Ginsenosides that produce differential antinociception in mice

Ginsenoside Rc, Rd, and Re induced antinociception in writhing and formalin tests among five representative ginsenosides: Rb1, Rc, Rd, Re, and Rg1. However, these ginsenosides had no effect in the tail-flick test. The antinociceptive effects induced by three ginsenosides were dose dependent. ED50 was 20.5 (7.3-57.4 mg/kg) for Rc, 17 (11.0-27.6 mg/kg) for Rd, and 3.5 (1-12 mg/ kg) for Re in the writhing test and 62 (42-90 mg/kg) for Rc, 45 (20.5-99.0 mg/kg) for Rd, and 82 (48-139 mg/kg) for Re in the second phase of the formalin test. The antinociceptive effects were not blocked by the opioid receptor antagonist naloxone in the writhing and formalin tests. These three ginsenosides did not affect motor function. Ginsenoside Rc and Rd induced hypothermia for 30 to 60 min, and ginsenoside Rc induced hyperthemia after 150 min of treatment at doses of 100 mg/kg. These results suggest that ginsenosides such as Rc, Rd, or Re inhibit mainly chemogenic pain rather than thermal pain by the nonopioid system in mice.