Quercetin and phenylpropanoids are well known chemoprotective compounds identified in many plants. This study was aimed at determining their effects on activation of Nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant response element (Nrf2-ARE) signalling pathway and expression of its important downstream effector phase II detoxification enzyme glutathione-S-transferase P1 (GSTP1) in BJ foreskin fibroblasts and skin HaCaT keratinocytes. Cell lines and their corresponding Nrf2-ARE luciferase reporter cells were treated by ginger phenylpropanoids and quercetin for 10 h and the level of Nrf2 activity was subsequently determined. Both, ginger phenylpropanoids and quercetin, significantly increased the level of Nrf2 activity. Subsequent western blot analyses of proteins showed the increased expression level of glutathione-S-transferase P1 (GSTP1) in BJ cells but not in HaCaT cells. Such phenomenon of unresponsive downstream target expression in HaCaT cells was consistent with previous studies showing a constitutive expression of their GSTP1. Thus, while both ginger phenylpropanoids and quercetin have the property of increasing the level of Nrf2 both in HaCaT and in BJ cells, their effects on its downstream signalling were mediated only in BJ cells.

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This study presents the very first report on the in vitro antiviral activity of selected essential oils of Lamiaceae plant species and their monoterpenes against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Nineteen essential oils were obtained by hydrodistillation of dried plant material, and their monoterpene profiles were determined. In addition, the exact concentrations of each monoterpene that were found at a significant level were defined. Both essential oils and their monoterpene components were tested for cytotoxic and antiviral activity against SARS-CoV-2 in infected Vero 76 cells. The results showed that the essential oils of four Mentha species, i.e., M. aquatica L. cv. Veronica, M. pulegium L., M. microphylla K.Koch, and M. x villosa Huds., but also Micromeria thymifolia (Scop.) Fritsch and Ziziphora clinopodioides Lam., and five different monoterpenes, i.e., carvacrol, carvone, 1,8-cineol, menthofuran, and pulegone, inhibited the SARS-CoV-2 replication in the infected cells. However, the antiviral activity varied both among essential oils and monoterpenes. Carvone and carvacrol exhibited moderate antiviral activity with IC50 concentrations of 80.23 ± 6.07 μM and 86.55 ± 12.73 μM, respectively, while the other monoterpenes were less active (IC50 > 100.00 μM). Structure-activity relations of related monoterpenes showed that the presence of keto and hydroxyl groups is associated with the activity of carvone and carvacrol, respectively. Furthermore, the carvone-rich essential oil of M. x villosa had the greatest activity among all active essential oils (IC50 127.00 ± 4.63 ppm) while the other active oils exhibited mild (140 ppm < IC50 < 200 ppm) to weak antiviral activity (IC50 > 200 ppm). Both essential oils and monoterpenes showed limited or no cytotoxicity against Vero 76 cells. Hierarchical cluster analysis showed that the differences in the antiviral activity of essential oils were directly attributed to the antiviral efficacies of their particular single monoterpenes. The findings presented here on the novel antiviral property of plant essential oils and monoterpenes might be used in the development of different measures against SARS-CoV-2.