Phloretin and its methylglyoxal adduct: Implications against advanced glycation end products-induced inflammation in endothelial cells

Zhou, Qian; Gong, Jun; Wang, Mingfu

doi:10.1016/j.fct.2019.05.004

Cited by 40 publications

(24 citation statements)

References 31 publications

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“…Curcumin along with the other AGE-inhibitor compounds, such as aminoguanidine and phenacylthiazolium compounds, potentially afford therapeutics for the neurodegenerative diseases [53,58]. A polyphenolic component in apple juice, phloretin ( Figure 5), for example, acts as an AGE-inhibitor by sequestrating methylglyoxal, a reactive Maillard reaction intermediate (also formed as a byproduct of glycolysis, lipid peroxidation, and glucose autooxidation) that would lead to protein crosslinking, as demonstrated in the human umbilical endothelial cells (HUVECs) [59]. Dietary polyphenolic compounds undergo extensive catabolism in the colon, forming a variety of small-molecule polyphenolic compounds.…”

Section: Polyphenols As Antiglycating Agentsmentioning

confidence: 99%

Polyphenols in Alzheimer’s Disease and in the Gut–Brain Axis

et al. 2020

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Polyphenolic antioxidants, including dietary plant lignans, modulate the gut–brain axis, which involves transformation of these polyphenolic compounds into physiologically active and neuroprotector compounds (called human lignans) through gut bacterial metabolism. These gut bacterial metabolites exert their neuroprotective effects in various neurodegenerative diseases, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD), and also have protective effects against other diseases, such as cardiovascular diseases, cancer, and diabetes. For example, enterolactone and enterodiol, the therapeutically relevant polyphenols, are formed as the secondary gut bacterial metabolites of lignans, the non-flavonoid polyphenolic compounds found in plant-based foods. These compounds are also acetylcholinesterase inhibitors, and thereby have potential applications as therapeutics in AD and other neurological diseases. Polyphenols are also advanced glycation end product (AGE) inhibitors (antiglycating agents), and thereby exert neuroprotective effects in cases of AD. Thus, gut bacterial metabolism of lignans and other dietary polyphenolic compounds results in the formation of neuroprotective polyphenols—some of which have enhanced blood–brain barrier permeability. It is hypothesized that gut bacterial metabolism-derived polyphenols, when combined with the nanoparticle-based blood–brain barrier (BBB)-targeted drug delivery, may prove to be effective therapeutics for various neurological disorders, including traumatic brain injury (TBI), AD, and PD. This mini-review addresses the role of polyphenolic compounds in the gut–brain axis, focusing on AD.

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Section: Polyphenols As Antiglycating Agentsmentioning

confidence: 99%

Polyphenols in Alzheimer’s Disease and in the Gut–Brain Axis

et al. 2020

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“…It is worth noting that increased efforts are being made to find natural compounds or products to diminish the deleterious effects of AGEs [34,35]. Recent studies have reported the potential antiglycation effects of polyphenols [36][37][38][39][40]. The ethanol extract of finger Italian millet exhibited the most significant inhibition of AGEs formation with IC 50 value of 33.68 ± 5.98 µg/mL as compared with known antiglycation drug, aminoguanidine (IC 50 = 52.30 ± 2.31 µg/mL).…”

Section: Antidiabetic Activity In Vitromentioning

confidence: 99%

Phenolic Profile, Antioxidant, and Antidiabetic Potential Exerted by Millet Grain Varieties

et al. 2020

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This study evaluated the potential antioxidant and antidiabetic properties in vitro of four millet grain varieties cultivated in South Korea. The free fractions were tested for their total antioxidant capacity using 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS+) and 2,2′-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assays, followed by α-glucosidase, α-amylase, and advanced glycation endproducts (AGEs) formation inhibition assays. The total phenolics, flavonoids, and condensed tannins in the free fractions ranged from 107.8 to 136.4 mg ferulic acid equivalent (FAE)/100 g, 101.3 to 115.8 mg catechin equivalent (CE)/100 g, and 17.65 to 59.54 mg catechin equivalent (CE)/100 g, respectively. Finger Italian millet had the highest total phenolic content (136.4 mg FAE/100 g) and flavonoid content (115.8 mg CE/100 g). Barnyard and finger Italian millet showed the highest DPPH (IC50 = 359.6 µg/mL and 436.25 µg/mL, respectively) and ABTS radical scavenging activity (IC50 = 362.40 µg/mL and 381.65 µg/mL, respectively). Similarly, finger Italian millet also exhibited significantly lower IC50 values for the percentage inhibition of α-glucosidase (18.07 µg/mL) and α-amylase (10.56 µg/mL) as compared with acarbose (IC50 = 59.34 µg/mL and 27.73 µg/mL, respectively) and AGEs formation (33.68 µg/mL) as compared with aminoguanidine (AG) (52.30 µg/mL). All eight phenolic compounds identified in finger Italian millet were flavonoids, with flavanols being the predominant subclass. Taken together, millet flavonoids play important roles in the prevention and management of type 2 diabetes, and hence finger Italian millet has the potential to be developed as a functional food.

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“…Natural antioxidants, targeting endothelial cell oxidative stress caused by MGO, are excellent candidates for the prevention of vascular complications in diabetes and delay aging-related tissue dysfunction. For example, the polyphenol phytoantioxidant called phloretin, obtained from apples, can inhibit MGO-induced AGEs formation in human endothelial cells by modifying RAGE/p38 MAPK/NF-κB signaling pathway [ 13 ]. The phenolic compound catechins, commonly found in foods and beverages such as berries, tea, and cocoa, inhibits MGO-induced mitochondrial damage and apoptosis in human endothelial cells [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Unripe Carica papaya Protects Methylglyoxal-Invoked Endothelial Cell Inflammation and Apoptosis via the Suppression of Oxidative Stress and Akt/MAPK/NF-κB Signals

et al. 2021

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Methylglyoxal (MGO), a highly reactive dicarbonyl compound, causes endothelial oxidative stress and vascular complications in diabetes. Excessive MGO-induced ROS production triggers eNOS uncoupling, inflammatory responses, and cell death signaling cascades. Our previous study reported that unripe Carica papaya (UCP) had antioxidant activities that prevented H2O2-induced endothelial cell death. Therefore, this study investigated the preventive effect of UCP on MGO-induced endothelial cell damage, inflammation, and apoptosis. The human endothelial cell line (EA.hy926) was pretreated with UCP for 24 h, followed by MGO-induced dicarbonyl stress. Treated cells were evaluated for intracellular ROS/O2•− formation, cell viability, apoptosis, NO releases, and cell signaling through eNOS, iNOS, COX-2, NF-κB, Akt, MAPK (JNK and p38), and AMPK/SIRT1 autophagy pathways. UCP reduced oxidative stress and diminished phosphorylation of Akt, stress-activated MAPK, leading to the decreases in NF-kB-activated iNOS and COX-2 expression. However, UCP had no impact on the autophagy pathway (AMPK and SIRT1). Although UCP pretreatment decreased eNOS phosphorylation, the amount of NO production was not altered. The signaling of eNOS and NO production were decreased after MGO incubation, but these effects were unaffected by UCP pretreatment. In summary, UCP protected endothelial cells against carbonyl stress by the mechanisms related to ROS/O2•− scavenging activities, suppression of inflammatory signaling, and inhibition of JNK/p38/apoptosis pathway. Thus, UCP shows considerable promise for developing novel functional food and nutraceutical products to reduce risks of endothelial inflammation and vascular complications in diabetes.

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Phloretin and its methylglyoxal adduct: Implications against advanced glycation end products-induced inflammation in endothelial cells

Cited by 40 publications

References 31 publications

Polyphenols in Alzheimer’s Disease and in the Gut–Brain Axis

Polyphenols in Alzheimer’s Disease and in the Gut–Brain Axis

Phenolic Profile, Antioxidant, and Antidiabetic Potential Exerted by Millet Grain Varieties

Unripe Carica papaya Protects Methylglyoxal-Invoked Endothelial Cell Inflammation and Apoptosis via the Suppression of Oxidative Stress and Akt/MAPK/NF-κB Signals

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