Fast-Acting and Receptor-Mediated Regulation of Neuronal Signaling Pathways by Copaiba Essential Oil.

Yasuyo Urasaki,Cody Beaumont,Thuc T Le,Jeffery N Talbot,David K Hill,Michelle Workman

doi:10.3390/ijms21072259

Yasuyo Urasaki, Cody Beaumont + Show 4 more

Open Access

https://doi.org/10.3390/ijms21072259

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Abstract

This study examined the biological activities of copaiba essential oil via measurement of its effects on signaling pathways in the SH-SY5Y neuronal cell line. Nanofluidic proteomic technologies were deployed to measure the phosphorylation of biomarker proteins within the signaling cascades. Interestingly, copaiba essential oil upregulated the pI3K/Akt/mTOR, MAPK, and JAK/STAT signaling pathways in neuronal cells. The effects of copaiba essential oil peaked at 30 min post-treatment, with a half-maximal effective concentration (EC50) of approximately 80 ng/mL. Treatment with cannabinoid receptor 2 (CB2) agonist AM1241 or the inverse agonist BML190 abrogated the regulatory effects of copaiba essential oil on the pI3K/Akt/mTOR signaling pathway. Surprisingly, copaiba essential oil also activated the apoptosis signaling pathway and reduced the viability of SH-SY5Y cells with an EC50 of approximately 400 ng/mL. Furthermore, β-caryophyllene, a principal constituent of copaiba essential oil, downregulated the pI3K/Akt/mTOR signaling pathway. Taken together, the findings indicated that copaiba essential oil upregulated signaling pathways associated with cell metabolism, growth, immunity, and apoptosis. The biological activities of copaiba essential oil were determined to be fast acting, CB2 mediated, and dependent on multiple chemical constituents of the oil. Nanofluidic proteomics provided a powerful means to assess the biological activities of copaiba essential oil.

Highlights

Copaiba essential oil is a concentrated liquid obtained by steam distillation of the oleoresin of the copaiba tree
Ten copaiba essential oil samples with different batch numbers were analyzed with gas chromatography coupled with mass spectrometry (GC–MS) for their terpene compositions
Out of approximately 60 terpenes identified in copaiba essential oil, eleven major terpenes are summarized in Figure 1A and Table 1, including α-cubebene, α-copaene, β-elemene, β-caryophyllene, γ-elemene, α-bergamotene, α-humulene, trans-cadina-1(6),4-diene, germacrene D, β-bisabolene, and ∆-cadinene

Summary

Introduction

Copaiba essential oil is a concentrated liquid obtained by steam distillation of the oleoresin of the copaiba tree. Copaiba essential oil is highly versatile and broadly utilized across multiple industries, including the cosmetic, food and wellness industries [1,2]. Copaiba essential oil is being used extensively for its fragrant and emollient properties in various cosmetic products. The U.S Food and Drug Administration has approved the use of copaiba essential oil as a flavoring agent in foods and beverages [3]. Copaiba essential oil contains complex mixtures of terpenes that exert a broad range of biological activities, including antimicrobial, antifungal, antiparasite, anti-inflammatory, and anticancer activities [2]. Β-caryophyllene, a major terpene of copaiba essential oil, selectively binds to cannabinoid receptor 2 (CB2) [4]. Activation of CB2 is a therapeutic strategy for the treatment of multiple medical conditions, including pain and inflammation [5,6,7]

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