Antioxidant and signal modulation properties of plant polyphenols in controlling vascular inflammation

Kostyuk, Vladimir; Potapovich, Alla I.; Suhan, Tatyana; Luca, Chiara De; Korkina, Liudmila

doi:10.1016/j.ejphar.2011.02.022

Cited by 84 publications

(46 citation statements)

References 54 publications

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“…In fact, several studies reported important activities for verbascoside, including antioxidant and free radical scavenging capacity, neuroprotective, hepatoprotective, analgesic, cytotoxic, antimicrobial, anti-inflammatory and beneficial effects on the cardiovascular system. Most of these activities are also ascribed to isoverbascoside (Fu, Pang, & Wong, 2008;Isacchi et al, 2011;Korkina, 2007;Kostyuk, Potapovich, Suhan, de Luca, & Korkina, 2011;Morikawa et al, 2010). Moreover, it is important to highlight that despite the presence of lower amounts of isoscutellarein derivatives as compared to those of phenylethanoid glycosides, these can also be key components on the ethnopharmacological effects of the plant.…”

Section: Quantification Of Phenolic Compounds In Peelmentioning

confidence: 99%

Phenolic constituents of Lamium album: Focus on isoscutellarein derivatives

Pereira

Domingues

Silva

et al. 2012

Food Research International

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Lamium album L. is an edible plant which is consumed raw or cooked, in particular in the Mediterranean and surrounding areas. It is also consumed as tea infusions and as a main component of food supplements, because of its pharmacological effects. Despite being consumed by humans for centuries, the chemical composition of L. album L. is far from being understood. In this study, a purified ethanolic extract (PEEL) was prepared and further analyzed by high performance liquid chromatography and electrospray mass spectrometry. Overall, verbascoside accounted for approximately half of the phenolic content of the extract, but this also contained other bioactive phenolic compounds herein detected for the first time in the genus, namely isoscutellarein derivatives. The latter included isoscutellarein-7-O-allosyl(1 →2)glucoside, its O-methyl derivative, three acetyl derivatives of isoscutellarein-Oallosyl glucoside and one acetylated form of O-methylisoscutellarein-7-O-allosyl(1 →2)glucoside. From those, the main isoscutellarein derivative was assigned to isoscutellarein-7-O-(6-O-acetyl-β-allosyl)(1→2)-β-glucoside, as confirmed by NMR. Altogether, isoscutellarein derivatives accounted for almost 30% of PEEL phenolics. Since verbascoside and isoscutellarein derivatives are main components of L. album L. ethanolic extract, their possible association to the health benefits of the plant is discussed.

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Section: Quantification Of Phenolic Compounds In Peelmentioning

confidence: 99%

Phenolic constituents of Lamium album: Focus on isoscutellarein derivatives

Pereira

Domingues

Silva

et al. 2012

Food Research International

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“…49,53,54 In addition, many natural products such as resveratrol, EGCG, capsaicin, and curcumin affect AMPK pathways. 55 Other polyphenols also modulate inflammatory pathways 56 , and EGCG modulates FOXO3. 57 IPA revealed that many mRNAs that were significantly regulated by silymarin overlapped with many of the known gene expression changes induced EGCG and curcumin ( Figure 5A).…”

Section: Natural Products That Suppress Inflammation Also Induce Strementioning

confidence: 99%

Silymarin suppresses cellular inflammation by inducing reparative stress signaling

Lovelace¹,

Wagoner²,

Macdonald

et al. 2015

Planta Med

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Silymarin, a characterized extract of the seeds of milk thistle (Silybum marianum), suppresses cellular inflammation. To define how this occurs, transcriptional profiling, metabolomics, and signaling studies were performed in human liver and T cell lines. Cellular stress and metabolic pathways were modulated within 4 h of silymarin treatment: activation of Activating Transcription Factor 4 (ATF-4) and adenosine monophosphate protein kinase (AMPK) and inhibition of mammalian target of rapamycin (mTOR) signaling, the latter being associated with induction of DNA-damage-inducible transcript 4 (DDIT4). Metabolomics analyses revealed silymarin suppression of glycolytic, tricarboxylic acid (TCA) cycle, and amino acid metabolism. Antiinflammatory effects arose with prolonged (i.e. 24 h) silymarin exposure, with suppression of multiple pro-inflammatory mRNAs and signaling pathways including nuclear factor kappa B (NF-* Corresponding Author: (S.J. Polyak). . polyak@uw.edu. Supporting Information. Primer-probe sets for RT-PCR validation of microarray data and antibodies used in Western blotting are in Tables S1 and S2, respectively. Figures S1-S9 provide microarray heat map, microarray RT-PCR validation, protein validation, supporting IPA pinwheels, metabolomics heat map, AMPK knockout validation, and IPA legend. This material is available free of charge via the Internet at http://pubs.acs.org. Author ContributionsThe manuscript was written through contributions of all authors. All authors have given approval to the final version of the manuscript. HHS Public Access Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript κB) and forkhead box O (FOXO). Studies with murine knock out cells revealed that silymarin inhibition of both mTOR and NF-κB was partially AMPK dependent, while silymarin inhibition of mTOR required DDIT4. Other natural products induced similar stress responses, which correlated with their ability to suppress inflammation. Thus, natural products activate stress and repair responses that culminate in an anti-inflammatory cellular phenotype. Natural products like silymarin may be useful as tools to define how metabolic, stress, and repair pathways regulate cellular inflammation.Natural products are used to prevent and treat a plethora of chronic, debilitating, and inflammatory diseases. Over one-third of adults in the US reported self-medicating with complementary and alternative medicines (CAM). 1 Defining precise mechanisms of action is a critical barrier to the optimal application of botanicals as CAMs and as pharmaceuticals. Natural products, like the compounds contained in silymarin (a.k.a. milk thistle extract; from the plant Silybum marianum [L.] Gaertn.[Asteraceae]), protect cells by various antioxidant, anti-inflammatory, antiviral, immunomodulatory, proliferative, and metabolic effects, 2,3 resulting in diverse protective phenotypes, both in vitro and in vivo. For example, silymarin and silymarin-derived flavonolignans inhibit in vitro hepatitis C virus (HCV) infection of hu...

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“…Cellular and molecular investigations further support quercetin's bioactivity in atherosclerosis and suggest that it acts through antioxidant/cytoprotective and anti-inflammatory mechanisms. In vitro, quercetin is a potent reactive oxygen species (ROS) scavenger (Boots et al, 2008); it protects LDL from oxidation (Hayek et al, 1997;Naidu and Thippeswamy, 2002;Leckey et al, 2010) and EC from lipid peroxidation (Kleemann et al, 2011) and prevents redox imbalance (Kostyuk et al, 2011) and endothelin-1-induced dysfunction (Romero et al, 2009). In vivo, quercetin protects against vascular oxidative stress (Loke et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Proatherogenic Macrophage Activities Are Targeted by the Flavonoid Quercetin

Lara-Guzmán

Tabares-Guevara

León-Varela

et al. 2012

J Pharmacol Exp Ther

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Many studies have demonstrated that the flavonoid quercetin protects against cardiovascular disease (CVD) and related risk factors. Atherosclerosis, the underlying cause of CVD, is also attenuated by oral quercetin administration in animal models. Although macrophages are key players during fatty streak formation and plaque progression and aggravation, little is known about the effects of quercetin on atherogenic macrophages. Here, we report that primary bone marrow-derived macrophages internalized less oxidized low-density lipoprotein (ox-LDL) and accumulated less intracellular cholesterol in the presence of quercetin. This reduction of foam cell formation correlated with reduced surface expression of the oxLDL receptor CD36. Quercetin also targeted the lipopolysaccharidedependent, oxLDL-independent pathway of lipid droplet formation in macrophages. In oxLDL-stimulated macrophages, quercetin inhibited reactive oxygen species production and interleukin (IL)-6 secretion. In a system that evaluated cholesterol crystal-induced IL-1␤ secretion via nucleotide-binding domain and leucine-rich repeat containing protein 3 inflammasome activation, quercetin also exhibited an inhibitory effect. Dyslipidemic apolipoprotein E-deficient mice chronically treated with intraperitoneal quercetin injections had smaller atheromatous lesions, reduced lipid deposition, and less macrophage and T cell inflammatory infiltrate in the aortic roots than vehicle-treated animals. Serum levels of total cholesterol and the lipid peroxidation product malondialdehyde were also reduced in these mice. Our results demonstrate that quercetin interferes with both key proatherogenic activities of macrophages, namely foam cell formation and pro-oxidant/proinflammatory responses, and these effects may explain the atheroprotective properties of this common flavonoid.

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Antioxidant and signal modulation properties of plant polyphenols in controlling vascular inflammation

Cited by 84 publications

References 54 publications

Phenolic constituents of Lamium album: Focus on isoscutellarein derivatives

Phenolic constituents of Lamium album: Focus on isoscutellarein derivatives

Silymarin suppresses cellular inflammation by inducing reparative stress signaling

Proatherogenic Macrophage Activities Are Targeted by the Flavonoid Quercetin

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