Role of polyphenols and polyphenol-rich foods in the modulation of PON1 activity and expression

Abstract

27Paraxonase 1 (PON1) is a HDL-associated enzyme involved in the protection of LDL and HDL-28 lipoproteins against lipid peroxidation. Several studies documented the capacity of polyphenols 29 to stimulate PON1 transcription activation. 30The objective of the present review is to provide the main evidence about the role and the 31 potential mechaninsm of action of polyphenols and polyphenol-rich foods in the modulation of 32 PON1 gene expression and activity. 33A total of 76 in vitro and in vivo studies were included in the review. Overall, while evidence 34 obtained in vitro are limited to quercetin and resveratrol, those deriving from animal models 35 seem more convincing for a wide range of polyphenols but only at pharmacological doses. 36Evidence from human studies are promising but deserve more substantiation about the role of 37 polyphenol-rich foods in the regulation of PON1 activity and expression. 38Research focused on the understanding of the structure-activity relathionship of polyphenols 39 with PON1 and on the mechanisms at the base of PON1-modulation is warranted. designed human intervention studies are encourage to corroborate the findings of polyphenols 41 also at physiological doses. 63Several studies support the hypothesis that a low paraxonase and lactonase activity of 64 PON1 has been associated with an increased oxidative stress and vulnerability to plaque 65 formation, atherosclerosis and cardiovascular diseases [1,[4][5][6][7][8][9] that polyphenols effects may be mediated also by the regulation of PON1 activity and gene 96 expression. In the present review, we attempt to summarize the main evidence on the potential 97 effects of polyphenols and polyphenol-rich foods on PON1 expression and activity also 98 considering, when available, the contribution of genetic factors and the mechanisms of action. 99The review will focus on both in vitro and in vivo studies. 100 2.OVERVIEW OF IN VITRO AND IN VIVO STUDIES ON POLYPHENOLS AS 101 MODULATORS OF PON1 EXPRESSION AND ACTIVITY 102A systematic search for literature focused on the effect of polyphenols and polyphenol-rich found the optimal induction of intracellular and extracellular PON1 activity within 2-20 μM of 141 resveratrol while no effect was observed at doses higher than 20 μM, which in turn resulted 142 cytotoxic leading to a decrease of cell metabolic activity. 143Three studies found a dose-dependent in increase of PON1 activity [42,45,46] Animal studies 167The effect of polyphenols and polyphenol-rich foods on animal models has been evaluated in 44 168 studies (see Supplementary Table 2 under "Supplemental data" in the online issue) 169 [25,39,40,42,43,. Most of them were performed on mice or rats, while two studies on 170 hamsters [62,74]. The main polyphenols tested were quercetin [43,52,54,58,63,68,71,87] [25,53,56,57,69,70,78,85,87]. Other studies provided only an estimation 176 of the polyphenol content evaluated through indirect techniques, for example measuring the total 177 phenolic content by the Folin-Ciocalt...

Anthocyanin-rich Buni-berry (Antidesma bunius) Extract Increases Paraoxonase 1 Gene Expression in BALB/c Mice Fed with a High-fat Diet

“…The effect of polyphenols on PON expression and activity could effectively be detected if the duration of the intervention is at least 12 weeks. 9 In our study, the effect that was resulted from the buni berry extract on PON1 expression was comparable to those with simvastatin, a typical lowering cholesterol drug. Statins modulate expression of PON1 gene through the interaction of sterol regulatory element binding protein (SREBP-2) with Sp1 24 and mitogen-activated protein kinase (MAPK) signaling cascade.…”

“…Several study in animals and human have provided evidences that polyphenolic compounds from several different fruit and plant components have increased PON1 mRNA expression and PON1 concentration. 9 In daily life, free radicals from internal body metabolisms and from outer environments can cause lipid oxidation as the initial process of atherosclerosis. PON 1 enzyme as a protein component of HDL prevents HDL and LDL from oxidation.…”

“…6 Studies by Litvinov et al 7 and Lusis et al 8 have revealed that PON1 as protein and hydrolyzing enzyme responsible for the most of the antioxidant properties of HDL which prevent LDL and HDL from oxidation. Martini et al 9 reported in their review that polyphenolic compounds from fruits and other part of plants can increase expression of PON1 mRNA and concentration of PON1 enzyme. The aim of our study was to demonstrate whether buni-berry (Antidesma bunius) extract can increase mRNA expression of PON1 in balb/c mice fed with a high-fat diet.…”

Phenotypes and concentration of PON1 in cardiovascular disease: The role of nutrient intake

“…Serum PON1 activity can vary up to 40-fold between individuals, and differences in PON1 concentration can vary up to 13 times [7]. In this regard, it has been shown that PON1 activity is affected by genetic polymorphisms (Leu/Met at position 55 and Arg/Glu at position 192), environmental factors, age, sex, lifestyle, pharmaceutical drugs, and dietary factors [8,9]. In the case of the latter, it has been observed that pro-atherogenic diets have been related to a significant decrease in PON1 activity or concentration [10].…”

Discovering the health promoting potential of fermented papaya preparation- its future perspectives for the dietary management of oxidative stress during diabetes

“…While on a broader scale, components of the Carica papaya have been found to decrease serum glucose, trigylcerides and transaminases in STX-induced diabetic rats [76] and positively influence vascular functions and reduce insulin resistance in human subjects [77], plants of similar characteristics have been listed as potential herbal therapies in diabetes patients [78]. Studies by Martini et al [79] have shown the ability of polyphenols in upregulating the transcriptional activity of paraoxonase I (PON1), potentially via its protective effects against oxidative stress-induced inactivation, hence altering the pathophysiological processes of diabetes. Other intricate mechanisms have associated polyphenols to improved insulin sensitivity via AMPK activation and modulation of energy sensors [80]; downregulation of mIRNA-335 expression to improve insulin signalling and lipid metabolism via disinhibition of genes such as InsR, Irs1, Sirt1, Prkaa1, Ppargc1a, Ppara, Lpl, Foxo1 and Gsk3b [81]; and modification of the circadian circuitry via Cry1 and Bmal1 genes to enhance insulin sensitivity and regulate glucose homeostasis respectively [82].…”