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Bladder and Prostate Cancer
Published in Spyridon E. Kintzios, Maria G. Barberaki, Evangelia A. Flampouri, Plants That Fight Cancer, 2019
Charlie Khoo, Yiannis Philippou, Marios Hadjipavlou, Abhay Rane
These results do not correlate with the early results available from randomized trials. Freedland et al. conducted a double-blind, randomized study of 70 men due to undergo radical prostatectomy. Participants received either pomegranate extract (POMx, Pom Wonderful, Los Angeles, CA) or placebo daily for four weeks prior to surgery. Resected samples were analyzed for intra-prostatic Urolithin A (a pomegranate metabolite), 8-oxo-2¢-deoxyguanosine (a major marker of oxidative stress), pS6 kinase and NF-κB (biomarkers of prostate cancer inflammation, development, and progression), and Ki-67 (a biomarker of cell proliferation). Urolithin A was detected in 21/33 in the treatment group, and 12/35 in the control (P = 0.031). Although POMx was associated with 16% lower benign tissue 8-OHdG, this was not significant. There were no differences between treatment and control groups in levels of other biomarkers (Freedland et al. 2013).
Nutrition and the Risk of Common Forms of Cancer
Published in David Heber, Zhaoping Li, Primary Care Nutrition, 2017
Moreover, in a study in human volunteers published in 2015, our group demonstrated that administration of pomegranate juice altered gut microbial populations and increased those producing urolithin A in individuals who were urolithin producers (Li et al. 2015). Based on urinary measurement of urolithin A, about 70% of normal subjects are producers and 30% are nonproducers. Some nonproducers can be induced to produce urolithin A through repeated administration of pomegranate juice daily for 28 days. Ongoing research is examining aspects of this phenomenon, but pomegranate polyphenols in common with green tea and cranberry juice appear to have polyphenols that change gut microbiota.
Free Radicals and Antioxidants
Published in Chuong Pham-Huy, Bruno Pham Huy, Food and Lifestyle in Health and Disease, 2022
Chuong Pham-Huy, Bruno Pham Huy
(ETs) and ellagic acid (EA) are polyphenols present in some fruits (raspberry, blackberry, strawberry, pomegranate), nuts (walnut, almond), and seeds (181–182). Ellagitannins (esters of hexahydroxydiphenoic acid and glucose) are slowly hydrolyzed in the digestive tract, releasing ellagic acid (EA). ETs and EA form a diverse group of bioactive polyphenols with antioxidant, anticancer, anti-inflammatory, and antimicrobial (antibacterial, antifungal and antiviral) activities. Moreover, they improve the health of blood vessels (181–182). ETs and EA are then gradually metabolized by the gut microbiota of different mammals to produce different types of urolithins (A, B, C, D) during the metabolism of non-absorbed nutrients containing ellagitannins and ellagic acid. Urolithins are then incorporated into enterohepatic circulation. Urolithins are important bioactive compounds which can play the role of hormone analogs (181). Urolithins could display estrogenic and/or anti-estrogenic activity and tissue disposition studies reveal that urolithins are enriched in prostate, intestinal, and colon tissues in mice, which could explain why urolithins inhibit prostate and colon cancer cell growth (182). Moreover, antiproliferative and apoptosis-inducing activities of EA and urolithins have been demonstrated by the inhibition of cancer cell growth (182). Urolithin A (UA) is a first-in-class natural food metabolite of ETs that stimulates mitophagy and prevents the accumulation of dysfunctional mitochondria with age, thereby maintaining mitochondrial biogenesis and respiratory capacity in cells (183). Recently, urolithin A (UA) is shown to stimulate mitophagy and improve muscle health in old animals and in preclinical models of aging. These observed effects on mitochondrial biomarkers show that UA induces a molecular signature of improved mitochondrial and cellular health following regular oral consumption of UA in humans (183). UA could be a promising anti-aging compound.
Punicalagin attenuates ventricular remodeling after acute myocardial infarction via regulating the NLRP3/caspase-1 pathway
Published in Pharmaceutical Biology, 2023
Jian-fei Peng, Xiao-ni Zhao, Meng Zhang, Jing-ya Li, Chun-chun Zhao, Shu-shu Wang, Jia-li Wang, Hui Shi, Peng Zhou, Liang Wang
In this study, molecular docking prediction revealed that punicalagin may act on NLRP3. In vivo pharmacodynamics studies showed that punicalagin could improve hemodynamics and cardiac function, alleviate myocardial fibrosis and reduce myocardial cell apoptosis. Moreover, punicalagin could inhibit the expression of key proteins and genes in the NLRP3/Caspase-1 signaling pathway using immunohistochemistry, RT-PCR and Western blotting. The results suggested that punicalagin can prevent and treat VR after AMI, and the protective effect is related to its regulatory NLRP3/Caspase-1 signaling pathway. However, urolithin A, as a metabolite of punicalagin, has good effects on preventing and treating myocardial fibrosis, and anti-inflammatory activity (Chen et al. 2022; Hering et al. 2021). Further mechanism studies found that urolithin A has a good effect on inhibiting NLRP3, mainly reflected in mitigating STING-NLRP3 axis-mediated inflammatory response by promoting Parkin-dependent mitophagy (Zhang et al. 2022), and activating the AMPK and autophagy to inhibit the endoplasmic reticulum stress-related TXNIP/NLRP3/IL-1β signaling pathway (Zhang et al. 2021). Since punicalagin and its metabolite urolithin A both have good myocardial protection and inhibition of NLRP3 activity, in the future experiment, in-depth study will be conducted at the cellular level to clarify the substances.
Pomegranate peel polyphenols interaction with intestinal flora and its metabolic transformation
Published in Xenobiotica, 2022
Haidan Shi, Junqi Yang, Jianke Li
Based on the above results, it implies that may be two main stages in the metabolic transformation of pomegranate peel polyphenols (Figure 5). In the first stage, during the first 3 weeks, the main metabolites present in biological fluids are those derived from punicalagin by hydrolysis and further conjugation (methyl ethers or glucuronic acid derivatives) (Gil-Izquierdo et al. 2002). Since then, different urolithins were produced in the gut starting with tetrahydroxy-urolithin through the removal of one of the lactone rings of ellagic acid, and by sequential removal of hydroxyls to end with Urolithins A (Landete 2011; Espín et al. 2013). It was deduced that such changes may be related to the intestinal flora in faeces. The Urolithin A content in faeces of rats in group C of antibiotic intervention increased significantly, and it was proportional to time. The increase of Urolithin A in faeces of rats in group C was consistent with the decrease of it in urine.
Is anti-ageing drug discovery becoming a reality?
Published in Expert Opinion on Drug Discovery, 2020
Urolithin A occurs through the influence of microbiota on ellagic acid, a component of polyphenolic-rich plant foods, which stimulates mitophagy and improves muscle health in old animals. It also increases lifespan in C. elegans and in old mice [27]. Urolithin A demonstrates safety and bioavailability in elderly people, while it modulates acylcarnitines in plasma and the expression of skeletal muscle mitochondria genes, that researchers believe can help to treat sarcopenia [28].