Active ingredient of aconite root against peripheral neuropathic pain is identified as neoline

The root of Aconitum carmichaeli (Ranunculaceae), is a crude drug used in traditional Chinese or Japanese kampo medicine to treat pain associated with coldness. Since aconite root is highly toxic, processing methods for detoxifying have been developed, and toxic ingredients such as aconitine and mesaconitine degrade into benzoylaconine and benzoylmesaconitine by heat-processing. Although the analgesic activity and the toxicity of mesaconitine is strong, those of benzoylmesaconitine are about 1,000-fold weaker than mesaconitine. However, in traditional medicine, processed aconite root has been used for various pain in clinic.

The present study revealed that processed aconite root could relief neuropathic pain in murine peripheral neuropathy model induced by intraperitoneal injection of oxaliplatin, paclitaxel, or the partial ligation of the sciatic nerve (Seltzer model), and identified that its active ingredient is neoline. In the plasma samples of rats treated with processed aconite root, higher concentrations of benzoylmesaconine and neoline were apparent among Aconitum alkaloids. Subcutaneous injection of benzoylmesaconine did not attenuate the hyperalgesia in mice models. Neoline is a stable compound by heat-processing of aconite root. The present results indicate that processed aconite root and its active ingredient, neoline, are promising agents for the alleviation of neuropathic pain.

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