Urolithin A ameliorates diabetic retinopathy &lt;i&gt;via&lt;/i&gt; activation of the Nrf2/HO-1 pathway

Xu, Ze-Peng; Li, Songtao; Li, Kunmeng; Wang, Xiaoyu; Li, Xiaojie; An, Meixia; Yu, Xiaoyi; Long, Xinguang; Zhong, Ruiying; Liu, Qiuhong; Wang, Xiaochuan; Yan, Yang; Tian, Ni

doi:10.1507/endocrj.ej21-0490

Cited by 15 publications

(18 citation statements)

References 65 publications

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“…This conclusion was also supported by Lee et al They pointed out that Uro A prevented DM-associated AD by reducing transglutaminase type 2 (TGM2)-dependent mitochondria-associated ER membrane (MAM) formation and maintaining mitochondrial calcium and ROS homeostasis [35]. Xu et al indicated that Uro A ameliorated diabetic retinopathy by activating the Nrf2/HO-1 pathway to inhibit inflammation and oxidative stress [114]. Zhou et al found that Phyllanthus emblica L. facilitated vascular function in STZ-induced hyperglycemia rats by regulating Akt/β-catenin signaling, mediated by the ETs metabolites [115].…”

Section: Protects Pancreatic β Cellsmentioning

confidence: 74%

Ameliorative Effects of Gut Microbial Metabolite Urolithin A on Pancreatic Diseases

Xiao

Bian

et al. 2022

Nutrients

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Urolithin A (Uro A) is a dietary metabolite of the intestinal microbiota following the ingestion of plant-based food ingredients ellagitannins and ellagic acid in mammals. Accumulating studies have reported its multiple potential health benefits in a broad range of diseases, including cardiovascular disease, cancer, cognitive impairment, and diabetes. In particular, Uro A is safe via direct oral administration and is non-genotoxic. The pancreas plays a central role in regulating energy consumption and metabolism by secreting digestive enzymes and hormones. Numerous pathophysiological factors, such as inflammation, deficits of mitophagy, and endoplasmic reticulum stress, can negatively affect the pancreas, leading to pancreatic diseases, including pancreatitis, pancreatic cancer, and diabetes mellitus. Recent studies showed that Uro A activates autophagy and inhibits endoplasmic reticulum stress in the pancreas, thus decreasing oxidative stress, inflammation, and apoptosis. In this review, we summarize the knowledge of Uro A metabolism and biological activity in the gut, as well as the pathological features and mechanisms of common pancreatic diseases. Importantly, we focus on the potential activities of Uro A and the underlying mechanisms in ameliorating various pancreatic diseases via inhibiting inflammatory signaling pathways, activating autophagy, maintaining the mitochondrial function, and improving the immune microenvironment. It might present a novel nutritional strategy for the intervention and prevention of pancreatic diseases.

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Section: Protects Pancreatic β Cellsmentioning

confidence: 74%

Ameliorative Effects of Gut Microbial Metabolite Urolithin A on Pancreatic Diseases

Xiao

Bian

et al. 2022

Nutrients

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“…Urolithin A at a concentration of 10 µM on high glucose-induced human retinal endothelial (HRE) cells counteracted the oxidative stress, increasing SOD activity and GSH levels and reducing MDA, IL-6, IL-1β, and TNF-α levels and gene expression [152]. The Urolithin A and urolithin B modulate oxidative stress and are recognized as emerging antioxidant coumarin derivatives, reducing ROS generation, free radical scavenging, and activating the Nrf2 signaling pathway through Nrf2 nuclear translocation with further upregulation of HO-1, SOD, glutathione-related antioxidant system, and NQO1 [148].…”

Section: Intestinal Anti-inflammatory Gut Microbial Coumarins Targeti...mentioning

confidence: 99%

“…The Urolithin A and urolithin B modulate oxidative stress and are recognized as emerging antioxidant coumarin derivatives, reducing ROS generation, free radical scavenging, and activating the Nrf2 signaling pathway through Nrf2 nuclear translocation with further upregulation of HO-1, SOD, glutathione-related antioxidant system, and NQO1 [148]. The antioxidant properties of urolithin A and urolithin B were related to the control of several diseases such as diabetes, skin aging, sclerosis, kidney and liver toxicity, inflammation, and osteoclastogenesis [152][153][154][155][156][157][158][159].…”

Section: Intestinal Anti-inflammatory Gut Microbial Coumarins Targeti...mentioning

confidence: 99%

Natural Coumarin Derivatives Activating Nrf2 Signaling Pathway as Lead Compounds for the Design and Synthesis of Intestinal Anti-Inflammatory Drugs

Stasi

2023

Pharmaceuticals

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Nrf2 (nuclear factor erythroid 2-related factor 2) is a transcription factor related to stress response and cellular homeostasis that plays a key role in maintaining the redox system. The imbalance of the redox system is a triggering factor for the initiation and progression of non-communicable diseases (NCDs), including Inflammatory Bowel Disease (IBD). Nrf2 and its inhibitor Kelch-like ECH-associated protein 1 (Keap1) are the main regulators of oxidative stress and their activation has been recognized as a promising strategy for the treatment or prevention of several acute and chronic diseases. Moreover, activation of Nrf2/keap signaling pathway promotes inhibition of NF-κB, a transcriptional factor related to pro-inflammatory cytokines expression, synchronically promoting an anti-inflammatory response. Several natural coumarins have been reported as potent antioxidant and intestinal anti-inflammatory compounds, acting by different mechanisms, mainly as a modulator of Nrf2/keap signaling pathway. Based on in vivo and in vitro studies, this review focuses on the natural coumarins obtained from both plant products and fermentative processes of food plants by gut microbiota, which activate Nrf2/keap signaling pathway and produce intestinal anti-inflammatory activity. Although gut metabolites urolithin A and urolithin B as well as other plant-derived coumarins display intestinal anti-inflammatory activity modulating Nrf2 signaling pathway, in vitro and in vivo studies are necessary for better pharmacological characterization and evaluation of their potential as lead compounds. Esculetin, 4-methylesculetin, daphnetin, osthole, and imperatorin are the most promising coumarin derivatives as lead compounds for the design and synthesis of Nrf2 activators with intestinal anti-inflammatory activity. However, further structure–activity relationships studies with coumarin derivatives in experimental models of intestinal inflammation and subsequent clinical trials in health and disease volunteers are essential to determine the efficacy and safety in IBD patients.

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“…Intestinal microorganisms metabolize ellagic acid from raspberry to produce urolithin A, which stimulates nuclear NRF2 and HO-1 levels both in vivo and in vitro, activating the NRF2/HO-1 pathway. 59 Ellagic acid/ urolithin has been shown to have good potential in treating ROS-induced neurodegeneration by reducing oxidative stress and preventing inflammation.…”

Section: Food and Function Reviewmentioning

confidence: 99%

Raspberry polyphenols alleviate neurodegenerative diseases: through gut microbiota and ROS signals

Shi

et al. 2023

Food Funct.

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Urolithin A ameliorates diabetic retinopathy <i>via</i> activation of the Nrf2/HO-1 pathway

Cited by 15 publications

References 65 publications

Ameliorative Effects of Gut Microbial Metabolite Urolithin A on Pancreatic Diseases

Ameliorative Effects of Gut Microbial Metabolite Urolithin A on Pancreatic Diseases

Natural Coumarin Derivatives Activating Nrf2 Signaling Pathway as Lead Compounds for the Design and Synthesis of Intestinal Anti-Inflammatory Drugs

Raspberry polyphenols alleviate neurodegenerative diseases: through gut microbiota and ROS signals

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