Keishikaryukotsuboreito Potentiates NGF-Induced Neurite Outgrowth in PC12 Cells

TL;DR

Keishikaryukotsuboreito (KKT) boosts nerve growth factor effects in cells, aiding neuron growth through a specific signaling pathway.

Contribution

KKT enhances NGF-induced neurite outgrowth via NGF–TrkA signaling without altering NGF potency.

Findings

KKT enhances NGF-induced neurite outgrowth in PC12 cells in a concentration-dependent manner.

The effect of KKT is entirely dependent on NGF–TrkA signaling pathway activation.

KT does not show the same enhancement as KKT despite containing similar herbs.

Abstract

Keishikaryukotsuboreito (KKT) is a Kampo formula prescribed for neuropsychiatric symptoms, whereas Keishito (KT), despite including most of the constituent herbs, is not indicated for such conditions, suggesting distinct biological actions. We examined whether KT and KKT modulate nerve growth factor (NGF)-induced neurite outgrowth in PC12 cells. Cells were stimulated with NGF in the presence or absence of KT or KKT, and neurite extension was quantified. The involvement of NGF receptor signaling was assessed using the Trk inhibitor K-252a. KKT, but not KT, enhanced NGF-induced neurite outgrowth in a concentration-dependent manner without affecting basal morphology. Pharmacological analysis showed that KKT increased the maximal NGF-induced neurite response (Emax) without altering NGF potency (EC50). K-252a completely abolished NGF-induced neurite extension and KKT-mediated enhancement, indicating that the effect was entirely dependent on NGF–TrkA signaling. These findings demonstrate that KKT selectively augments NGF-elicited neuronal differentiation and suggest translational relevance as a neurotrophic strategy.

Figures