Iridoids isolated from Viticis Fructus inhibit paclitaxel-induced mechanical allodynia in mice
Iridoids isolated from Viticis Fructus inhibit paclitaxel-induced mechanical allodynia in mice
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DOI：
10.1007/s11418-020-01441-6
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发表时间：
2020-08
影响因子：
3.3
通讯作者：
Huanhuan Yu;Kazufumi Toume;Y. Kurokawa;T. Andoh;K. Komatsu
中科院分区：
文献类型：
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作者：
Huanhuan Yu;Kazufumi Toume;Y. Kurokawa;T. Andoh;K. Komatsu
化疗所致周围神经病(CIPN)主要表现为机械性痛觉异常和痛觉过敏，是化疗药物的主要不良反应之一。目前可用的治疗药物不足以在临床上有效地管理这种不良反应。因此，开发治疗CIPN的新型治疗药物是必要的。我们先前的研究表明，桃叶珊瑚苷和花梗内酯(1)可能是车前子抗痛觉过敏性的活性化合物。然而，由于其在车前精液中的含量较低，其活性尚未得到评价。本研究从牡荆子中分离得到1个化合物，并在分离过程中分离得到卵黄素I(2)和卵黄素II(3)。以DSS-D6为内标，经1H-核磁共振定量分析，分离得到的化合物1、2、3的纯度分别为67.15%、92.12%、86.72%。每天重复口服这三种环烯醚类化合物15 mg/kg可显著抑制PTX诱导的小鼠机械痛觉异常，提示化合物1、2和3具有抗痛觉异常的作用。本研究为纯化的化合物1的抗痛觉过敏活性提供了确证证据，同时还发现了另外两个从牡荆子中提取的活性环烯醚萜类化合物。这三种环烯醚类化合物可能是治疗CIPN的潜在候选药物。
Chemotherapy-induced peripheral neuropathy (CIPN) manifests as mechanical allodynia and hyperalgesia, and is one of the main adverse effects of chemotherapeutic agents. Currently available therapeutic drugs are not sufficiently effective for the management of this adverse effect in the clinic. Therefore, the development of novel therapeutic agents for treating CIPN is necessary. Our previous study suggested the potential of aucubin and pedicularis-lactone (1) as active compounds responsible for the anti-allodynic property of Plantaginis Semen. However, the activity of purified1has not been evaluated due to its low content in Plantaginis Semen. In the present study,1was isolated from Viticis Fructus, as well as viteoid I (2) and viteoid II (3) during the process of isolation. The purities of isolated1,2, and3were determined as 67.15%, 92.12%, and 86.72%, respectively, by quantitative1H-NMR, using DSS-d6as an internal standard. Repeated daily oral administration of these three iridoids at a dose of 15 mg/kg significantly inhibited the PTX-induced mechanical allodynia in mice, suggesting the anti-allodynic activities of1,2, and3. This study provides confirmatory evidence for the anti-allodynic activity of purified1and also reveals two additional active iridoids from Viticis Fructus. These three iridoids could be potential candidates for the treatment of CIPN.