the incidence was 55.55% (P < 0.01) (n = 36). No significant differences in the tumor response rate between the two groups were found. These evidences suggested that AC591 can prevent oxaliplatin-induced neuropathy without reducing its antitumor activity, and may be a promising adjuvant to alleviate sensory symptoms in clinical practice.

更新日期：2019-11-01

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