Antinociceptive and anti-inflammatory effects of ginsenoside Rf in a rat model of incisional pain

Abstract

BackgroundGinseng saponin has long been used as a traditional Asian medicine and is known to be effective in treating various kinds of pain. Ginsenoside Rf is one of the biologically active saponins found in ginseng. We evaluated ginsenoside Rf’s antinociceptive and anti-inflammatory effects, and its mechanism of action on adrenergic and serotonergic receptors, in an incisional pain model.MethodsMechanical hyperalgesia was induced via plantar incision in rats followed by intraperitoneal administration of increasing doses of ginsenoside Rf (vehicle, 0.5 mg/kg, 1 mg/kg, 1.5 mg/kg, and 2 mg/kg). The antinociceptive effect was also compared in a Positive Control Group that received a ketorolac (30 mg/kg) injection, and the Naïve Group, which did not undergo incision. To evaluate the mechanism of action, rats were treated with prazosin (1 mg/kg), yohimbine (2 mg/kg), or ketanserin (1 mg/kg) prior to receiving ginsenoside Rf (1.5 mg/kg). The mechanical withdrawal threshold was measured using von Frey filaments at various time points before and after ginsenoside Rf administration. To evaluate the anti-inflammatory effect, serum interleukin (IL)-1β, IL-6, and tumor necrotizing factor-α levels were measured.ResultsGinsenoside Rf increased the mechanical withdrawal threshold significantly, with a curvilinear dose–response curve peaking at 1.5 mg/kg. IL-1β, IL-6, and tumor necrotizing factor-α levels significantly decreased after ginsenoside Rf treatment. Ginsenoside Rf’s antinociceptive effect was reduced by yohimbine, but potentiated by prazosin and ketanserin.ConclusionIntraperitoneal ginsenoside Rf has an antinociceptive effect peaking at a dose of 1.5 mg/kg. Anti-inflammatory effects were also detected.

Ginsenoside Rf relieves mechanical hypersensitivity, depression‐like behavior, and inflammatory reactions in chronic constriction injury rats

“…Pronociceptive IL‐1β and IL‐18 are two members of IL‐1 family, and their activity can be blocked by to their specific antagonists IL‐1RA and IL‐18 BP (anti‐inflammatory factors), respectively (Pilat et al, ; Samarani et al, ). We showed that CCI induced upregulation of IL‐1β, IL‐18, and IL‐6 in both the spinal cord and the DRG, which is consistent with previous studies (M. K. Kim et al, ; Sommer et al, ; Wolf et al, ). Previous findings indicate that IL‐10 and other anti‐inflammatory factors are not naturally produced under neuropathic pain conditions (Gonzalez et al, ; Ledeboer et al, ).…”

“…In this study, we found that ginsenoside Rf significantly reduced IL‐1β and IL‐6 in both the spinal cord and the DRG. These findings were in line with a previous study showing that ginsenoside Rf restored the elevated IL‐1β and IL‐6 in an acute pain rat model with plantar incision (M. K. Kim et al, ). We also observed decreased protein level of IL‐18 in the DRG but not in the spinal cord of CCI rats after chronic treatment of ginsenoside Rf (Figure b,d).…”

“…Additionally, repeated chronic treatment of Rf (Days 7 to 14) alleviated pain development in CCI. Consistent with previous reports (M. K. Kim et al, ; Nemmani & Ramarao, ), ginsenoside Rf at tested doses is well tolerated. The fact that gross locomotion of CCI rats was not changed by ginsenoside Rf excluded the possibility that the reduced responses to von Frey filament stimulation is due to motor disability.…”

“…Several studies have shown modest antinociceptive action of ginsenoside Rf in acute pain behaviors in animals subjected to the acetic acid abdominal constriction, formalin injection (Mogil, Shin, McCleskey, Kim, & Nah, ), and plantar incision (M. K. Kim et al, ). Ginsenoside Rf can also enhance kappa opioid receptor‐mediated analgesia in rodents (Nemmani & Ramarao, ).…”

“…Ginsenoside Rf was tested for its preventive, acute, and chronic effects on mechanical pain hypersensitivity under three different timelines. Ginsenoside Rf administration (doses and route of administration) were based on our preliminary experiments and previous studies (Ahn, Siddiqi, Aceituno, Simu, & Yang, ; D. H. Kim et al, ; M. K. Kim et al, ; Nemmani & Ramarao, ). When its preventive effect was tested, ginsenoside Rf was administered intraperitoneally twice daily for 7 days immediately before CCI, and PWT was tested every other day for 14 days after CCI.…”