Differential Protective Effect of Resveratrol and Its Microbial Metabolites on Intestinal Barrier Dysfunction is Mediated by the AMPK Pathway

Zhang, Bowei; Zhang, Yunhui; Liu, Xiaoxia; Yin, Jia; Li, Xiang; Zhang, Xuejiao; Xing, Xiaolong; Wang, Jin; Wang, Shuo

doi:10.1021/acs.jafc.2c04101

Cited by 23 publications

(23 citation statements)

References 67 publications

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“…Resveratrol is a well-known polyphenolic compound extracted at high levels from grape skins, peanuts, blueberries, and the roots of some CHMs, especially Polygonum cuspidatum , Morus alba L., and Panax notoginseng (Burkill) [ 101 , 102 ]. Due to its multiple anti-inflammatory, antioxidant, antitumor, and antimicrobial biological effects, resveratrol has been proven beneficial in various diseases, such as diabetes mellitus, obesity, cancer, and IBD [ 103 , 104 , 105 ]. The antimicrobial activity of resveratrol could impair the homeostasis of gut microbiota.…”

Section: Polyphenols Retard Oxidative Stress and Inflammation Via Mod...mentioning

confidence: 99%

Oxidative Stress, Inflammation, Gut Dysbiosis: What Can Polyphenols Do in Inflammatory Bowel Disease?

Peng

Ding

et al. 2023

Antioxidants

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Inflammatory bowel disease (IBD) is a long-term, progressive, and recurrent intestinal inflammatory disorder. The pathogenic mechanisms of IBD are multifaceted and associated with oxidative stress, unbalanced gut microbiota, and aberrant immune response. Indeed, oxidative stress can affect the progression and development of IBD by regulating the homeostasis of the gut microbiota and immune response. Therefore, redox-targeted therapy is a promising treatment option for IBD. Recent evidence has verified that Chinese herbal medicine (CHM)-derived polyphenols, natural antioxidants, are able to maintain redox equilibrium in the intestinal tract to prevent abnormal gut microbiota and radical inflammatory responses. Here, we provide a comprehensive perspective for implementing natural antioxidants as potential IBD candidate medications. In addition, we demonstrate novel technologies and stratagems for promoting the antioxidative properties of CHM-derived polyphenols, including novel delivery systems, chemical modifications, and combination strategies.

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Section: Polyphenols Retard Oxidative Stress and Inflammation Via Mod...mentioning

confidence: 99%

Oxidative Stress, Inflammation, Gut Dysbiosis: What Can Polyphenols Do in Inflammatory Bowel Disease?

Peng

Ding

et al. 2023

Antioxidants

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“…The main evidence about the potential positive effects of resveratrol for the gut barrier is based on the in vitro studies, which were focused on the changes in the regulatory pathways. The most commonly used cell line was Caco-2 [ 82 , 83 , 84 , 85 ] and intestinal porcine enterocytes (IPEC-J2) [ 86 , 87 ]. The intestinal permeability in these studies was assessed by the measurement of transepithelial electrical resistance (TEER) across the cellular monolayer and by the measurement of the expression of the genes and corresponding proteins.…”

Section: Effect Of Resveratrol On the Gut Barriermentioning

confidence: 99%

“…A recent study evaluated the effect of resveratrol and its metabolites resulting from microbiota metabolism, namely dihydroresveratrol and 3-(4-hydroxyphenyl)-propionic acid on the intestinal barrier in LPS-treated Caco-2 cells [ 85 ]. It was found that only resveratrol and 3-(4-hydroxyphenyl)-propionic acid have beneficial effects on the intestinal barrier by increasing the expression of TJ protein and Muc2, and the molecular mechanism proposed by authors to be involved is monophosphate-activated protein kinase (AMPK)-mediated activation of CDX2 and the regulation of the SIRT1/NF-κβ pathway.…”

Section: Effect Of Resveratrol On the Gut Barriermentioning

confidence: 99%

“…The results obtained in vitro needed confirmation in vivo, especially considering that resveratrol was applied directly on the cell lines, while in vivo the limited bioavailability of phenolic compounds has to be taken into consideration. The majority of studies were performed with rodents including Wistar and Sprague Dawley rats [ 83 , 88 , 89 , 90 , 91 ] and mice [ 85 , 92 , 93 , 94 , 95 , 96 , 97 , 98 ]. One study was performed with ducks [ 99 ].…”

Section: Effect Of Resveratrol On the Gut Barriermentioning

confidence: 99%

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Crosstalk between Resveratrol and Gut Barrier: A Review

Drabińska

Jarocka-Cyrta

2022

IJMS

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The plant-based nutraceuticals are receiving increasing interest in recent time. The high attraction to the phytochemicals is associated with their anti-inflammatory and antioxidant activities, which can lead to reduced risk of the development of cardiovascular and other non-communicable diseases. One of the most disseminated groups of plant bioactives are phenolic compounds. It was recently hypothesized that phenolic compounds can have the ability to improve the functioning of the gut barrier. The available studies showed that one of the polyphenols, resveratrol, has great potential to improve the integrity of the gut barrier. Very promising results have been obtained with in vitro and animal models. Still, more clinical trials must be performed to evaluate the effect of resveratrol on the gut barrier, especially in individuals with increased intestinal permeability. Moreover, the interplay between phenolic compounds, intestinal microbiota and gut barrier should be carefully evaluated in the future. Therefore, this review offers an overview of the current knowledge about the interaction between polyphenols with a special emphasis on resveratrol and the gut barrier, summarizes the available methods to evaluate the intestinal permeability, discusses the current research gaps and proposes the directions for future studies in this research area.

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“…Pinosylvin (PS, 6 ) and dihydropinosylvin (DHP, 7 ) are RSV analogs found mainly in white pines, and DHP is the metabolite of PS by gut microbiota. , 4,4′-Dihydroxystilbene (DHS, 8 ) is a RSV analog found in Yucca periculosa . These RSV analogs and metabolites have many pharmacological activities, including antidiabetic, antitumor, antioxidative, and anti-inflammatory effects. ,, …”

Section: Introductionmentioning

confidence: 99%

Inhibition of Resveratrol Analogs on Human and Rat 3β-Hydroxysteroid Dehydrogenases: Structure–Activity Relationship and Docking Analysis

Su¹,

Tang

et al. 2023

J. Agric. Food Chem.

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Resveratrol and its analogs are phytochemicals. Human 3β-hydroxysteroid dehydrogenase 1 (3β-HSD1) synthesizes steroid hormones for normal pregnancy or promoting cancer metastasis. Whether they inhibit 3β-HSD1 remains unclear. In this study, the inhibitory potency, mode of action, structure−activity relationship, and docking parameters of resveratrol and its analogs on 3β-HSD1 and rat homolog 3β-HSD4 were analyzed. The inhibitory potency of these chemicals on human 3β-HSD1 was 4,4′dihydroxystilbene (IC 50 , 3.68 μM) > pinostilbene (8.07 μM) > pinosylvin (10.60 μM) > lunularin (26.84 μM) > resveratrol (30.20 μM) > dihydroresveratrol (>100 μM) = oxyresveratrol (>100 μM) > dihydropinosylvin (ineffective at 100 μM). Resveratrol analogs and metabolites are mixed or competitive inhibitors of human 3β-HSD1. Resveratrol and 4,4′-dihydroxystilbene inhibited progesterone secretion by human JAr cells at ≥1 μM. Resveratrol (IC 50 , 32.09 μM) and pinosylvin (34.71 μM) significantly inhibited rat placental 3β-HSD4 activity. Docking analysis shows that resveratrol analogs and metabolites bind the steroid-binding sites of human 3β-HSD1 and rat 3β-HSD4 and interact with the catalytic residues Ser125/Thr125 and Tyr155. The negative correlation of LogP and IC 50 values for human 3β-HSD1 indicates that lipophilicity of chemicals plays a critical role in the inhibitory effect of chemicals. In conclusion, 4,4′-dihydroxystilbene, pinostilbene, and pinosylvin effectively inhibit human 3β-HSD1 depending on their lipophilicity, thereby acting as potential therapeutic agents.

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Differential Protective Effect of Resveratrol and Its Microbial Metabolites on Intestinal Barrier Dysfunction is Mediated by the AMPK Pathway

Cited by 23 publications

References 67 publications

Oxidative Stress, Inflammation, Gut Dysbiosis: What Can Polyphenols Do in Inflammatory Bowel Disease?

Oxidative Stress, Inflammation, Gut Dysbiosis: What Can Polyphenols Do in Inflammatory Bowel Disease?

Crosstalk between Resveratrol and Gut Barrier: A Review

Inhibition of Resveratrol Analogs on Human and Rat 3β-Hydroxysteroid Dehydrogenases: Structure–Activity Relationship and Docking Analysis

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