Huang Xuedan, Hyuga Sumiko, Ito Michiho, Goda Yukihiro, Kobayashi Yoshinori
Oriental Medicine Research Center, School of Pharmacy, Kitasato University, Tokyo, Japan.
National Institute of Health Sciences, Kawasaki, Japan.
J Nat Med. 2025 Jan;79(1):107-121. doi: 10.1007/s11418-024-01853-8. Epub 2024 Oct 29.
Currently, there are no effective prophylactic or therapeutic drugs for the treatment of paclitaxel (PTX)-induced peripheral neuropathic pain (PTX-PNP), highlighting the urgent need for the development of effective prophylactic and therapeutic drugs. In this study, we initially compared the efficacy of Ephedra Herb extract (EHE) with that of ephedrine alkaloids-free Ephedra Herb extract (EFE), which lacked ephedrine alkaloids (EAs)-associated side effects, against the onset of PTX-induced mechanical allodynia, thermal hyperalgesia, and cold allodynia in mice. EHE and EFE demonstrated comparable preventive effects on the PTX-PNP in a dose-dependent manner. These results indicated that the preventive properties of EHE were independent of the EAs. Since elderly people are overwhelmingly more susceptible to developing cancer, we considered that EFE has greater benefits than EHE, so we conducted a study focused on the effects of EFE. EFE showed dose-dependent preventive effects on the onset of PTX-PNP. As a result of detailed investigation, coadministration of PTX and EFE (Co-EFE) was more effective than preadministration of EFE alone (Pre-EFE). And the effects of Co-EFE was same with the effect of preadministration of EFE and then coadministration of PTX and EFE (P&C-EFE). Additionally, Co-EFE after the onset of PTX-PNP improved PTX-induced mechanical allodynia, thermal hyperalgesia, and cold allodynia, confirming the therapeutic efficacy of EFE on PTX-PNP. In contrast, goshajinkigan, a Kampo medicine, and diclofenac, a non-steroidal anti-inflammatory drug, showed minimal therapeutic effects on PTX-PNP. These findings demonstrate the significant potential of EFE as a novel, safe prophylactic and therapeutic agent against PTX-PNP.
目前，尚无有效的预防或治疗药物用于治疗紫杉醇（PTX）诱导的周围神经病理性疼痛（PTX-PNP），这凸显了开发有效预防和治疗药物的迫切需求。在本研究中，我们首先比较了麻黄提取物（EHE）与无麻黄碱生物碱的麻黄提取物（EFE）对小鼠PTX诱导的机械性异常性疼痛、热痛觉过敏和冷异常性疼痛发作的疗效，后者缺乏与麻黄碱生物碱（EAs）相关的副作用。EHE和EFE对PTX-PNP均表现出剂量依赖性的可比预防作用。这些结果表明，EHE的预防特性与EAs无关。由于老年人患癌症的易感性极高，我们认为EFE比EHE有更大的益处，因此我们开展了一项聚焦于EFE作用的研究。EFE对PTX-PNP的发作表现出剂量依赖性的预防作用。详细研究结果表明，PTX与EFE联合给药（Co-EFE）比单独预先给予EFE（Pre-EFE）更有效。并且Co-EFE的效果与预先给予EFE然后PTX与EFE联合给药（P&C-EFE）的效果相同。此外，PTX-PNP发作后给予Co-EFE可改善PTX诱导的机械性异常性疼痛、热痛觉过敏和冷异常性疼痛，证实了EFE对PTX-PNP的治疗效果。相比之下，汉方药物柴胡桂枝干姜汤和非甾体抗炎药双氯芬酸对PTX-PNP的治疗效果甚微。这些发现表明EFE作为一种新型、安全的预防和治疗PTX-PNP的药物具有巨大潜力。
