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Nutrients Nov 2019Punicalagin, a hydrolysable tannin of pomegranate juice, exhibits multiple biological effects, including inhibiting production of pro-inflammatory cytokines in...
Punicalagin, a hydrolysable tannin of pomegranate juice, exhibits multiple biological effects, including inhibiting production of pro-inflammatory cytokines in macrophages. Autophagy, an intracellular self-digestion process, has been recently shown to regulate inflammatory responses. In this study, we investigated the anti-inflammatory potential of punicalagin in lipopolysaccharide (LPS) induced RAW264.7 macrophages and uncovered the underlying mechanisms. Punicalagin significantly attenuated, in a concentration-dependent manner, LPS-induced release of NO and decreased pro-inflammatory cytokines TNF-α and IL-6 release at the highest concentration. We found that punicalagin inhibited NF-κB and MAPK activation in LPS-induced RAW264.7 macrophages. Western blot analysis revealed that punicalagin pre-treatment enhanced LC3II, p62 expression, and decreased Beclin1 expression in LPS-induced macrophages. MDC assays were used to determine the autophagic process and the results worked in concert with Western blot analysis. In addition, our observations indicated that LPS-induced releases of NO, TNF-α, and IL-6 were attenuated by treatment with autophagy inhibitor chloroquine, suggesting that autophagy inhibition participated in anti-inflammatory effect. We also found that punicalagin downregulated FoxO3a expression, resulting in autophagy inhibition. Overall these results suggested that punicalagin played an important role in the attenuation of LPS-induced inflammatory responses in RAW264.7 macrophages and that the mechanisms involved downregulation of the FoxO3a/autophagy signaling pathway.
Topics: Animals; Anti-Inflammatory Agents; Autophagy; Forkhead Box Protein O3; Hydrolyzable Tannins; Inflammation; Lipopolysaccharides; Macrophages; Mice; RAW 264.7 Cells; Signal Transduction
PubMed: 31731808
DOI: 10.3390/nu11112794 -
Oxidative Medicine and Cellular... 2022Ellagic acid (EA) is a bioactive polyphenolic compound naturally occurring as secondary metabolite in many plant taxa. EA content is considerable in pomegranate ( L.)... (Review)
Review
Ellagic acid (EA) is a bioactive polyphenolic compound naturally occurring as secondary metabolite in many plant taxa. EA content is considerable in pomegranate ( L.) and in wood and bark of some tree species. Structurally, EA is a dilactone of hexahydroxydiphenic acid (HHDP), a dimeric gallic acid derivative, produced mainly by hydrolysis of ellagitannins, a widely distributed group of secondary metabolites. EA is attracting attention due to its antioxidant, anti-inflammatory, antimutagenic, and antiproliferative properties. EA displayed pharmacological effects in various and model systems. Furthermore, EA has also been well documented for its antiallergic, antiatherosclerotic, cardioprotective, hepatoprotective, nephroprotective, and neuroprotective properties. This review reports on the health-promoting effects of EA, along with possible mechanisms of its action in maintaining the health status, by summarizing the literature related to the therapeutic potential of this polyphenolic in the treatment of several human diseases.
Topics: Animals; Anti-Allergic Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Ellagic Acid; Fruit; Gastrointestinal Tract; Humans; Hydrolyzable Tannins; Hypoglycemic Agents; Phytotherapy; Plant Extracts; Plants; Polyphenols; Protective Agents
PubMed: 35237379
DOI: 10.1155/2022/3848084 -
Molecular Nutrition & Food Research Nov 2022Urolithins, metabolites produced by the gut microbiota from the polyphenols ellagitannins and ellagic acid, are discovered by the research group in humans almost 20... (Review)
Review
Urolithins, metabolites produced by the gut microbiota from the polyphenols ellagitannins and ellagic acid, are discovered by the research group in humans almost 20 years ago. Pioneering research suggests urolithins as pleiotropic bioactive contributors to explain the health benefits after consuming ellagitannin-rich sources (pomegranates, walnuts, strawberries, etc.). Here, this study comprehensively updates the knowledge on urolithins, emphasizing the review of the literature published during the last 5 years. To date, 13 urolithins and their corresponding conjugated metabolites (glucuronides, sulfates, etc.) have been described and, depending on the urolithin, detected in different human fluids and tissues (urine, blood, feces, breastmilk, prostate, colon, and breast tissues). There has been a substantial advance in the research on microorganisms involved in urolithin production, along with the compositional and functional characterization of the gut microbiota associated with urolithins metabolism that gives rise to the so-called urolithin metabotypes (UM-A, UM-B, and UM-0), relevant in human health. The design of in vitro studies using physiologically relevant assay conditions (molecular forms and concentrations) is still a pending subject, making some reported urolithin activities questionable. In contrast, remarkable progress has been made in the research on the safety, bioactivity, and associated mechanisms of urolithin A, including the first human interventions.
Topics: Male; Humans; Gastrointestinal Microbiome; Coumarins; Hydrolyzable Tannins; Feces; Ellagic Acid; Juglans
PubMed: 35118817
DOI: 10.1002/mnfr.202101019 -
Cell Communication and Signaling : CCS Jan 2019Acetaminophen (APAP) overdose-induced acute liver failure (ALF) is mainly resulted from uncontrolled oxidative stress. Nuclear factor-erythroid 2-related factor 2...
BACKGROUND
Acetaminophen (APAP) overdose-induced acute liver failure (ALF) is mainly resulted from uncontrolled oxidative stress. Nuclear factor-erythroid 2-related factor 2 (Nrf2), a key antioxidant transcription factor, is essential for alleviating APAP-induced hepatotoxicity. Corilagin (Cori) is a natural polyphenol compound that possesses effective antioxidant activity; however, the protective effect of Cori on APAP-induced hepatotoxicity is still unknown. The current study aimed to explore whether Cori could mitigate hepatotoxicity caused by APAP and the underlying molecular mechanisms of action.
METHODS
Cell counting kit-8 (CCK-8) assays, Western blotting analysis, dual-luciferase reporter assays, a mouse model, CRISPR/Cas9 knockout technology, and hematoxylin-eosin (H & E) staining were employed to explore the mechanisms by which Cori exerts a protective effect on hepatotoxicity in HepG2 cells and in a mouse model.
RESULTS
Our findings suggested that Cori efficiently decreased APAP-triggered the generation of reactive oxygen species (ROS) and cell death in HepG2 cells. Additionally, Cori significantly induced the expression of several antioxidant enzymes, and this induced expression was closely linked to the upregulation of Nrf2, inhibition of Keap1 protein expression, and promotion of antioxidant response element (ARE) activity in HepG2 cells. Moreover, Cori clearly induced the phosphorylation of AMP-activated protein kinase (AMPK), glycogen synthase kinase-3β (GSK3β), liver kinase B1 (LKB1) and acetyl-CoA carboxylase (ACC). Furthermore, Cori-mediated GSK3β inactivation, Nrf2 upregulation and cytoprotection were abolished by an AMPK inhibitor (Compound C) in HepG2 cells. Lastly, we found that Cori inhibited APAP-induced hepatotoxicity and mediated the expression of many antioxidant enzymes; these results were reversed in Nrf2 HepG2 cells. In vivo, Cori significantly protected against APAP-induced ALF by reducing mortality and alanine transaminase (ALT) and aspartate aminotransferase (AST) levels, attenuating histopathological liver changes, inhibiting myeloperoxidase (MPO) and malondialdehyde (MDA) levels, and increasing the superoxide dismutase (SOD) content and GSH-to-GSSG ratio as well as suppressing c-jun N-terminal kinase (JNK) phosphorylation. However, Cori-induced reductions in mortality, AST and ALT levels, and histopathological liver changes induced by APAP were clearly abrogated in Nrf2-deficienct mice.
CONCLUSIONS
These findings principally indicated that Cori effectively protects against APAP-induced ALF via the upregulation of the AMPK/GSK3β-Nrf2 signaling pathway.
Topics: AMP-Activated Protein Kinases; Acetaminophen; Animals; Antioxidant Response Elements; Cell Death; Gene Expression Regulation, Neoplastic; Glucosides; Glycogen Synthase Kinase 3 beta; Hep G2 Cells; Humans; Hydrolyzable Tannins; Liver; Liver Failure, Acute; Male; Mice, Inbred C57BL; Models, Biological; NF-E2-Related Factor 2; Oxidative Stress; Protective Agents; Reactive Oxygen Species; Signal Transduction; Up-Regulation
PubMed: 30630510
DOI: 10.1186/s12964-018-0314-2 -
Oxidative Medicine and Cellular... 2022Corilagin, a gallotannin, shows excellent antioxidant and anti-inflammatory effects. The NLRP3 inflammasome dysfunction has been implicated in a variety of inflammation...
Corilagin, a gallotannin, shows excellent antioxidant and anti-inflammatory effects. The NLRP3 inflammasome dysfunction has been implicated in a variety of inflammation diseases. However, it remains unclear how corilagin regulates the NLRP3 inflammasome to relieve gouty arthritis. In this study, bone marrow-derived macrophages (BMDMs) were pretreated with lipopolysaccharide (LPS) and then incubated with NLRP3 inflammasome agonists, such as adenine nucleoside triphosphate (ATP), nigericin, and monosodium urate (MSU) crystals. The MSU crystals were intra-articular injected to induce acute gouty arthritis. Here we showed that corilagin reduced lactate dehydrogenase (LDH) secretion and the proportion of propidium iodide- (PI-)stained cells. Corilagin suppressed the expression of N-terminal of the pyroptosis executive protein gasdermin D (GSDMD-NT). Corilagin restricted caspase-1 p20 and interleukin (IL)-1 release. Meanwhile, corilagin attenuated ASC oligomerization and speck formation. Our findings confirmed that corilagin diminished NLRP3 inflammasome activation and macrophage pyroptosis. We further discovered that corilagin limited the mitochondrial reactive oxygen species (ROS) production and prevented the interaction between TXNIP and NLRP3, but ROS activator imiquimod could antagonize the inhibitory function of corilagin on NLRP3 inflammasome and macrophage pyroptosis. Additionally, corilagin ameliorated MSU crystals induced joint swelling, inhibited IL-1 production, and abated macrophage and neutrophil migration into the joint capsule. Collectively, these results demonstrated that corilagin suppressed the ROS/TXNIP/NLRP3 pathway to repress inflammasome activation and pyroptosis and suggest its potential antioxidative role in alleviating NLRP3-dependent gouty arthritis.
Topics: Humans; Pyroptosis; Inflammasomes; NLR Family, Pyrin Domain-Containing 3 Protein; Reactive Oxygen Species; Hydrolyzable Tannins; Lipopolysaccharides; Arthritis, Gouty; Uric Acid; Antioxidants; Nigericin; Imiquimod; Propidium; Nucleosides; Caspase 1; Inflammation; Interleukin-1beta; Anti-Inflammatory Agents; Adenosine Triphosphate; Adenine; Lactate Dehydrogenases
PubMed: 36299604
DOI: 10.1155/2022/1652244 -
Drug Discoveries & Therapeutics Jul 2022There are trillions of microorganisms in the human intestine. They can react to the intestinal microenvironment by metabolizing food or producing small molecular... (Review)
Review
There are trillions of microorganisms in the human intestine. They can react to the intestinal microenvironment by metabolizing food or producing small molecular compounds to affect the host's digestive ability and resist the risk of infection and autoimmune diseases. Many studies have revealed that intestinal flora and its metabolites play an important role in human physiology and the development of diseases. Urolithins are kind of intestinal microbiota metabolites of ellagitannins (ETs) and ellagic acid (EA) with potent biological activity in vivo. However, different individuals have different intestinal flora. According to the different metabolites from ETs and EA, it is divided into three metabo-types including UM-A, UM-B and UM-0. This paper reviews the origin of urolithins, the urolithin producing microorganisms and the effects of urolithins on regulating intestinal diseases. This review will provide a theoretical basis for the regulation of urolithins in the homeostasis of intestinal flora and a reference for the scientific utilization of urolithins and foods rich in ETs and EA.
Topics: Coumarins; Ellagic Acid; Gastrointestinal Microbiome; Humans; Hydrolyzable Tannins; Intestines
PubMed: 35753772
DOI: 10.5582/ddt.2022.01039 -
Molecules (Basel, Switzerland) Nov 2022Tannins are polyphenols characterized by different molecular weights that plants are able to synthetize during their secondary metabolism. Macromolecules (proteins,... (Review)
Review
Tannins are polyphenols characterized by different molecular weights that plants are able to synthetize during their secondary metabolism. Macromolecules (proteins, structural carbohydrates and starch) can link tannins and their digestion can decrease. Tannins can be classified into two groups: hydrolysable tannins and condensed tannins. Tannins are polyphenols, which can directly or indirectly affect intake and digestion. Their ability to bind molecules and form complexes depends on the structure of polyphenols and on the macromolecule involved. Tannins have long been known to be an "anti-nutritional agent" in monogastric and poultry animals. Using good tannins' proper application protocols helped the researchers observe positive effects on the intestinal microbial ecosystem, gut health, and animal production. Plant tannins are used as an alternative to in-feed antibiotics, and many factors have been described by researchers which contribute to the variability in their efficiencies. The objective of this study was to review the literature about tannins, their effects and use in ruminant nutrition.
Topics: Animals; Tannins; Ecosystem; Ruminants; Polyphenols; Hydrolyzable Tannins; Plants; Animal Feed
PubMed: 36500366
DOI: 10.3390/molecules27238273 -
Nutrients Jun 2021The aim of this publication is to compile a summary of the findings regarding punicalagin in various tissues described thus far in the literature, with an emphasis on... (Review)
Review
The aim of this publication is to compile a summary of the findings regarding punicalagin in various tissues described thus far in the literature, with an emphasis on the effect of this substance on immune reactions. Punicalagin (PUN) is an ellagitannin found in the peel of pomegranate (). It is a polyphenol with proven antioxidant, hepatoprotective, anti-atherosclerotic and chemopreventive activities, antiproliferative activity against tumor cells; it inhibits inflammatory pathways and the action of toxic substances, and is highly tolerated. This work describes the source, metabolism, functions and effects of punicalagin, its derivatives and metabolites. Furthermore, its anti-inflammatory and antioxidant effects are described.
Topics: Animals; Anti-Inflammatory Agents; Biological Availability; Ellagic Acid; Humans; Hydrolyzable Tannins; Immunosuppressive Agents; Metabolome
PubMed: 34201484
DOI: 10.3390/nu13072150 -
Journal of Agricultural and Food... Oct 2022Precipitation of bovine serum albumin (BSA) by 21 hydrolyzable tannins (HTs) and the characteristics of the insoluble complexes were studied stoichiometrically by...
Precipitation of bovine serum albumin (BSA) by 21 hydrolyzable tannins (HTs) and the characteristics of the insoluble complexes were studied stoichiometrically by ultra-performance liquid chromatography. With regard to HT monomers, the protein precipitation and the characteristic of the formed precipitates were unique for each studied HT and depended upon the functional groups present in the structures. The monomeric units comprising the oligomers formed the functional units important for the protein precipitation capacity, and small structural differences among the monomer units were less important than the overall oligomer size and flexibility. In addition, the greater tendency of certain HTs to form insoluble complexes when mixed with BSA was partially linked to the higher self-association and consequent stronger cooperative binding of these HTs with BSA.
Topics: Hydrolyzable Tannins; Serum Albumin, Bovine; Tannins
PubMed: 35708502
DOI: 10.1021/acs.jafc.2c01765 -
Nutrients Aug 2021The extract of pomegranate () has been applied in medicine since ancient times due to its broad-spectrum health-beneficial properties. It is a rich source of... (Review)
Review
The extract of pomegranate () has been applied in medicine since ancient times due to its broad-spectrum health-beneficial properties. It is a rich source of hydrolyzable tannins and anthocyanins, exhibiting strong antioxidative, anti-inflammatory, and antineoplastic properties. Anticancer activities of pomegranate with reference to modulated signaling pathways in various cancer diseases have been recently reviewed. However, less is known about punicalagin (Pug), a prevailing compound in pomegranate, seemingly responsible for its most beneficial properties. In this review, the newest data derived from recent scientific reports addressing Pug impact on neoplastic cells are summarized and discussed. Its attenuating effect on signaling circuits promoting cancer growth and invasion is depicted. The Pug-induced redirection of signal-transduction pathways from survival and proliferation into cell-cycle arrest, apoptosis, senescence, and autophagy (thus compromising neoplastic progression) is delineated. Considerations presented in this review are based mainly on data obtained from in vitro cell line models and concern the influence of Pug on human cervical, ovarian, breast, lung, thyroid, colorectal, central nervous system, bone, as well as other cancer types.
Topics: Antineoplastic Agents; Cell Physiological Phenomena; Humans; Hydrolyzable Tannins; Neoplasms; Plant Extracts; Pomegranate; Signal Transduction
PubMed: 34444893
DOI: 10.3390/nu13082733