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Nature has been a rich source of pharmaceutical compounds, producing 80% of our currently prescribed drugs. The feijoa plant, Acca sellowiana , is classified in the family Myrtaceae, native to South America, and currently grown worldwide to produce feijoa fruit. Feijoa is a rich source of bioactive compounds with anticancer, anti-inflammatory, antibacterial, and antifungal activities; however, the mechanism of action of these compounds is largely not known. Here, we used chemical genetic analyses in the model organism Saccharomyces cerevisiae to investigate the mechanism of action of a feijoa-derived ethanol adduct of vescalagin (EtOH-vescalagin). Genome-wide barcode sequencing analysis revealed yeast strains lacking genes in iron metabolism, zinc metabolism, retromer function, or mitochondrial function were hypersensitive to 0.3 µM EtOH-vescalagin. This treatment increased expression of iron uptake proteins at the plasma membrane, which was a compensatory response to reduced intracellular iron. Likewise, EtOH-vescalagin increased expression of the Cot1 protein in the vacuolar membrane that transports zinc into the vacuole to prevent cytoplasmic accumulation of zinc. Each individual subunit in the retromer complex was required for the iron homeostatic mechanism of EtOH-vescalagin, while only the cargo recognition component in the retromer complex was required for the zinc homeostatic mechanism. Overexpression of either retromer subunits or high-affinity iron transporters suppressed EtOH-vescalagin bioactivity in a zinc-replete condition, while overexpression of only retromer subunits increased EtOH-vescalagin bioactivity in a zinc-deficient condition. Together, these results indicate that EtOH-vescalagin bioactivity begins with extracellular iron chelation and proceeds with intracellular transport of zinc via the retromer complex. More broadly, this is the first report of a bioactive compound to further characterize the poorly understood interaction between zinc metabolism and retromer function. [ABSTRACT FROM AUTHOR]

The Quercus genus (oaks) comprises valuable plant resources that are used in many fields, including cosmetics, foods, and pharmaceuticals. Nonetheless, overall chemical profiling and anti-glycation component identification have not been thoroughly performed. In the present study, 70 % ethanolic and water extracts from three oak species (Quercus dentata, Q. serrata, and Q. aliena) showed antioxidant and anti-glycation potential. Thus, the components of the three oak species were profiled using ultra-performance liquid chromatography coupled with electrospray ionization and quadrupole time-of-flight mass spectrometry. The analysis showed that phenolic acids, ellagitannins, ellagic acid, procyanidin, and flavonoid (quercetin, myricetin, kaempferol, isorhamnetin, and taxifolin) glycosides are the main phenolic compounds. Based on the fluorescence assay, they act as strong inhibitors of non-enzymatic advanced glycation end-products (AGEs) formation in the bovine serum albumin (BSA) and skin proteins (collagen and elastin). Furthermore, mass fragmentation analysis demonstrated that ellagitannin, procyanidin B1 and flavonoid glycosides effectively trapped methylglyoxal (MGO), a reactive carbonyl intermediate and an important precursor of AGEs, to generate mono-, di-, or tri-MGO. Collectively, ellagic acid, ellagitannins, procyanidin B1, and flavonoid glycosides, the main active ingredients of three oak species (Q. dentata, Q. serrata, and Q. aliena), may be employed as lead structures in the development of functional foods or drugs to prevent diseases caused by aging and excessive sugar consumption.

This study compared the efficacy of aqueous extracts of commercially available pomegranate peel products and a juice powder in inhibiting the growth of two enterohemorrhagic Escherichia coli strains. Cell suspension of each E. coli strain (5 Log CFU/ml) was added into tryptic soy broth amended with 9 or 23% of each extract prepared with two different methods. After treatment for 5, 10, and 24 h at 25 °C, surviving E. coli cells were enumerated on tryptic soy agar to determine cell population reduction compared to the controls. The concentrations of six different ellagitannins and titratable activity in each treatment system were determined and correlated to E. coli cell population reduction. The extracts from three powdered pomegranate peels caused a significantly greater (p ≤ 0.05) reduction in E. coli population than the extract from the whole peel and juice powder. The higher dose of extracts resulted in a greater cell population reduction than the lower dose. The level of E. coli population reduction correlated positively with the total ellagitannins content (R2 0.67–0.98) and the titratable acidity (R2 0.69–0.98) in the treatment systems. The study suggests that pomegranate peels are promising natural additives or preservatives to control pathogens like EHEC.

Objective: To investigate the effect of ellagic acid on the growth indices and leaf aging process in soybean, an experiment was conducted during the two years of 2018 and 2019 in the research farm of Shahrood University of Technology's Faculty of Agriculture. Method: The experiment was carried out factorial in the form of a randomized complete block design in three replications. The experimental treatments include the initial seed quality at two levels (normal seeds and aged seeds) and the application of ellagic acid at four levels (control, priming, foliar spraying and combined application of priming and foliar spraying with a concentration of 50 mg/L). Results: Accelerated aging caused a reduction of 37.93 and 39.93 percent of emergence. Ellagic acid as priming in aging conditions caused an increase of 11.33 and 8.33 percent of this trait. Aging decreased the amount of chlorophyll, carotenoid, plant height, and leaf and stem dry weight, oil percentage and seed yield. The use of ellagic acid in the form of priming, foliar spraying and their combination in this study increased the percentage of oil by 0.23, 0.24 and 0.29%, respectively, compared to the control. Priming, foliar spraying and the combined application of priming and foliar spraying with ellagic acid improved the grain yield by 23.59, 23.23 and 55.48%, respectively. Conclusion: The use of ellagic acid as seed priming and foliar spraying better than other levels. Finally, it is recommended to use this material as a priming to increase the percentage of oil and yield of soybean. [ABSTRACT FROM AUTHOR]

A complex metabolic disorder, type 2 diabetes, was investigated to explore the impact of ellagitannin, derived from Rosa roxburghii Tratt (RTT), on liver lipid metabolism disorders in db/db mice. The findings demonstrated that both RTT ellagitannin (C1) and RTT ellagic acid (C4) considerably decelerated body mass gain in db/db mice, significantly decreased fasting blood glucose (FBG) levels, and mitigated the aggregation of hepatic lipid droplets. At LDL-C levels, C1 performed substantially better than the C4 group, exhibiting no significant difference compared to the P (positive control) group. An RNA-seq analysis further disclosed that 1245 differentially expressed genes were identified in the livers of experimental mice following the C1 intervention. The GO and KEGG enrichment analysis revealed that, under ellagitannin intervention, numerous differentially expressed genes were significantly enriched in fatty acid metabolic processes, the PPAR signaling pathway, fatty acid degradation, fatty acid synthesis, and other lipid metabolism-related pathways. The qRT-PCR and Western blot analysis results indicated that RTT ellagitannin notably upregulated the gene and protein expression levels of peroxisome proliferator-activated receptor alpha (PPARα) and peroxisome proliferator-activated receptor gamma (PPARγ). In contrast, it downregulated the gene and protein expression levels of sterol regulatory element-binding protein (SREBP), recombinant fatty acid synthase (FASN), and acetyl-CoA carboxylase (ACC). Therefore, RTT ellagitannin can activate the PPAR signaling pathway, inhibit fatty acid uptake and de novo synthesis, and ameliorate hepatic lipid metabolism disorder in db/db mice, thus potentially aiding in maintaining lipid homeostasis in type 2 diabetes. [ABSTRACT FROM AUTHOR]

Foods rich in ellagic tannins are first hydrolyzed into ellagic acid in the stomach and small intestine, and then converted into urolithins with high bioavailability by the intestinal flora. Urolithin has beneficially biological effects, it can induce adipocyte browning, improve cholesterol metabolism, inhibit graft tumor growth, relieve inflammation, and downregulate neuronal amyloid protein formation via the β3-AR/PKA/p38MAPK, ERK/AMPKα/SREBP1, PI3K/AKT/mTOR signaling pathways, and TLR4, AHR receptors. But differences have been reported in urolithin production capacity among different individuals. Thus, it is of great significance to explore the biological functions of urolithin, screen the strains responsible for biotransformation of urolithin, and explore the corresponding functional genes. Tannin acyl hydrolase can hydrolyze tannins into ellagic acid, and the genera Gordonibacter and Ellagibacter can metabolize ellagic acid into urolithins. Therefore, application of "single bacterium", "single bacterium + enzyme", and "microflora" can achieve biotransformation of urolithin A. In this review, the source and metabolic pathway of ellagic tannins, and the mechanisms of the biological function of a metabolite, urolithin A, are discussed. The current strategies of biotransformation to obtain urolithin A are expounded to provide ideas for further studies on the relationship between urolithin and human health. [ABSTRACT FROM AUTHOR]

Stachyurin and casuarinin are ellagitannins, a class of polyphenols that exhibit various biological activities that have an impact on human health. Casuarinin is a stachyurin stereoisomer. These compounds contain the characteristic C‐glycosidic bond between the open‐chain d‐glucose and the phenol aromatic ring. Therefore, chemical elucidation of the C‐glycosidic bond reactivity is required to exploit their multiple bioactivities. This study developed a method for the divergent synthesis of stachyurin and casuarinin via the α‐selective C‐glycosylation as well as the β‐selective introduction of the oxygen functional group, focusing on structural specificity. The proposed method applies to the syntheses of stachyurin and casuarinin analogues, thereby facilitating the utilisation of their beneficial bioactivities. [ABSTRACT FROM AUTHOR]

Geraniin, an ellagitannin, has shown a potent blood pressure-lowering effect in vivo. Therefore, this study aims to further characterize the ability of geraniin to attenuate hypertensive vascular dysfunction, a key feature of cardiovascular disease (CVD) development. Hypertension was induced in male Sprague-Dawley rats through feeding a high-fat diet (HFD) for eight weeks, followed by oral administration of 25 mg/kg/day geraniin for four weeks. The parameters of vascular dysfunction such as the structure and function of blood vessels as well as the vascular oxidative stress and inflammation were evaluated. The outcomes of geraniin-treated rats were compared with those of untreated rats on either a normal diet (ND) or HFD and with HFD-fed rats treated with captopril (40 mg/kg/day). We found that geraniin supplementation effectively ameliorated HFD-induced hypertension and abnormal remodelling of the thoracic aorta by suppressing excessive vascular superoxide (O2−) radical generation and overexpression of pro-inflammatory mediators in the circulating leukocytes. Furthermore, compared to the ND-fed rats, geraniin also independently promoted the significant enlargement of the thoracic aortic lumen for blood pressure reduction. Notably, the vascular benefits of geraniin were comparable to that of captopril. Collectively, these data suggest that geraniin can mitigate hypertensive vascular remodelling caused by overnutrition, which potentially abrogates the further development of CVDs. [ABSTRACT FROM AUTHOR]

Strictinin is a relatively tiny ellagitannin, which is found in many plants as a minor constituent. Catechins are known as the major constituents in the young leaves of most tea plants, while strictinin was found as a major constituent in the Pu'er tea plant. In some Pu'er tea varieties, strictinin was identified as the most abundant phenolic compound rather than catechins. In the past decade, strictinin was demonstrated to possess several functional activities, including antiviral, antibacterial, anti-obesity, laxative, anticaries, anti-allergic, antipsoriatic, antihyperuricemia, antidiabetic, and anticancer effects. These functional activities were in accordance with the therapeutic effects empirically perceived for Pu'er tea. Evidently, strictinin is the key ingredient in Pu'er tea that acts as a herbal medicine. In functionally-based applications, an instant powder of Pu'er tea infusion was formulated as an active raw material to be supplemented in food, cosmetics, and beverages; a new type of tea named Bitter Citrus Tzen Tea was developed by combining three teas empirically consumed to expel the cold, and new edible oral care products were designed for caries prevention by supplementation with Pu'er tea extract. More functional activities and practical applications of strictinin are scientifically anticipated in follow-up research. [ABSTRACT FROM AUTHOR]

Oligomeric ellagitannins are challenging synthetic targets due to the need for an abundant supply of their composed monomeric ellagitannins and a synthetic methodology to connect them. This work focused on the divergent synthesis of the four monomeric ellagitannins from a common intermediate as a step toward the total synthesis of nobotanin K, a class of compounds that includes oligomeric ellagitannins and were isolated in plants belonging to the Melastomataceae family. Implementing our method, the four natural products could be easily supplied, suggesting that through this novel route, the total synthesis of nobotanin K could be achieved smoothly.

(1) Background: The findings of our recent in vivo study indicated that the oral administration of oenothein B, a unique macrocyclic ellagitannin, activated extracellular signal-regulated kinase (ERK) 2 and cAMP response element-binding protein (CREB) in the mouse brain. A large hydrophilic oenothein B is unable to reach the brain, suggesting that any metabolite(s) of oenothein B might function in the brain. (2) Results: The addition of oenothein B to the culture medium of rat cortical neurons induced the prompt and significant activation of ERK2 and CREB. (3) Conclusions: The activation of ERK2 and CREB is crucial for synaptic transmission and learning/memory formation in the brain. The present results suggest oenothein B exerts neurotrophic/neuroprotective effects in the brain through the modulation of neuronal signaling pathways, if it reaches the brain.

The identification of unstable metabolites of ellagitannins having ortho-quinone structures or reactive carbonyl groups is important to clarify the biosynthesis and degradation of ellagitannins. Our previous studies on the degradation of vescalagin, a major ellagitannin of oak young leaves, suggested that the initial step of the degradation is regioselective oxidation to generate a putative quinone intermediate. However, this intermediate has not been identified yet. In this study, young leaves of Quercus dentata were extracted with 80% acetonitrile containing 1,2-phenylenediamine to trap unstable ortho-quinone metabolites, and subsequent chromatographic separation afforded a phenazine derivative of the elusive quinone intermediate of vescalagin. In addition, phenylenediamine adducts of liquidambin and dehydroascorbic acid were obtained, which is significant because liquidambin is a possible biogenetic precursor of C-glycosidic ellagitannins and ascorbic acid participates in the production of another C-glycosidic ellagitannin in matured oak leaves. [ABSTRACT FROM AUTHOR]

Ellagitannins are a class of plant polyphenols with a structural diversity of around 1000. Because those with attractive biological activities have been reported, synthetic studies have been performed. The purpose of this perspective is to provide an outlook toward future developments on ellagitannin chemistry and medicinal applications by overviewing synthetic studies. In particular, we summarize recent synthetic efforts of ellagitannins via functionalization of the glucose core and stereodivergent construction of the characteristic hydroxydiphenoic groups. The development of chemical probes utilizing natural ellagitannins is also introduced.

Ellagitannin-rich food has been implicated to ameliorate cardiovascular risk, particularly blood pressure (BP). This systematic review and meta-analysis investigated the effect of ellagitannin-rich fruit consumption on BP. Five databases were screened and RCTs reporting the effect of ellagitannin-rich fruit consumption on BP and polyphenol content were included. Nineteen studies with 1,249 participants, showed a non-significant systolic blood pressure (SBP) and significant diastolic blood pressure (DBP) reduction, with ET-rich fruit consumption. Subgroup analysis revealed significant SBP reduction among hypertensives receiving 500–1000 mg polyphenol (-4.95 mmHg, 95 % CI: [-7.24, −2.66]) and among metabolic syndrome (MS) patients (-3.44 mmHg; 95 % CI: [-5.25, −1.63]). meta-regression revealed a positive association between polyphenol dosage and SBP changes. In conclusion, the consumption of ellagitannin-rich fruits may be considered an anti-hypertensive functional food/drink and recommended for patients who are at high risk for hypertension. Further well-designed trials are required to resolve the significant heterogeneities identified in the current literature.

Terminalia chebula, (Family: Combretaceae) is a medicinally active plant possess a wide spectrum of biological activities and contain numerous bioactive phytoconstituents like phenolic compounds, hydrolysable tannins, and flavonoids, therefore it may be considers as a good therapeutic alternative. Chebulinic acid, an ellagitannin was isolated from the fruits of Terminalia chebula and was known to possess numerous biological activities including anti-tumor activity, anti-atherogenic, anti-fibrotic, anti-inflammatory, antiulcer, antioxidant, hepatoprotective, antidiabetic, and antiviral etc. The present chapter describes the various analytical methods, structure elucidation, biological activities, pharmacokinetic, patents and various marketed formulations. Thus, chebulinic acid and related derivatives of Terminalia chebula and other plant species possess numerous pharmacological which paves way for further studies.

Oligomeric ellagitannins are challenging synthetic targets due to the need for an abundant supply of their composed monomeric ellagitannins and a synthetic methodology to connect them. This work focused on the divergent synthesis of the four monomeric ellagitannins from a common intermediate as a step toward the total synthesis of nobotanin K, a class of compounds that includes oligomeric ellagitannins and were isolated in plants belonging to the Melastomataceae family. Implementing our method, the four natural products could be easily supplied, suggesting that through this novel route, the total synthesis of nobotanin K could be achieved smoothly. [ABSTRACT FROM AUTHOR]

The therapeutic effects of food rich in ellagitannins have been established to stem from its microbial metabolite, urolithin. Over the past decade, there has been a growing trend in urolithin research pertaining to its pharmacological properties. The purpose of this systematic review is to collate and synthesise all available data on urolithin's therapeutic ability, to highlight its potential as a pharmaceutical agent, and prospective direction on future research. Methods: This systematic review was written based on the PRISMA guideline and was conducted across Ovid via Embase, Ovid MEDLINE, Cochrane Central Register for Controlled Trials, and Web of Science Core Collection. Results: A total of 41 animal studies were included in this systematic review based on the appropriate keyword. The included studies highlighted the neuroprotective, anti-metabolic disorder activity, nephroprotective, myocardial protective, anti-inflammatory, and musculoskeletal protection of urolithin A, B, and its synthetic analogue methylated urolithin A. The Sirt1, AMPK, and PI3K/AKT/mTOR signalling pathways were reported to be involved in the initiation of autophagy and mitochondrial biogenesis by urolithin A. Conclusions: This review methodically discusses the therapeutic prospects of urolithins and provides scientific justification for the potential development of urolithin A as a potent natural mitophagy inducer for anti-ageing purposes. [ABSTRACT FROM AUTHOR]

Due to their chemical properties and biological activity, antioxidants of plant origin have gained interest as valuable components of the human diet, potential food preservatives and additives, ingredients of cosmetics and factors implicated in tolerance mechanisms against environmental stress. Plant polyphenols are the most prominent and extensively studied, albeit not only group of, secondary plant (specialized) metabolites manifesting antioxidative activity. Because of their potential economic importance, the productive and renewable sources of the compounds are desirable. Over thirty years of research on hairy root cultures, as both producers of secondary plant metabolites and experimental systems to investigate plant biosynthetic pathways, brought about several spectacular achievements. The present review focuses on the Rhizobium rhizogenes-transformed roots that either may be efficient sources of plant-derived antioxidants or were used to elucidate some regulatory mechanisms responsible for the enhanced accumulation of antioxidants in plant tissues. [ABSTRACT FROM AUTHOR]

Having served as a symbolic fruit since ancient times, pomegranate (Punica granatum) has also gained considerable recognition as a functional food in the modern era. A large body of literature has linked pomegranate polyphenols, particularly anthocyanins (ATs) and hydrolyzable tannins (HTs), to the health-promoting activities of pomegranate juice and fruit extracts. However, it remains unclear as to how, and to what extent, the numerous phytochemicals in pomegranate may interact and exert cooperative activities in humans. In this review, we examine the structural and analytical information of the diverse phytochemicals that have been identified in different pomegranate tissues, to establish a knowledge base for characterization of metabolite profiles, discovery of novel phytochemicals, and investigation of phytochemical interactions in pomegranate. We also assess recent findings on the function and molecular mechanism of ATs as well as urolithins, the intestinal microbial derivatives of pomegranate HTs, on human nutrition and health. A better understanding of the structural diversity of pomegranate phytochemicals as well as their bioconversions and bioactivities in humans will facilitate the interrogation of their synergistic/antagonistic interactions and accelerate their applications in dietary-based cancer chemoprevention and treatment in the future.

Background: Punicalagin (PG), a component of Punica granatum L., present a significant nutraceutical value in view of its numerous health-promoting properties and abundance. Interest in PG is driven by its complex structure, as the largest molecular weight ellagitannin. Promising results from the consumption of pomegranate juice in clinical trials against several ailments i.e., cardiovascular diseases, diabetes, and prostate cancer have been mostly attributed to its PG content. In recent years, PG has been demonstrated to exhibit excellent pharmacological bioactivities and has been proposed as a safe candidate for chemoprevention. Purpose: To assess the underlying PG's action mechanisms towards chronic diseases with high mortality and morbidity. Methods: Electronic databases including PubMed, ScienceDirect and Scopus were used to compile the literature. Papers describing the biological effects of punicalagin in vitro conditions, experimental animal models, and humans were selected and discussed. In addition, the extraction and isolation procedure with the highest punicalagin yield was included. Results: Among the 1757 primarily selected papers, only a final number of 119 studies were included. The mechanisms of actions ranged from selective induction of apoptosis of cancer cells, autophagy of cancer cells, decrease in oxidative stress, reduction of inflammation via down-regulation of pro-inflammatory factors and up-regulation of anti-inflammatory mediators to maintaining neuronal integrity. This review presents the latest research progress made towards PG role in the prevention and treatment of various chronic diseases and its protective health effects highlighting the need for future research in nutraceuticals. Despite the promising effects of punicalagin, there seems to be a need for human trials to confirm the effects at physiological levels as there can be substantial human inter-individual variability in response to punicalagin metabolism. Further, comparison of the different extraction and isolation methods are presented to highlight the most optimum for PG recovery. Conclusion: This review aims at improving the value-added applications of this unique dietary bioactive phenolic at a commercial scale in view of its role in health and disease management.

Strictinin is a relatively tiny ellagitannin, which is found in many plants as a minor constituent. Catechins are known as the major constituents in the young leaves of most tea plants, while strictinin was found as a major constituent in the Pu’er tea plant. In some Pu’er tea varieties, strictinin was identified as the most abundant phenolic compound rather than catechins. In the past decade, strictinin was demonstrated to possess several functional activities, including antiviral, antibacterial, anti-obesity, laxative, anticaries, anti-allergic, antipsoriatic, antihyperuricemia, antidiabetic, and anticancer effects. These functional activities were in accordance with the therapeutic effects empirically perceived for Pu’er tea. Evidently, strictinin is the key ingredient in Pu’er tea that acts as a herbal medicine. In functionally-based applications, an instant powder of Pu’er tea infusion was formulated as an active raw material to be supplemented in food, cosmetics, and beverages; a new type of tea named Bitter Citrus Tzen Tea was developed by combining three teas empirically consumed to expel the cold, and new edible oral care products were designed for caries prevention by supplementation with Pu’er tea extract. More functional activities and practical applications of strictinin are scientifically anticipated in follow-up research.

Isothermal titration calorimetry (ITC) was used to study the interactions between hydrolysable tannins (HTs) and lipid vesicles prepared from a phospholipid extract of Escherichia coli (E. coli). A group of 24 structurally different HTs was selected, and structural differences affecting their affinities to interact with lipid vesicles in aqueous buffered media were identified. In general, the interactions between HTs and lipid vesicles were exothermic in nature, and ITC as a technique functioned well in the screening of HTs for their affinity for lipids. Most notably, the galloyl moiety, the structural flexibility of the entire tannin structure, the hydrophobicity of the tannin, and higher molecular weight were observed to be important for the stronger interactions with the lipids. The strongest interactions with lipids were observed for rugosins D and G. It was also observed that some HTs with moderate hydrophobicities, such as geraniin, chebulagic acid, and chebulinic acid, did not have any detectable interactions with the lipid vesicles, suggesting that a hydrophobic structure alone does not guarantee an affinity for lipids. [ABSTRACT FROM AUTHOR]

Background: Excessive ingestion of fructose can lead to obesity and related diseases. Eucalyptus leaf extract (ELE) contains oenothein B, which inhibits intestinal fructose absorption. Objective: The anti-obesity effects of ELE containing oenothein B were evaluated in healthy Japanese individuals whose body mass index (BMI) was ≥ 23 and < 30 kg/m² . Methods: A randomized, placebo-controlled, double-blind, parallel-group study was performed to evaluate the effect of ELE consumption, for 12 weeks at a 3.38 mg/day dose of oenothein B, on the abdominal visceral fat area (VFA) as the primary outcome. The results were compared to those of a placebo group. Results: Of the 721 individuals who underwent screening, 198 were randomly allocated into two groups. A total of 95 subjects in the placebo group and 94 in the intervention group were established as the per-protocol set. VFA in the intervention group significantly decreased compared to that in the placebo group 12 weeks after initiating intervention. This reduction in VFA was considered to have clinical significance. Among the secondary outcomes, VFA, waist circumference, and muscle mass after 8 weeks, as well as body weight and BMI after 12 weeks, were significantly lower in the intervention group compared to the placebo group. Conclusion: ELE containing oenothein B may be effective against obesity and related diseases by reducing VFA levels. [ABSTRACT FROM AUTHOR]

Geraniin, an ellagitannin, has ameliorative properties against high-fat diet (HFD)-induced metabolic syndrome. Since geraniin has poor bioavailability, we hypothesised the interaction of this compound with gut microbiota as the main mechanism for improving metabolic aberrations. Male Sprague Dawley rats were divided into normal diet (ND)- and HFD-fed animals and treated with geraniin and an enriched extract of geraniin (GEE). We observed that 5 mg geraniin and 115 mg GEE supplementation significantly attenuated glucose intolerance, lipopolysaccharide-binding protein, total cholesterol, triacylglyceride, and low-density lipoprotein; improved insulin sensitivity; and significantly increased adiponectin and hepatic PPARα expression. Although geraniin and GEE did not significantly alter the gut microbial composition, we found an increment in the relative abundance of a few butyrate producers such as Alloprevotella, Blautia, Lachnospiraceae NK4A136 group, and Clostridium sensu stricto 1. Geraniin and its enriched extract's ability to ameliorate metabolic syndrome parameters while positively affecting the growth of butyrate-producing bacteria suggests its potential prebiotic role. [ABSTRACT FROM AUTHOR]

Ellagitannins (ETs) are hydrolysable tannins composed of a polyol core, primarily glucose, which is esterified with hexahydroxydiphenic acid (HHDP), and in some cases, gallic acid. ETs are the major phenolic compounds found in strawberries and may contribute to the health-related properties of strawberries, because of their strong antioxidative activity. However, their distribution in the strawberry fruit remains unclear. In this study, matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI–MSI) was used to visualize ETs in ripe strawberry fruits. Five peaks, corresponding to the m/z values of ET [M−H]− ions detected in the MALDI–MS spectrum of strawberry extracts, were identified as strictinin, pedunculagin, casuarictin, davuriicin M1, and an unknown ET using MALDI–tandem MS (MS/MS). In addition, liquid chromatography–electrospray ionization–MS/MS of the extracts revealed the presence of pedunculagin isomers and the unknown ET. Ion images of these five ETs were reconstructed using MALDI–MSI. Strictinin was widely distributed in and around the achene seed coats, while the other ETs were dispersed in and around the seed coats, and at the bottom of the receptacle; pedunculagin was distributed in the epidermis and pith, whereas casuarictin, the unknown ET, and davuriicin M1 were distributed in the pith. Moreover, MALDI–MSI of a casuarictin standard indicated that in-source fragmentation weakly affected the ion images. The results suggest that the distribution of ETs depends on the presence or absence of their constituents, namely galloyl units, HHDP, and bis-HHDP. To the best of my knowledge, this is the first report on the visualization of ETs in plant tissues using MSI, MALDI–MSI may be a useful tool for analyzing the distribution of ETs in the strawberry fruit.

Abstract The search for safe and effective ferroptosis‐inhibitors has become an important topic. Geraniin, an ellagitannin bearing hexahydroxydiphenoyl (HHDP) and dehydrohexahydroxydiphenoyl (DHHDP) groups, was observed to inhibit erastin‐induced ferroptosis in bone marrow‐derived mesenchymal stem cells (bmMSCs). To determine the mechanism, geraniin was further analyzed using UV‐vis spectra and several colorimetric assays, where its IC50 values were always much lower than that of the Trolox positive control. When interacted with several free radicals, geraniin gave no radical adduct formation (RAF) peak in the ultra‐performance liquid chromatography coupled with electrospray ionization quadrupole time‐of‐flight tandem mass spectrometry. In conclusion, geraniin exhibits ferroptosis‐inhibitory potential towards erastin‐treated bmMSCs; such potential may mainly stem from its strong lipid peroxidation (LPO)‐inhibition, Fe2+‐chelating, and antioxidant actions. Geraniin gives neither dimer nor radical adduct, owing to the bulky HHDP (or DHHDP) group; thus, it is considered as a safe and effective ferroptosis‐inhibitor.

Obesity is a global health concern associated with the dysbiosis of intestinal microbial composition. In this study, we investigated the potentials of urolithin A (Uro-A) and urolithin B (Uro-B), two gut microbiota-derived metabolites of ellagitannins, in reducing body weight gain through the modulation of the gut microbiota. We established a high-fat diet (HFD)-induced obesity model in rats that were later administered with either 2.5 mg/kg of Uro-A or Uro-B. Serum biochemical parameters were quantified, and changes in the composition of the gut microbial community were analysed using 16S rDNA gene sequencing. Our results showed that the urolithins significantly decreased the body weight in HFD-fed rats and restored serum lipid profile. The taxonomic analysis showed that both Uro-A and Uro-modulated gut microbes related to body weight, dysfunctional lipid metabolism and inflammation. Overall, our results suggest that Uro-A and Uro-B possess anti-obesity properties, which may be related to the modulation of the gut microbial composition. [ABSTRACT FROM AUTHOR]

Total synthesis of nilotinin M3, which is a member of the ellagitannin family of natural products containing an isodehydrodigalloyl (isoDHDG) group, was achieved using the Ullmann reaction to construct a highly functionalized diaryl ether. [ABSTRACT FROM AUTHOR]

This study describes the total synthesis of macaranin B, a naturally occurring ellagitannin containing 1- O -galloyl and 3,6- O -macaranoyl groups in an axial-rich d -glucose. The key steps of the synthesis include an oxidative coupling reaction of galloyl groups with 1,2,4-orthoacetylglucose moiety and oxa -Michael addition/elimination using an orthoquinone monoketal. This facilitates the construction of the macaranoyl group and the first total synthesis of macaranin B. [ABSTRACT FROM AUTHOR]

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Our examination of high molecular weight polyphenolic constituents in the leaves of Barringtonia racemosa of the family Lecythidaceae uncovered 5 previously undescribed ellagitannins. One, barringtin M1 (1), among them was a hydrolysable tannin monomer, while remaining 4, barringtins D1 (2), D2 (3), D3 (4), and barricyclin D1 (5), were all dimers. Barricyclin D1 had a first macrocyclic structure formed from casuarictin (6) and tellimagrandin I (7), and the other ellagitannins had structures related to 5. Two additional known phenolics, valoneic acid dilactone (8) and schimawalin A (9), were also isolated from the leaves. These results suggested that the leaves of B. racemosa are a natural resource rich in hydrolysable tannin oligomers. [ABSTRACT FROM AUTHOR]

Due to their chemical properties and biological activity, antioxidants of plant origin have gained interest as valuable components of the human diet, potential food preservatives and additives, ingredients of cosmetics and factors implicated in tolerance mechanisms against environmental stress. Plant polyphenols are the most prominent and extensively studied, albeit not only group of, secondary plant (specialized) metabolites manifesting antioxidative activity. Because of their potential economic importance, the productive and renewable sources of the compounds are desirable. Over thirty years of research on hairy root cultures, as both producers of secondary plant metabolites and experimental systems to investigate plant biosynthetic pathways, brought about several spectacular achievements. The present review focuses on the Rhizobium rhizogenes-transformed roots that either may be efficient sources of plant-derived antioxidants or were used to elucidate some regulatory mechanisms responsible for the enhanced accumulation of antioxidants in plant tissues.

Isothermal titration calorimetry (ITC) was used to study the interactions between hydrolysable tannins (HTs) and lipid vesicles prepared from a phospholipid extract of Escherichia coli (E. coli). A group of 24 structurally different HTs was selected, and structural differences affecting their affinities to interact with lipid vesicles in aqueous buffered media were identified. In general, the interactions between HTs and lipid vesicles were exothermic in nature, and ITC as a technique functioned well in the screening of HTs for their affinity for lipids. Most notably, the galloyl moiety, the structural flexibility of the entire tannin structure, the hydrophobicity of the tannin, and higher molecular weight were observed to be important for the stronger interactions with the lipids. The strongest interactions with lipids were observed for rugosins D and G. It was also observed that some HTs with moderate hydrophobicities, such as geraniin, chebulagic acid, and chebulinic acid, did not have any detectable interactions with the lipid vesicles, suggesting that a hydrophobic structure alone does not guarantee an affinity for lipids.

This study compared the efficacy of aqueous extracts of commercially available pomegranate peel products and a juice powder in inhibiting the growth of two enterohemorrhagic Escherichia coli strains. Cell suspension of each E. coli strain (5 Log CFU/ml) was added into tryptic soy broth amended with 9 or 23% of each extract prepared with two different methods. After treatment for 5, 10, and 24 h at 25 °C, surviving E. coli cells were enumerated on tryptic soy agar to determine cell population reduction compared to the controls. The concentrations of six different ellagitannins and titratable activity in each treatment system were determined and correlated to E. coli cell population reduction. The extracts from three powdered pomegranate peels caused a significantly greater ( p  ≤ 0.05) reduction in E. coli population than the extract from the whole peel and juice powder. The higher dose of extracts resulted in a greater cell population reduction than the lower dose. The level of E. coli population reduction correlated positively with the total ellagitannins content (R 2 0.67-0.98) and the titratable acidity (R 2 0.69-0.98) in the treatment systems. The study suggests that pomegranate peels are promising natural additives or preservatives to control pathogens like EHEC., Competing Interests: All authors have participated in (a) conception and design, or analysis and interpretation of the data; (b) drafting the article or revising it critically for important intellectual content; and (c) approval of the final version. This manuscript has not been submitted to, nor is under review at, another journal or other publishing venue. The authors have no affiliation with any organization with a direct or indirect financial interest in the subject matter discussed in the manuscript The following authors have affiliations with organizations with direct or indirect financial interest in the subject matter discussed in the manuscript., (© 2024 The Authors.)

Geraniin, an ellagitannin, has ameliorative properties against high-fat diet (HFD)-induced metabolic syndrome. Since geraniin has poor bioavailability, we hypothesised the interaction of this compound with gut microbiota as the main mechanism for improving metabolic aberrations. Male Sprague Dawley rats were divided into normal diet (ND)- and HFD-fed animals and treated with geraniin and an enriched extract of geraniin (GEE). We observed that 5 mg geraniin and 115 mg GEE supplementation significantly attenuated glucose intolerance, lipopolysaccharide-binding protein, total cholesterol, triacylglyceride, and low-density lipoprotein; improved insulin sensitivity; and significantly increased adiponectin and hepatic PPARα expression. Although geraniin and GEE did not significantly alter the gut microbial composition, we found an increment in the relative abundance of a few butyrate producers such as Alloprevotella, Blautia, Lachnospiraceae NK4A136 group, and Clostridium sensu stricto 1. Geraniin and its enriched extract’s ability to ameliorate metabolic syndrome parameters while positively affecting the growth of butyrate-producing bacteria suggests its potential prebiotic role.

There is a significant need to gain access to new and better antibacterial agents. Acalypha arvensis, a plant from the Euphorbiaceae family, has been used in traditional medicine for centuries to treat infectious diseases. This manuscript reports the isolation, characterization, and antibacterial screening of 8 natural products extracted from maceration of aerial parts of Acalypha arvensis. Specifically, three extracts were assessed (n-hexane, ethyl acetate, and ethanol), in which antibacterial activity was evaluated against diverse bacterial strains. The ethanolic extract showed the best activity against methicillin-sensitive and methicillin-resistant Staphylococcus aureus, Klebsiella pneumoniae, and Pseudomonas aeruginosa strains, which supports the medicinal properties attributed to this plant. The chromatographic fractions AaR4 and AaR5 were the most bioactive, in which the ellagitannin natural product known as corilagin (1) was identified for the first time in this plant. Therefore, it can be said that this is the main chemical responsible for the observed antibacterial activity. However, we also identified chlorogenic acid (2), rutin (3), quercetin-3-O-glucoside (4), caffeic acid (5), among others (6–8). Hence, this plant can be considered to be a good alternative to treat health-related issues caused by various bacteria.

BACKGROUND: Purple Queen® is an early ripening pomegranate cultivar growing well in soilless cultivation. Substrates have direct effects on plant development and, due to progressive peatland exhaustion, the request for new materials for plant growth is high. OBJECTIVE: The objective of this work was to verify the effects of a new potential substrate obtained from the remediation of marine port sediments on the nutraceutical profile of Purple Queen® fruits, using 50% and 100% of reclaimed sediment. METHODS: The study was carried out determining ellagitannins and polysaccharides obtained from peel after decoction, and anthocyanins in aril juice on fruits from two agronomic seasons. RESULTS: The presence of 100% of the sediment had a partial detrimental effect on fruits size and weight. Compared to a peat-based commercial substrate (control), remediated sediment preserved ellagitannin content and increased the anthocyanin amount (up to 40% higher) and polysaccharide content up to 34% on dry fruit. High molecular weight polysaccharides (>2000 kDa) were identified in all the fruits with glucose and galacturonic acid as the major sugars. CONCLUSIONS: Fruits from plants cultivated only on sediment or in a mixture with 50% of peat showed significant increases of bioactive compounds as stress response in two consecutive seasons. [ABSTRACT FROM AUTHOR]

Serratia liquefaciens is a spoilage microorganism of relevance in the dairy industry because it is psychrotrophic, able to form biofilm, and produces thermoresistant proteases and lipases. Phenolic compounds and furanones have been studied as inhibitors of biofilm formation. In this study, the potential of the pulp phenolic extract of Eugenia uniflora L. orange fruits, also called pitanga, and furanone C30 on the inhibition of biofilm formation by S. liquefaciens L53 and the susceptibility to different antimicrobials were evaluated. The pulp phenolic extract of pitanga had a high total phenolic content, being mainly composed of glycosylated quercetins and ellagitannins. Sub-inhibitory concentrations of this extract and furanone reduced biofilm formation by S. liquefaciens on polystyrene and the amount of polysaccharides, proteins and extracellular DNA in the biofilms. These biofilms were also more susceptible to kanamycin. The combinations of furanone with phenolic extract of pitanga or kanamycin showed a synergistic effect with total growth inhibition of S. liquefaciens. [ABSTRACT FROM AUTHOR]

Summary: The aim of this study was to investigate the inhibitory mechanism of oenothein B (OeB), a unique oligomer ellagitannin with a rigid structure, on porcine trypsin using fluorescence spectroscopy, isothermal titration calorimetry (ITC), circular dichroism (CD) and molecular docking. Trypsin activity was strongly inhibited by OeB in a competitive way. Fluorescence quenching of trypsin by OeB was a static quenching. The CD spectra showed that binding of OeB to trypsin altered trypsin's conformation. The ITC and docking studies revealed that the inhibitory mechanism of OeB occurred via binding to the interior hydrophobic groups of trypsin and the formation of hydrogen bonds with trypsin through binding to the amino acid residues Asn97, His573, Ser195 and Gln192. This study provides a theoretical and computational basis for the precise control of trypsin in food industry. Based on the results, OeB may be used in food technology research as novel bioactive trypsin inhibitor. [ABSTRACT FROM AUTHOR]

This work aimed to characterize the phenolic composition and in vitro antioxidant and antiproliferative properties of lyophilized camu-camu (Myrciaria dubia) seed extract (LCE), and to assess the effects of LCE on the antioxidant and sensory traits of yogurt. The LCE contained 46.3% (wt/wt) total phenolic content; the main compounds quantified were vescalagin, castalagin, gallic acid, procyanidin A2, and (−)-epicatechin. The LCE had antioxidant activity, as measured by different chemical assays (2,2-diphenyl-1-picrylhydrazyl, Folin–Ciocalteu reducing capacity, total reducing capacity, ferric reducing antioxidant power, and Cu2+ chelating capacity), and inhibited the cell proliferation of HepG2 cells (human hepatoma carcinoma; IC50 = 1,116 µg/mL) and Caco-2 cells (human colorectal adenocarcinoma epithelial cells; IC50 = 608.5 µg/mL). In addition, LCE inhibited the in vitro activity of α-amylase, α-glucosidase, and angiotensin-converting enzyme, and protected DNA from peroxyl radical–induced scission. When added to yogurts, different concentrations of LCE (0, 0.25, 0.5, 0.75, and 1.0 g/100 g) increased the chemical antioxidant and reducing capacities. The camu-camu yogurt containing LCE at 0.25 g/100 g had an acceptance index of 84%, showing that camu-camu seed extract may be a potential ingredient for addition to yogurts. [ABSTRACT FROM AUTHOR]

The blackberry seed flour was cold‐extracted using 50% acetone and examined for its phytochemical composition and health‐beneficial properties including in vitro gut microbiota modulatory, free radical scavenging, anti‐inflammatory, and antiproliferative capacities. Among identified thirteen components of blackberry seed flour extract through UHPLC‐MS analysis, sanguiin H6 was the primary component and followed by ellagic acid and pedunculagin. For health‐beneficial properties, the blackberry seed flour extract increased the total number of gut bacteria and shifted the abundance of specific bacterial phylum, family, or genus. The extract had RDSC, ORAC, HOSC, and ABTS•+ scavenging capacities of 362, 304, 2,531, and 267 μmol Trolox equivalents (TE)/g, respectively. In addition, the blackberry seed flour extract showed capacities for anti‐inflammation and antiproliferation by suppressing LPS induced IL‐1β mRNA expressions in the cultured J774A.1 mouse macrophages and the proliferation of LNCaP prostate cancer cells. The results suggest potential health benefits and further utilization of blackberry seed flour as functional foods. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus is the most common cause of surgical site infections and its treatment is challenging due to the emergence of multi-drug resistant strains such as methicillin-resistant S. aureus (MRSA). Natural berry-derived compounds have shown antimicrobial potential, e.g., ellagitannins such as sanguiin H-6 and lambertianin C, the main phenolic compounds in Rubus seeds, have shown antimicrobial activity. The aim of this study was to evaluate the effect of sanguiin H-6 and lambertianin C fractionated from cloudberry seeds, on the MRSA growth, and as treatment of a MRSA biofilm development in different growth media in vitro and in vivo by using a murine wound infection model where sanguiin H-6 and lambertianin C were used to prevent the MRSA infection. Sanguiin H-6 and lambertianin C inhibited the in vitro biofilm development and growth of MRSA. Furthermore, sanguiin H-6 showed significant anti-MRSA effect in the in vivo wound model. Our study shows the possible use of sanguiin H-6 as a preventive measure in surgical sites to avoid postoperative infections, whilst lambertianin C showed no anti-MRSA activity.

Inhibition of fructose absorption may suppress adiposity and adiposity-related diseases caused by fructose ingestion. Eucalyptus leaf extract (ELE) inhibits intestinal fructose absorption (but not glucose absorption); however, its active compound has not yet been identified. Therefore, we evaluated the inhibitory activity of ELE obtained from Eucalyptus globulus using an intestinal fructose permeation assay with the human intestinal epithelial cell line Caco-2. The luminal sides of a cell monolayer model cultured on membrane filters were exposed to fructose with or without the ELE. Cellular fructose permeation was evaluated by measuring the fructose concentration in the medium on the basolateral side. ELE inhibited 65% of fructose absorption at a final concentration of 1 mg/mL. Oenothein B isolated from the ELE strongly inhibited fructose absorption; the inhibition rate was 63% at a final concentration of 5 μg/mL. Oenothein B did not affect glucose absorption. In contrast, the other major constituents (i.e., gallic acid and ellagic acid) showed little fructose-inhibitory activity. To our knowledge, this is the first report that oenothein B in ELE strongly inhibits fructose absorption in vitro. ELE containing oenothein B can prevent and ameliorate obesity and other diseases caused by dietary fructose consumption.

In this study, we present the isolation and characterization of the structure of six gallotannins (1–6), three ellagitannins (7–9), a neolignan glucoside (10), and three related polyphenolic compounds (gallic acid, 11 and 12) from Trapa bispinosa Roxb. pericarp extract (TBE). Among the isolates, the structure of compound 10 possessing a previously unclear absolute configuration was unambiguously determined through nuclear magnetic resonance and circular dichroism analyses. The α-glucosidase activity and glycation inhibitory effects of the isolates were evaluated. Decarboxylated rugosin A (8) showed an α-glucosidase inhibitory activity, while hydrolyzable tannins revealed stronger antiglycation activity than that of the positive control. Furthermore, the identification and quantification of the TBE polyphenols were investigated by high-performance liquid chromatography coupled to ultraviolet detection and electrospray ionization mass spectrometry analysis, indicating the predominance of gallic acid, ellagic acid, and galloyl glucoses showing marked antiglycation properties. These findings suggest that there is a potential food industry application of polyphenols in TBE as a functional food with antidiabetic and antiglycation activities.

The search for safe and effective ferroptosis‐inhibitors has become an important topic. Geraniin, an ellagitannin bearing hexahydroxydiphenoyl (HHDP) and dehydrohexahydroxydiphenoyl (DHHDP) groups, was observed to inhibit erastin‐induced ferroptosis in bone marrow‐derived mesenchymal stem cells (bmMSCs). To determine the mechanism, geraniin was further analyzed using UV‐vis spectra and several colorimetric assays, where its IC50 values were always much lower than that of the Trolox positive control. When interacted with several free radicals, geraniin gave no radical adduct formation (RAF) peak in the ultra‐performance liquid chromatography coupled with electrospray ionization quadrupole time‐of‐flight tandem mass spectrometry. In conclusion, geraniin exhibits ferroptosis‐inhibitory potential towards erastin‐treated bmMSCs; such potential may mainly stem from its strong lipid peroxidation (LPO)‐inhibition, Fe2+‐chelating, and antioxidant actions. Geraniin gives neither dimer nor radical adduct, owing to the bulky HHDP (or DHHDP) group; thus, it is considered as a safe and effective ferroptosis‐inhibitor. [ABSTRACT FROM AUTHOR]

Despite the lack of its toxicity evaluation, traditional herbal products are being widely used for various health indications. Geraniin, an ellagitannin, is a bioactive compound found in many traditional herbal medicines. In spite its numerous health benefits ranging from anti-inflammatory, anti-hyperglycaemic, hepatoprotective, anti-cancer and anti-microbial, no toxicity data on geraniin is available. The objective of this study is to evaluate the acute oral toxicity of geraniin and an enriched geraniin-extract of Nephelium lappaceum L rind. This study followed the guidelines of the OECD 423 acute oral toxicity test. Subsequent to a single oral administration of the test compounds, the rats were observed for 14 days for signs of toxicity and mortality. Following euthanasia, full blood count, biochemistry of blood and histopathology assessment of organs were carried out. All parameters analysed indicated insignificant difference compared to control. The LD50 cut-off values for both geraniin and geraniin-enriched extract was established to be 2000 mg/kg b. w., following a single oral dose. It was however observed that the hepatocytes of three geraniin-administered rats exhibited a ‘foamy appearance’. As such, the no-observed-adverse-effect level of geraniin is below 2000 mg/kg, while that of geraniin-enriched extract is up to 2000 mg/kg. Further detailed toxicity studies are required to establish geraniin or its enriched extract from Nephelium lappaceum L rind safe for human consumption.

Tannins are a group of polyphenols that possess the ability to precipitate proteins, causing an undesirable astringent taste by interacting with salivary peptides. This interaction deactivates the digestive enzymes; therefore, tannins are considered as plant defense substances. The health benefits of tannins and related polyphenols in foods and beverages have been demonstrated by biological and epidemiological studies; however, their metabolism in living plants and the chemical changes observed during processing of foods and medicinal herbs raises some questions. This review summarizes our studies concerning dynamic changes observed in tannins. Ellagitannins present in the young leaves of Camellia japonica and Quercus glauca undergo oxidative degradation as the leaves mature. Similar oxidative degradation is also observed in whiskey when it is kept for aging in oak barrels, and in decaying wood caused by fungi in natural forests. In contrast, ellagitannins have been observed to undergo reduction in the leaves of Carpinus, Castanopsis, and Triadica species as the leaves mature. This phenomenon of reductive metabolism in leaves enabled us to propose a new biosynthetic pathway for the most fundamental ellagitannin acyl groups, which was also supported by biomimetic synthetic studies. Polyphenols undergo dynamic changes during the process of food processing. Catechin in tea leaves undergo oxidation upon mechanical crushing to generate black tea polyphenols. Though detailed production mechanisms of catechin dimers have been elucidated, structures of thearubigins (TRs), which are complex mixtures of oligomers, remain ambiguous. Our recent studies suggested that catechin B-ring quinones couple with catechin A-rings during the process of oligomerization.