Natural Compounds as Modulators of NADPH Oxidases

Abstract

Reactive oxygen species (ROS) are cellular signals generated ubiquitously by all mammalian cells, but their relative unbalance triggers also diseases through intracellular damage to DNA, RNA, proteins, and lipids. NADPH oxidases (NOX) are the only known enzyme family with the sole function to produce ROS. The NOX physiological functions concern host defence, cellular signaling, regulation of gene expression, and cell differentiation. On the other hand, increased NOX activity contributes to a wide range of pathological processes, including cardiovascular diseases, neurodegeneration, organ failure, and cancer. Therefore targeting these enzymatic ROS sources by natural compounds, without affecting the physiological redox state, may be an important tool. This review summarizes the current state of knowledge of the role of NOX enzymes in physiology and pathology and provides an overview of the currently available NADPH oxidase inhibitors derived from natural extracts such as polyphenols.

Enhanced task-related brain activation and resting perfusion in healthy older adults after chronic blueberry supplementation

“…There is evidence from in vitro studies that polyphenols induce activation of endothelial NO synthase via signalling through Estrogen Receptor-␣ via G protein, ERK and PI3K pathways (Chalopin et al 2010). In addition, polyphenols have been shown to inhibit nicotinamide adenine dinucleotide phosphate oxidase, one of the key sources of superoxide production (Maraldi 2013), and to induce signalling through Nrf2 thus increasing endogenous antioxidant capacity (Ramirez-Sanchez et al 2013); both of these will preserve NO bioavailability by reduced formation of peroxynitrite from the reaction of NO and superoxide. In the present study, glutathione status declined in both conditions across the 12-week study.…”

“…A group of polyphenols known as flavonoids, which are highly abundant in plants , are likely to be important bioactive components contributing to these favourable effects. Flavonoids encompass a range of subclasses including anthocyanins, flavonones, flavanols, flavonols, flavones, isoflavones, and proanthocyanidins that possess in vivo anti-oxidant and anti-inflammatory properties Maraldi 2013;Del Rio et al 2013). Higher flavonoid intake is associated with an attenuated rate of cognitive decline over a 10-year period in healthy adults (Letenneur et al 2007).…”

Upregulation of NOX2 and NOX4 Mediated by TGF-β Signaling Pathway Exacerbates Cerebral Ischemia/Reperfusion Oxidative Stress Injury

“…The major ROS involved in oxidative stress include superoxide anion, hydrogen peroxide, and hydroxyl radicals [20]. Multiple sources and processes lead to ROS generation in cells, such as NOX, nitric oxide synthase, cytochrome P-450, cyclooxygenase, lipoxygenase, and xanthine oxidase [21, 22]; however, NOX is considered the primary enzyme responsible for ROS generation. To date, seven subtypes of NOX have been found in rats, namely, NOX1-NOX5, dual oxidase 1 (DUOX1), and DUOX2, but only NOX2 and NOX4 were demonstrated as the major types involved in brain tissue ROS generation.…”

Inherent Oxidative Stress in the Lewis Rat Is Associated with Resistance to Toxoplasmosis

“…This implied that the LEW rat maintained cellular microenvironmental oxidative stress which it is able to tolerate. During microbial invasion, immune effector cells, including neutrophils, eosinophils, and macrophages, have been shown to generate an oxidative burst that is toxic to the invading pathogen (19,24).…”