Evaluation of Rhodojaponin III from Rhododendron molle G. Don on oral antinociceptive activity, mechanism of action, and subacute toxicity in rodents.

ETHNOPHARMACOLOGICAL RELEVANCE

In Chinese traditional medicine, Rhododendron molle G. Don is a recognized herb to ease pain. Rhodojaponin III (RJ-III) has been identified as the main pharmacological activity and toxic component of the herb; however, oral antinociception and mechanism of RJ-III have not yet been investigated.

AIM OF THE STUDY

The significance of this study is to evaluate the effects of RJ-III on nociceptive and neuropathic pain, and to preliminarily explore the underlying mechanisms and subacute toxicity.

MATERIALS AND METHODS

The antinociception of RJ-III was evaluated by hot plate, tail-immersion, acetic acid writhing, formalin test and chronic constriction injury (CCI) model in rodents. An experimental validation was conducted using whole-cell patch clamp technique based on the most likely mechanisms of action after screening and prediction by molecular docking study. In addition, the oral subacute toxicity of RJ-III was assessed.

RESULTS

Behavioral experiments showed that RJ-III (0.20 mg/kg) reduced the latency of the nociceptive response in the hot plate and tail-immersion tests. Acetic acid and formalin-induced pain were significantly inhibited by RJ-III (0.10 and 0.05 mg/kg, respectively). Furthermore, 0.30 mg/kg of RJ-III improved hyperalgesia in the CCI-induced rats. Based on molecular docking results, electrophysiological experiments were used to demonstrate mild inhibition of voltage-gated sodium channel-related subtypes. Additionally, oral subacute toxicity that may cause leukopenia and abnormal liver function requires further attention in subsequent studies.

CONCLUSION

RJ-III mildly blocks voltage-gated sodium channel to inhibit nociceptive pain and peripheral neuralgia, but 0.375 mg/kg and above may cause side effect after long-term oral administration.