Cnicin promotes functional nerve regeneration

Abstract

BackroundThe limited regenerative capacity of injured axons hinders functional recovery after nerve injury. Although no drugs are currently available in the clinic to accelerate axon regeneration, recent studies show the potential of vasohibin inhibition by parthenolide, produced in Tanacetum parthenium, to accelerate axon regeneration. However, due to its poor oral bioavailability, parthenolide is limited to parenteral administration. PurposeThis study investigates another sesquiterpene lactone, cnicin, produced in Cnicus benedictus for promoting axon regeneration. ResultsCnicin is equally potent and effective in facilitating nerve regeneration. In culture, cnicin promotes axon growth of sensory and CNS neurons from various species, including humans. Neuronal overexpression of vasohibin increases the effective concentrations comparable to parthenolide, suggesting an interaction between cnicin and vasohibin. Remarkably, intravenous administration of cnicin significantly accelerates functional recovery after severe nerve injury in various species, including the anastomosis of severed nerves. Pharmacokinetic analysis of intravenously applied cnicin shows a blood half-life of 12.7 minutes and an oral bioavailability of 84.7% in rats. Oral drug administration promotes axon regeneration and recovery after nerve injury in mice. ConclusionThese results highlight the potential of cnicin as a promising drug to treat axonal insults and improve recovery.