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  • Moreover the imbalance between pro and anti inflammatory


    Moreover, the imbalance between pro and anti-inflammatory cytokine production is present in various types of diseases. The use of substances able to induce anti-inflammatory cytokines could represent an important advance in the therapeutic treatment of a range of diseases. In this context, medicinal plants and their secondary metabolites found worldwide stand out as an interesting option for the discovery of new bioactive molecules, especially as an alternative to reduce the inflammatory process (de Cássia da Silveira e Sá et al., 2013). Natural products may, for example, be strong modulators of TNF-α production, a strategic cytokine for the control of neuropathic pain (Leung and Cahill, 2010; Paul et al., 2006). In this field of research, the essential oils (EOs) and their main compounds (monoterpenes) are noteworthy for exhibiting a wide range of bioactive new entities with appreciable anti-inflammatory profiles.
    Monoterpenes Monoterpenes consist of two isoprene units, which are formed by 5-carbons (C5) joined in a head-to-tail fashion (Fig. 1). The biochemically active isoprene units were identified as the diphosphate (pyrophosphate) esters dimethylallyl diphosphate (DMAPP) and isopentenyl diphosphate (IPP) (Dewick, n.d.). Terpenes are a large class of organic chemical compounds of natural origin. This class of secondary metabolites comprises about 90% of EO components and a variety of other compounds (Bakkali et al., 2008). Monoterpenes are the main active ingredients of essential oils with a number of biological activities, such as anti-cancer, antimicrobial, antioxidant, antiviral, analgesic and anti-inflammatory effects (Brito et al., 2012; Guimarães et al., 2013; Kozioł et al., 2014; Quintans et al., 2013; Santos et al., 2015; Siqueira-Lima et al., 2014; Aumeeruddy-Elalfi et al., 2018). Some studies report that monoterpenes are promising in relation to the modulation of cytokines because their lipophilic characteristics favor their A-317491 and rapid action (Spelman et al., 2006). Monoterpenes have also been acknowledged to stimulate an increase in anti-inflammatory cytokines, such as IL-10 (Held et al., 2007; M. da S. Lima et al., 2013). In fact, monoterpenes have become a subject of interest in relation to the development of analgesic and anti-inflammatory drugs with an increasing number of new patent applications (de Cássia da Silveira e Sá et al., 2013; Guimarães et al., 2015, 2014; Pina et al., 2017). Monoterpenes are classified into four different types, namely: acyclic (hydrocarbons, alcohols, aldehydes, or esters, especially acetates), monocyclic, bicyclic and iridoid glycosides. Some chemical structures of representative monoterpenes are presented in Fig. 2.
    FPR modulation by essential oil The formyl peptide receptors (FPRs) are chemotactic G protein-coupled receptors which help to control the inflammation, as well as participating in the processes of many pathophysiologic conditions (Dahlgren et al., 2016; Filepa et al., 2018). FPRs were originally discovered as receptors that bind highly conserved N-formyl methionine-containing protein and peptide sequences of bacterial and mitochondrial origin, (Schiffmann et al., 1975), which represent major pro-inflammatory products. Earlier investigations conducted into the expression of FPRs in human cells and tissues showed the immunoreactivity of FPR was observed in hepatocytes, fibroblasts, astrocytes, neurons of the autonomic nervous system, lung and lung carcinoma cells, thyroid, adrenal glands, heart, the tunica media of coronary arteries, endothelial cells, uterus, ovary, testis, placenta, kidney, stomach and colon (Migeotte et al., 2006; Devosse et al., 2009; Shao et al., 2011; Prevete et al., 2015). Recent studies reported that some essential oil components of medicinal plants and products were able to modulate some of these neutrophil functional responses (Schepetkin et al., 2015, 2016). These authors also studied that plant essential oils as a source of novel therapeutics that might be developed to modulate innate immune responses and also enhance defense against microbial infection or control excessive inflammation (Schepetkin et al., 2016). Especially, α-pinene, β-pinene, and terpinen-4-ol, common monoterpenes found in Ferula oils which directly activate [Ca2+]i flux in human neutrophils. In addition, essential oils from Citrus aurantium (bergamot) stimulated ROS production in human neutrophils (Cosentino et al., 2014). Eosinophil migration was inhibited by essential oils from Syzygium cumini and Psidium guajava, which have relatively high levels of β-pinene (Siani et al., 2013). Recently, new chemotactic For-Met-Leu-Phe-OMe (fMLF-OMe) analogues have been synthesized as innovative drugs that act as agonists or/and antagonists of FPRs (Mollica et al., 2006; Torino et al., 2009; Giordano et al., 2004).They can be based on the pharmacophoric groups commonly found in terpenes and other natural products associated with the modulation of inflammatory mediators by tune-up of neutrophil function (Dorward et al., 2015; He and Ye, 2017).