Effect of ninjin'yoeito and ginseng extracts on oxaliplatin-induced neuropathies in mice

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 Rg₃. 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.