Phytochemicals as Modulators of Paraoxonase-1 in Health and Diseases

Abstract

Chronic diseases such as cardiovascular disease (CVD), atherosclerosis, chronic liver disease, and neurodegenerative diseases are major causes of mortality. These diseases have gained much attention due to their complications, and therefore novel approaches with fewer side effects are an important research topic. Free radicals and oxidative stress are involved in the molecular mechanisms of several diseases. Antioxidants can scavenge free radicals and mitigate their adverse effects. One of the most important antioxidant enzymes are paraoxonases (PONs). These enzymes perform a wide range of physiological activities ranging from drug metabolism to detoxification of neuroleptics. Paraoxonase-1 (PON1) is produced in the liver and then transferred to the bloodstream. It has been demonstrated that PON1 could have beneficial effects in numerous diseases such as atherosclerosis, CVD, diabetes mellitus, and neurodegenerative diseases by modulating relevant signalling pathways involved in inflammation and oxidative stress. These pathways include peroxisome proliferator-activated receptor gamma (PPAR-γ) and protein kinase B/nuclear factor kappa-light-chain-enhancer of activated B cells (AKT/NF-κB)-dependent signalling pathways. Increasing PON1 could potentially have protective effects and reduce the incidence of various diseases by modulating these signalling pathways. Several studies have reported that dietary factors are able to modulate PON1 expression and activity. This review aimed at summarizing the state of the art on the effects of dietary phytochemicals on PON1 enzyme activity and the relevant signalling pathways in different diseases.

The Role of Polyphenols in Modulating PON1 Activity Regarding Endothelial Dysfunction and Atherosclerosis

“…All of the above are developed by inflammation (TNF-α, IL-1, and IL-6) and oxidative stress. It is well known that antioxidative substances are needed to prevent these pathologies, and it is believed that paraoxonase enzymes have a protective role due to their ability to contribute to antioxidant and anti-inflammatory pathways, especially paraoxonase 1 (PON1) [ 9 , 19 , 20 ].…”

“…PON1 has calcium ions sites; therefore, it needs calcium for activation [ 19 ]. If the calcium is removed, then some of the activities dependent on calcium are inactivated, such as POXase and AREase activity, but the oxidative protection of LDL is still ongoing [ 21 ].…”

Modulatory Effect of Lifestyle-Related, Environmental and Genetic Factors on Paraoxonase-1 Activity: A Review

“…This ultimately results in PKC activation. Polyphenolic compounds can mediate both these pathways [127][128][129][130].…”

The current novel drug delivery system (natural and chemical composites) in dental infections for antibiotics resistance: a narrative review

“…Many diseases have significant influences on the hard and soft tissues of the oral cavity containing congenital anomalies, craniofacial diseases, and diverse infections. Moreover, oral infections have been known to have a main role in the presentation of various inflammatory diseases which have systemic effects, such as pulmonary diseases, cardiovascular diseases, and gastrointestinal disorders (31)(32)(33)(34). Nevertheless, the major clinical disorders that are deemed to be worldwide public health priorities involve oral cancers, osteomyelitis, periodontitis, and PI (7,(35)(36)(37)(38)(39).…”