Comparative Studies on the Anti-Inflammatory and Apoptotic Activities of Four Greek Essential Oils: Involvement in the Regulation of NF-κΒ and Steroid Receptor Signaling

Abstract

Essential oils (EOs) are well-known for their anti-fungal, anti-microbial, anti-inflammatory and relaxing activities. Steroid hormones, especially glucocorticoids, are also well-known for their anti-inflammatory activities and control of the hypothalamus–pituitary–adrenal (HPA) axis and glucose homeostasis. The biological activities of glucocorticoids render them the most widely prescribed anti-inflammatory drugs, despite their adverse side effects. In this study, comparative studies of the anti-inflammatory activities and interference with glucocorticoids receptor (GR) and estrogen receptor (ER) signaling of EOs from Greek Oregano, Melissa officinalis, Lavender and from the Chios Mastic, produced from the Greek endemic mastic tree, were performed in Human Embryonic Kidney 293 (HEK-293) cells. Chios Mastic (Mastiha) and oregano EOs exhibited the highest anti-inflammatory activities. The former showed a reduction in both NF-κB activity and protein levels. Mastic essential oil also caused a reduction in GR protein levels that may compensate for its boosting effect on dexamethasone (DEX)-induced GR transcriptional activation, ending up in no induction of the gluconeogenic phoshoenolpyruvate carboxykinase (PEPCK) protein levels that constitute the GR target. Oregano, Melissa officinalis and lavender EOs caused the suppression of the transcriptional activation of GR. Furthermore, the most active EO, that taken from Melissa officinalis, showed a reduction in both GR and PEPCK protein levels. Thus, the anti-inflammatory and anti-gluconeogenic activities of the EOs were uncovered, possibly via the regulation of GR signaling. Moreover, cytotoxic actions of Melissa officinalis and lavender EOs via the induction of mitochondrial-dependent apoptosis were revealed. Our results highlight these essentials oils’ anti-inflammatory and apoptotic actions in relation to their implication on the regulation of steroid hormones’ actions, uncovering their potential use in steroid therapy, with many applications in pharmaceutical and health industries as anti-cancer, anti-hyperglycemic and anti-inflammatory supplements.