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  • PD 169316 A range of therapies exists

    2020-09-16

    A range of therapies exists for the treatment of inflammation-driven diseases, which can be summarized as non-steroidal anti-inflammatory drugs (NSAIDs), corticoids and steroidal-related drugs (Ward et al., 2008). Despite of these notable PD 169316 successes, there are still major unmet medical needs in the treatment of inflammatory diseases and the development of new anti-inflammatory drugs features, prominently in the research portfolios of most pharmaceutical and biotech companies (Dutra et al., 2016; Ward et al., 2008). Natural products (NPs) continue to be an invaluable source of new chemical entities for the treatment of several diseases, including inflammatory disorders, which are still challenges in the modern medicine, with currently available drugs often not being effective (Dutra et al., 2016; Kondamudi et al., 2013; Li and Vederas, 2009; Suroowan and Mahomoodally, 2018). Flavour and fragrance components common to human diets that have been designated Generally Recognized as Safe (GRAS) by the US Food and Drug Administration (FDA), including terpenes (Juergens, 2014). Monoterpenes are the secondary metabolites of plants with two isoprene units (C5H8), have shown a promising profile as agents that reduce the inflammatory process and also modulate key chemical mediators of the inflammatory cascade, such as cytokines (de Cássia da Silveira e Sá et al., 2013; Juergens, 2014).
    Methods
    Cytokines Cytokines are extracellular proteins with water-soluble mediators released by various cell types and features with dimensions between 8 and 30 kDa that have a fundamental role in communication between cells. They also play an important role in mediating the cross-talk between the nervous and immune systems (Haroon et al., 2012). A large number of PD 169316 produce cytokines in the injured area, including immune cells; they are also produced from the activation of protein kinases activated by mitogens. These polypeptides act through paracrine and autocrine mechanisms, i.e., acting on neighboring cells or on the very cells that produce them, respectively (Lin et al., 2000; Sommer and White, 2010). In the absence of a unified classification system, cytokines were organized by numeric order of discovery as interleukins (numbered from 1 to 35), by functional bioactivity on cells (e.g., tumor necrosis factor [TNF], interferons [IFN], and chemokines), and by functional role in inflammatory response (pro-inflammatory or anti-inflammatory) (Raeburn et al., 2002; Sommer and White, 2010). Based on the functional profile of an immune response, cytokine production is broadly regulated by T helper 1 cells (Th1) which generally mediate a pro-inflammatory cellular immune response and T helper 2 cells (Th2) which enhance anti-inflammatory and humoral immune reactions (Hou et al., 2017). The inflammatory response can be driven by the cytokine production and is certainly a major target in the management of the inflammatory disease. However, hemodynamic homeostasis and metabolic disorders can occur systemically by the overproduction of pro-inflammatory cytokines and low production of anti-inflammatory cytokines (Curfs et al., 1997; Lin et al., 2000). Thus, the inflammatory response is directly influenced by the type of cytokines produced in the microenvironment of the event. Cytokines contribute to restoring tissues after injury through a complex network of interactions able to suppress the inflammatory response. Interleukins (IL) 1, 2, 6, 7 and TNF are examples of cytokines that favor the continuation of inflammation; while IL-10 opposes many of the pro-inflammatory effects of IL-1β and TNF-α (Sommer and White, 2010). Interestingly, cytokines contribute to the status quo of rheumatic but non-inflammatory syndromes such as fibromyalgia (Rodriguez-Pintó et al., 2014). Thus, the anti-inflammatory cytokines are a series of regulatory molecules that can control the pro-inflammatory cytokine response (Verri et al., 2006).