Polyphenols’ role in autoimmune and chronic inflammatory diseases and the advent of computer-driven plant therapies

Abstract

Oxidative stress is caused by an imbalance between reactive oxygen species (ROS) production and their removal via protective mechanisms. This severely contributes to the progression of inflammatory diseases. However, it is resident inflammation that leads to chronic states. To keep homeostasis, pro and anti-inflammatory cytokines modulate signalling cascades to defeat tissue impairment and infection. The underlying processes may cause chronic inflammation, if it remains continuously. Myriad of transcription factors are activated via oxidative stress, triggering protein expression involved in inflammatory pathways. Inflammatory signalling cascades are additionally close related to the establishment of side-conditions (e.g., myocardial infarct, stroke, kidney disease, atherosclerosis, diverse forms of cancer including glioblastoma multiform, and countless age-related ocular illnesses as cataract, glaucoma, diabetic retinopathy, and macular degeneration). To mention one example, atherosclerotic patients suffer from long lasting cholesterol-rich oxidative plaques deposition. To date, several inflammatory biomarkers have been examined, to evidence molecular activity to be targeted in therapeutics-e.g. interleukin families, nuclear factor-kappa B (NfkB), and signal transducer and activator of transcription 3 (STAT3). Polyphenols are anti-oxidative-rich compounds easily introduced in humans’ daily diet, without major investments (polyphenols are found in for instance tea, whole grain wheat, rye, broccoli, asparagus, carrots, coffee, cocoa, olive oil, and red wine). Polyphenols’ antioxidant capacity is demonstrated via their ability to modulate signalling pathways responsible for removing free oxygen and nitrogen species, mitigating the enzymatic promotion of pro-inflammatory activity- e.g. modulating the expression of cyclooxygenase (COX), lipoxygenase (LOX), and inducible nitric oxide synthase (iNOS). Additionally, these hydroxyl-bonded groups of chemical compounds have demonstrated high potential as vasodilators, which can contribute to reducing risk of cardiovascular diseases. Regardless the fact knowledge on polyphenols properties is well-stablished, in the current literature, these properties have been poorly exploited, lacking accurate assessment of polyphenol metabolites as biomarkers (e.g., kaempferol, myricetin, quercetin, naringenin, hesperetin, epicatechin, gallocatechin, epigallocatechin, epicatechingallate, epigallocatechingallate, and procyanidin), among high risk patients, potentially using low risk groups as a control. Additionally, chemical instability of certain herbal medicines combined with needs for improving delivery systems to optimise effectiveness may challenge the success of phytotherapies. Therefore, it urges designing new formulations (e.g., modifying pharmacokinetic profiles) and novel delivery systems that optimise administration routes, e.g. exploiting the low cytotoxicity and biocompatibility of nanoparticles as polysaccharides. To mention one example, hypericin has been tested in photodynamic therapies (precision medicine), due to its photocytotoxic effects inducing apoptosis. Ultimately, computer-assisted approaches may add value by reducing efforts in-production, providing robust tools for pre-laboratorial design and testing. Therefore, in this Chapter, major inflammatory biomarkers will be discussed, limitations and potential of herbal therapies will be presented, and novel therapies debated (including the ones benefitting from computer-aided systems).