Myrtenol from Lavender Essential Oil Possesses Neuroprotective Effects and Promotes Neurite Outgrowth by Potentially Targeting TrkA and IGF-1R in PC12 Cells

TL;DR

Myrtenol, a compound in lavender oil, protects nerve cells and promotes growth by targeting specific receptors, offering potential for treating Alzheimer's disease.

Contribution

Identifies myrtenol as a key neuroprotective compound in lavender oil and reveals its mechanism via TrkA and IGF-1R signaling.

Findings

Myrtenol promotes neurite outgrowth and reduces cytotoxicity in PC12 cells.

It activates PLC/PKC and PI3K/AKT pathways through TrkA and IGF-1R modulation.

Myrtenol shows NGF-like activity and potential as a lead compound for neurodegeneration research.

Abstract

Alzheimer’s disease (AD) is a prevalent chronic neurodegenerative disorder; the progression of this disease is driven by cellular determinants such as oxidative stress and dysregulated neurotrophic signaling. Lavender essential oil is traditionally used in aromatherapy for neuronal regulation and neuroprotection, suggesting its potential neuroprotective effects for chronic neurodegenerative disorders like AD. However, the key active constituents responsible for its benefits and the specific molecular pharmacological mechanisms remain unclear. In this study, we isolated myrtenol from lavender essential oil under the guidance of activity evaluation. Its neuroprotective effects were evaluated in PC12 cells via neurite outgrowth, anti-Aβ/H2O2 cytotoxicity, and antioxidant assays. Targets and pathways were explored using inhibitor experiments, cell thermal shift assay (CETSA), drug affinity responsive target stability (DARTS), and Western blot. Myrtenol significantly induced neurite outgrowth in PC12 cells and effectively mitigated cytotoxicity and oxidative stress damage induced by Aβ25–35 and H2O2. Mechanistic studies revealed that myrtenol’s effects are associated with the modulation of tyrosine kinase receptor A (TrkA) and insulin-like growth factor-1 receptor (IGF-1R), activating phospholipase C (PLC)/protein kinase C (PKC) and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathways to jointly mediate neuroprotection effects against the pathology of AD. This study demonstrates that myrtenol as a highly active component of lavender essential oil possesses NGF-like neuritogenic activity and neuroprotective effects. It provides a foundation for understanding the cellular mechanisms of myrtenol as a small-molecule lead for further investigation in neurodegeneration-related research.

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