Suzuki Toshiaki, Yamamoto Ayano, Ohsawa Masahiro, Motoo Yoshiharu, Mizukami Hajime, Makino Toshiaki
Department of Pharmacognosy, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, 467-8603, Japan.
Department of Cellular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya University, Nagoya, 464-8601, Japan.
J Nat Med. 2017 Oct;71(4):757-764. doi: 10.1007/s11418-017-1113-6. Epub 2017 Jul 10.
Oxaliplatin (L-OHP) is a platinum-based anticancer agent used to treat various types of cancer. It frequently causes acute and chronic peripheral neuropathies, such as cold allodynia and mechanical hyperalgesia. Ninjin'yoeito (NYT) is a formula used in traditional Japanese Kampo medicine to improve recovery from diseases and other medical disorders. We previously reported that treatment with a boiling-water extract of NYT prevented L-OHP-induced damage to neurite-like outgrowths from differentiated PC12 cells. The objectives of the present study were to evaluate the in vivo effects of NYT on L-OHP-induced neuropathic pain in mice and identify the active ingredients in NYT. Treatment with NYT extract significantly ameliorated both cold allodynia and mechanical hyperalgesia induced by L-OHP. While L-OHP treatment suppressed neurite outgrowths from primary dorsal root ganglion cells in vitro, NYT extract blocked this suppression in a concentration-dependent manner. Among the herbal components of NYT, the extract of ginseng (Panax ginseng roots) showed a protective effect against neurite damage induced by L-OHP, and one of its active ingredients was identified as ginsenoside Rg. Ginseng extract partially relieved L-OHP-induced neuropathic pain in mice. Our results suggest that NYT could be an attractive agent for treating L-OHP-induced neuropathic pain, and that the active ingredient of NYT may be ginseng.
奥沙利铂(L-OHP)是一种用于治疗多种癌症的铂类抗癌药物。它经常导致急性和慢性周围神经病变,如冷觉异常和机械性痛觉过敏。人参养荣汤(NYT)是日本传统汉方医学中用于促进疾病和其他病症康复的一种方剂。我们之前报道过,NYT的沸水提取物治疗可预防L-OHP诱导的分化PC12细胞神经突样生长受损。本研究的目的是评估NYT对小鼠L-OHP诱导的神经性疼痛的体内作用,并确定NYT中的活性成分。NYT提取物治疗显著改善了L-OHP诱导的冷觉异常和机械性痛觉过敏。虽然L-OHP治疗在体外抑制了初级背根神经节细胞的神经突生长,但NYT提取物以浓度依赖性方式阻断了这种抑制作用。在NYT的草药成分中,人参(人参根)提取物对L-OHP诱导的神经突损伤具有保护作用,其一种活性成分被鉴定为人参皂苷Rg。人参提取物部分缓解了小鼠L-OHP诱导的神经性疼痛。我们的结果表明,NYT可能是治疗L-OHP诱导的神经性疼痛的一种有吸引力的药物,并且NYT的活性成分可能是人 参。