Metapanax delavayi extract as a neurocutaneous modulator via CRHR1/POMC/MC1R signaling

Metapanax delavayi (Franch.) J. Wen & Frodin (Araliaceae) is a plant with both medicinal and edible value, but there is no study examining its effects on skin neurogenic inflammation. We investigated the anti-neurogenic inflammatory and soothing potential of Metapanax delavayi extract (MDE) in vitro using SH-SY5Y cells activated by capsaicin and HaCaT cells stimulated by substance P, and in vivo using a heat-induced zebrafish model. We found that MDE significantly inhibited TRPV1 activation and intracellular calcium influx, down-regulated neuropeptides (CGRP, NGF, substance P) and proinflammatory cytokines (IL-1α, IL-6, IL-8), and regulated emotion-related Hormones (decreased cortisol, increased β-endorphin). It also reduced heat-induced hypermotility in zebrafish. Critically, the mechanistic study suggests that biological activity may be associated with the inactivation of the CRHR1/POMC/MC1R signaling pathway. Collectively, these findings indicate that MDE possesses significant potential as a natural skincare ingredient for counteracting neurogenic inflammation associated with sensitive skin.