Pleiotropic Biological Effects of Dietary Phenolic Compounds and their Metabolites on Energy Metabolism, Inflammation and Aging

Abstract

Dietary phenolic compounds are considered as bioactive compounds that have effects in different chronic disorders related to oxidative stress, inflammation process, or aging. These compounds, coming from a wide range of natural sources, have shown a pleiotropic behavior on key proteins that act as regulators. In this sense, this review aims to compile information on the effect exerted by the phenolic compounds and their metabolites on the main metabolic pathways involved in energy metabolism, inflammatory response, aging and their relationship with the biological properties reported in high prevalence chronic diseases. Numerous in vitro and in vivo studies have demonstrated their pleiotropic molecular mechanisms of action and these findings raise the possibility that phenolic compounds have a wide variety of roles in different targets.

Keywords: aging; bioactive compounds; chronic disorders; inflammation; metabolites; oxidation; phenolic compounds; pleiotropic.

Figure 1

Molecular signaling pathways that are activated or inactivated by dietary phenolics or their metabolites in oxidative stress, inflammation process, and aging. SM: Silybum marianum; LC: Lippia citriodora; HS: Hibiscus sabdariffa; TC: Theobroma cacao; OE: Olea europaea; AMPK: AMP-activated protein kinase; mTOR: the mammalian target of rapamycin; ATP: Adenosine triphosphate; AMP: Adenosine monophosphate; ROS: Reactive oxygen species; LKB1: liver kinase B1; CaMKK β: Ca2⁺/calmodulin-dependent protein kinase β; SIRT1: Sirtuin 1; ACC: Acetyl-CoA carboxylase; FAS: Fatty acid synthase; NF-kB: Nuclear factor-κB; IKKβ: IĸB kinase; COX-2: Cyclooxygenase-2; Akt: Protein kinase B; PI3K: Fosfoinositol 3-quinasa; Keap1: Kelch-like ECH-associated protein; Nrf2: Nuclear factor-erythroid 2 p45-related factor 2; MEK 1/2: Mitogen-activated protein kinase 1/2; ERK 1/2: Extracellular signal-regulated kinase 1/2; GPCR: G protein-coupled receptor; IGF-R: Insulin-like growth factor receptor; IR: Insulin receptor; ARE: Antioxidant response element; HO-1: Heme oxygenase 1; CO: Carbon monoxide; C/EBP-α: CCAAT/enhancer-binding protein α; PPAR-γ: Proliferator Peroxisome Activated Receptor-γ; SREBP-1c: Sterol regulatory element-binding protein-1c; IL-1: Interleukin-1; IL-6: Interleukin-6; TNF-α: Tumor necrosis factor α. Thin green arrows indicate the activation of a molecule; thin red lines indicate the inactivation of a molecule; thick green arrows indicate the promotion of a process; thick red lines indicate the reduction of a process; thick orange lines indicate the translocation of molecules.