1 616 143 BIOACTIVE COMPOUNDS IN OXIDATIVE STRESS-MEDIATED DISEASES: TARGETING THE NRF2/ARE SIGNALING PATHWAY AND EPIGENETIC REGULATION. OXIDATIVE STRESS IS A PATHOLOGICAL CONDITION OCCURRING DUE TO AN IMBALANCE BETWEEN THE OXIDANTS AND ANTIOXIDANT DEFENSE SYSTEMS IN THE BODY. NUCLEAR FACTOR E2-RELATED FACTOR 2 (NRF2), ENCODED BY THE GENE NFE2L2, IS THE MASTER REGULATOR OF PHASE II ANTIOXIDANT ENZYMES THAT PROTECT AGAINST OXIDATIVE STRESS AND INFLAMMATION. NRF2/ARE SIGNALING HAS BEEN CONSIDERED AS A PROMISING TARGET AGAINST OXIDATIVE STRESS-MEDIATED DISEASES LIKE DIABETES, FIBROSIS, NEUROTOXICITY, AND CANCER. THE CONSUMPTION OF DIETARY PHYTOCHEMICALS ACTS AS AN EFFECTIVE MODULATOR OF NRF2/ARE IN VARIOUS ACUTE AND CHRONIC DISEASES. IN THE PRESENT REVIEW, WE DISCUSSED THE ROLE OF NRF2 IN DIABETES, ALZHEIMER'S DISEASE (AD), PARKINSON'S DISEASE (PD), CANCER, AND ATHEROSCLEROSIS. ADDITIONALLY, WE DISCUSSED THE PHYTOCHEMICALS LIKE CURCUMIN, QUERCETIN, RESVERATROL, EPIGALLOCATECHIN GALLATE, APIGENIN, SULFORAPHANE, AND URSOLIC ACID THAT HAVE EFFECTIVELY MODIFIED NRF2 SIGNALING AND PREVENTED VARIOUS DISEASES IN BOTH IN VITRO AND IN VIVO MODELS. BASED ON THE LITERATURE, IT IS CLEAR THAT DIETARY PHYTOCHEMICALS CAN PREVENT DISEASES BY (1) BLOCKING OXIDATIVE STRESS-INHIBITING INFLAMMATORY MEDIATORS THROUGH INHIBITING KEAP1 OR ACTIVATING NRF2 EXPRESSION AND ITS DOWNSTREAM TARGETS IN THE NUCLEUS, INCLUDING HO-1, SOD, AND CAT; (2) REGULATING NRF2 SIGNALING BY VARIOUS KINASES LIKE GSK3BETA, PI3/AKT, AND MAPK; AND (3) MODIFYING EPIGENETIC MODULATION, SUCH AS METHYLATION, AT THE NRF2 PROMOTER REGION; HOWEVER, FURTHER INVESTIGATION INTO OTHER UPSTREAM SIGNALING MOLECULES LIKE NRF2 AND THE EFFECT OF PHYTOCHEMICALS ON THEM STILL NEED TO BE INVESTIGATED IN THE NEAR FUTURE. 2021 2 4534 38 MULTIPLE REGULATIONS OF KEAP1/NRF2 SYSTEM BY DIETARY PHYTOCHEMICALS. KEAP1/NRF2 SYSTEM PLAYS A CRITICAL ROLE ON CELLULAR PROTECTION BY REGULATING MANY ANTIOXIDANT AND DETOXIFICATION ENZYME GENES THROUGH THE ANTIOXIDANT RESPONSE ELEMENT (ARE). THUS, IT MUST WORK CONSTANTLY TO PREVENT THE ACCUMULATION OF REACTIVE OXYGEN SPECIES (ROS) BECAUSE EXCESS ROS ARE ASSOCIATED WITH MANY DISEASES SUCH AS CANCER, CARDIOVASCULAR COMPLICATIONS, INFLAMMATION, AND NEURODEGENERATION. DIETARY PHYTOCHEMICALS WIDELY DISTRIBUTING IN FRUITS AND VEGETABLES HAVE BEEN CONSIDERED TO POSSESS CANCER CHEMOPREVENTIVE POTENTIAL THROUGH THE INDUCTION OF KEAP1/NRF2 SYSTEM-MEDIATED ANTIOXIDANT AND DETOXIFICATION ENZYMES IN A VARIETY OF MANNERS. THE DATA ARE EXTENSIVE AND ARE NOT WELL CLASSIFIED ON THE MOLECULAR MECHANISMS. IN THIS REVIEW, WE FIRST BRIEFLY INTRODUCE THE CURRENT KNOWLEDGE ON KEAP1/NRF2 SYSTEM REGULATION INCLUDING KEAP1-DEPENDENT AND KEAP1-INDEPENDENT CASCADES, AND EPIGENETIC PATHWAY. THEN, WE SUMMARIZE THE MOLECULAR TARGETS OF KEAP1/NRF2 SYSTEM BY DIETARY PHYTOCHEMICALS, AND FINALLY REVIEW THE CROSSTALK BETWEEN KEAP1/NRF2 SYSTEM AND OTHER CELLULAR SIGNALING PATHWAYS TO REGULATE DIVERSE CHRONIC DISEASES BY DIETARY PHYTOCHEMICALS. THESE COMPREHENSIVE DATA WILL HELP US TO UNDERSTAND THE POTENTIAL EFFECTS OF DIETARY PHYTOCHEMICALS ON THE PREVENTION OF CHRONIC DISEASES AND MAINTENANCE OF HUMAN HEALTH. 2016 3 688 43 BRASSICA-DERIVED PLANT BIOACTIVES AS MODULATORS OF CHEMOPREVENTIVE AND INFLAMMATORY SIGNALING PATHWAYS. A HIGH CONSUMPTION OF VEGETABLES BELONGING TO THE BRASSICACEAE FAMILY HAS BEEN RELATED TO A LOWER INCIDENCE OF CHRONIC DISEASES INCLUDING DIFFERENT KINDS OF CANCER. THESE BENEFICIAL EFFECTS OF, E.G., BROCCOLI, CABBAGE OR ROCKET (ARUGULA) INTAKE HAVE BEEN MAINLY DEDICATED TO THE SULFUR-CONTAINING GLUCOSINOLATES (GLSS)-SECONDARY PLANT COMPOUNDS NEARLY EXCLUSIVELY PRESENT IN BRASSICACEAE-AND IN PARTICULAR TO THEIR BIOACTIVE BREAKDOWN PRODUCTS INCLUDING ISOTHIOCYANATES (ITCS). OVERALL, THE CURRENT LITERATURE INDICATE THAT SELECTED BRASSICA-DERIVED ITCS EXHIBIT HEALTH-PROMOTING EFFECTS IN VITRO, AS WELL AS IN LABORATORY MICE IN VIVO. SOME STUDIES SUGGEST ANTI-CARCINOGENIC AND ANTI-INFLAMMATORY PROPERTIES FOR ITCS WHICH MAY BE COMMUNICATED THROUGH AN ACTIVATION OF THE REDOX-SENSITIVE TRANSCRIPTION FACTOR NUCLEAR FACTOR ERYTHROID 2-RELATED FACTOR 2 (NRF2) THAT CONTROLS THE EXPRESSION OF ANTIOXIDANT AND PHASE II ENZYMES. FURTHERMORE, IT HAS BEEN SHOWN THAT ITCS ARE ABLE TO SIGNIFICANTLY AMELIORATE A SEVERE INFLAMMATORY PHENOTYPE IN COLITIC MICE IN VIVO. AS THERE ARE STUDIES AVAILABLE SUGGESTING AN EPIGENETIC MODE OF ACTION FOR BRASSICA-DERIVED PHYTOCHEMICALS, THE CONDUCTION OF FURTHER STUDIES WOULD BE RECOMMENDABLE TO INVESTIGATE IF THE BENEFICIAL EFFECTS OF THESE COMPOUNDS ALSO PERSIST DURING AN IRREGULAR CONSUMPTION PATTERN. 2017 4 3212 30 HEALTH PROMOTING EFFECTS OF BRASSICA-DERIVED PHYTOCHEMICALS: FROM CHEMOPREVENTIVE AND ANTI-INFLAMMATORY ACTIVITIES TO EPIGENETIC REGULATION. A HIGH INTAKE OF BRASSICA VEGETABLES MAY BE ASSOCIATED WITH A DECREASED CHRONIC DISEASE RISK. HEALTH PROMOTING EFFECTS OF BRASSICACEAE HAVE BEEN PARTLY ATTRIBUTED TO GLUCOSINOLATES AND IN PARTICULAR TO THEIR HYDROLYZATION PRODUCTS INCLUDING ISOTHIOCYANATES. IN VITRO AND IN VIVO STUDIES SUGGEST A CHEMOPREVENTIVE ACTIVITY OF ISOTHIOCYANATES THROUGH THE REDOX-SENSITIVE TRANSCRIPTION FACTOR NRF2. FURTHERMORE, STUDIES IN CULTURED CELLS, IN LABORATORY RODENTS, AND ALSO IN HUMANS SUPPORT AN ANTI-INFLAMMATORY EFFECT OF BRASSICA-DERIVED PHYTOCHEMICALS. HOWEVER, THE UNDERLYING MECHANISMS OF HOW THESE COMPOUNDS MEDIATE THEIR HEALTH PROMOTING EFFECTS ARE YET NOT FULLY UNDERSTOOD. RECENT FINDINGS SUGGEST THAT BRASSICA-DERIVED COMPOUNDS ARE REGULATORS OF EPIGENETIC MECHANISMS. IT HAS BEEN SHOWN THAT ISOTHIOCYANATES MAY INHIBIT HISTONE DEACETYLASE TRANSFERASES AND DNA-METHYLTRANSFERASES IN CULTURED CELLS. ONLY A FEW PAPERS HAVE DEALT WITH THE EFFECT OF BRASSICA-DERIVED COMPOUNDS ON EPIGENETIC MECHANISMS IN LABORATORY ANIMALS, WHEREAS DATA IN HUMANS ARE CURRENTLY LACKING. THE PRESENT REVIEW AIMS TO SUMMARIZE THE CURRENT KNOWLEDGE REGARDING THE BIOLOGICAL ACTIVITIES OF BRASSICA-DERIVED PHYTOCHEMICALS REGARDING CHEMOPREVENTIVE, ANTI-INFLAMMATORY, AND EPIGENETIC PATHWAYS. 2013 5 4792 43 NUTRITIONAL EPIGENETICS AND PHYTOCHEMICALS IN CANCER FORMATION. NUTRIGENETICS AND NUTRIGENOMICS ARE TWO CONCEPTS IN THE AREA OF NUTRITIONAL GENOMICS. EPIGENETICS IS A NEW DISCIPLINE WITH SIGNIFICANT POTENTIAL IN THE PREVENTION AND MANAGEMENT OF CERTAIN CARCINOMAS AND DISEASES. EPIGENETICS CONSISTS OF DNA METHYLATION, HISTONE MODIFICATION, NON-CODING RNAS, AND TELOMERASE ACTIVITY. EPIGENETIC-BASED MECHANISMS ACT ON THE INHIBITION OF CANCER CELLS BY MODULATING ENZYMES SUCH AS DNA METHYLTRANSFERASE AND HISTONE DEACETYLASE, AS WELL AS NON-CODING RNAS. PHYTOCHEMICALS ARE NATURAL BIOACTIVE COMPONENTS OF PLANT ORIGIN THAT HAVE ANTIOXIDANT, ANTI-INFLAMMATORY, AND ANTI-ANGIOGENIC EFFECTS ON VARIOUS DISEASES, ESPECIALLY CANCER. THE EPIGENETIC DIET IS A NUTRITIONAL MODEL BASED ON THE CONSUMPTION OF VARIOUS PHYTOCHEMICALS SUCH AS EPIGALLOCATECHIN-3-GALLATE, MORIN, CAFFEIC ACID PHENYL ESTER, APIGENIN, GENISTEIN, CURCUMIN, RESVERATROL, AND SULFORAPHANE. PHYTOCHEMICALS EXERT THEIR EFFECTS ON CANCER-BASED BY REDUCING CELL PROLIFERATION, INVASION, AND METASTASIS AND INCREASING CELL APOPTOSIS. SIMULTANEOUSLY, IT HAS FUNCTIONS SUCH AS REDUCING ONCOGENES THAT HAVE EFFECTS ON CANCER ETIOLOGY AND INCREASING TUMOR SUPPRESSOR GENES.KEY TEACHING POINTSCANCER IS A CHRONIC DISEASE WITH A HIGH MORTALITY RATE, IN WHICH VARIOUS GENETIC AND ENVIRONMENTAL FACTORS ARE INVOLVED IN ITS ETIOLOGY.PROTOONCOGENES, TUMOR SUPPRESSOR GENES, AND DNA REPAIR GENES ARE AMONG THE GENE GROUPS THAT FORM THE BASIS OF CANCER AND GENETIC STRUCTURE.THE BIDIRECTIONAL INTERACTION BETWEEN NUTRITION AND THE HUMAN GENOME HAS BEEN EFFECTIVE IN THE EMERGENCE OF THE CONCEPTS OF NUTRIGENETICS AND NUTRIGENOMICS.EPIGENETIC DIET IS A DIET BASED ON THE CONSUMPTION OF FOODS SUCH AS SOY, GRAPES, BLUEBERRIES, TURMERIC, CRUCIFEROUS VEGETABLES, AND GREEN TEA, WHICH INDUCE EPIGENETIC MECHANISMS THAT PROTECT AGAINST CANCER AND AGING. 2023 6 1416 49 DIETARY POLYPHENOLS REMODEL DNA METHYLATION PATTERNS OF NRF2 IN CHRONIC DISEASE. THE NUCLEAR FACTOR ERYTHROID 2-RELATED FACTOR 2 (NRF2) IS A TRANSCRIPTION FACTOR CRUCIAL IN REGULATING CELLULAR HOMEOSTASIS AND APOPTOSIS. THE NRF2 GENE HAS BEEN IMPLICATED IN VARIOUS BIOLOGICAL ACTIVITIES, INCLUDING ANTIOXIDANT, ANTI-INFLAMMATORY, AND ANTICANCER PROPERTIES. NRF2 CAN BE REGULATED GENETICALLY AND EPIGENETICALLY AT THE TRANSCRIPTIONAL, POST-TRANSCRIPTIONAL, AND TRANSLATIONAL LEVELS. ALTHOUGH DNA METHYLATION IS ONE OF THE CRITICAL BIOLOGICAL PROCESSES VITAL FOR GENE EXPRESSION, SOMETIMES, ANOMALOUS METHYLATION PATTERNS RESULT IN THE DYSREGULATION OF GENES AND CONSEQUENT DISEASES AND DISORDERS. SEVERAL STUDIES HAVE REPORTED PROMOTER HYPERMETHYLATION DOWNREGULATED NRF2 EXPRESSION AND ITS DOWNSTREAM TARGETS. IN CONTRAST TO THE UNALTERABLE NATURE OF GENETIC PATTERNS, EPIGENETIC CHANGES CAN BE REVERSED, OPENING UP NEW POSSIBILITIES IN DEVELOPING THERAPIES FOR VARIOUS METABOLIC DISORDERS AND DISEASES. THIS REVIEW DISCUSSES THE CURRENT STATE OF THE NRF2-MEDIATED ANTIOXIDATIVE AND CHEMOPREVENTIVE ACTIVITIES OF SEVERAL NATURAL PHYTOCHEMICALS, INCLUDING SULFORAPHANE, RESVERATROL, CURCUMIN, LUTEOLIN, COROSOLIC ACID, APIGENIN, AND MOST OTHER COMPOUNDS THAT HAVE BEEN FOUND TO ACTIVATE NRF2. THIS EPIGENETIC REVERSAL OF HYPERMETHYLATED NRF2 STATES PROVIDES NEW OPPORTUNITIES FOR RESEARCH INTO DIETARY PHYTOCHEMISTRY THAT AFFECTS THE HUMAN EPIGENOME AND THE POSSIBILITY FOR CUTTING-EDGE APPROACHES TO TARGET NRF2-MEDIATED SIGNALING TO PREVENT CHRONIC DISORDERS. 2023 7 1413 39 DIETARY PHYTOCHEMICALS AND CANCER CHEMOPREVENTION: A PERSPECTIVE ON OXIDATIVE STRESS, INFLAMMATION, AND EPIGENETICS. OXIDATIVE STRESS OCCURS WHEN CELLULAR REACTIVE OXYGEN SPECIES LEVELS EXCEED THE SELF-ANTIOXIDANT CAPACITY OF THE BODY. OXIDATIVE STRESS INDUCES MANY PATHOLOGICAL CHANGES, INCLUDING INFLAMMATION AND CANCER. CHRONIC INFLAMMATION IS BELIEVED TO BE STRONGLY ASSOCIATED WITH THE MAJOR STAGES OF CARCINOGENESIS. THE NUCLEAR FACTOR ERYTHROID 2-RELATED FACTOR 2 (NRF2) PATHWAY PLAYS A CRUCIAL ROLE IN REGULATING OXIDATIVE STRESS AND INFLAMMATION BY MANIPULATING KEY ANTIOXIDANT AND DETOXIFICATION ENZYME GENES VIA THE ANTIOXIDANT RESPONSE ELEMENT. MANY DIETARY PHYTOCHEMICALS WITH CANCER CHEMOPREVENTIVE PROPERTIES, SUCH AS POLYPHENOLS, ISOTHIOCYANATES, AND TRITERPENOIDS, EXERT ANTIOXIDANT AND ANTI-INFLAMMATORY FUNCTIONS BY ACTIVATING THE NRF2 PATHWAY. FURTHERMORE, EPIGENETIC CHANGES, INCLUDING DNA METHYLATION, HISTONE POST-TRANSLATIONAL MODIFICATIONS, AND MIRNA-MEDIATED POST-TRANSCRIPTIONAL ALTERATIONS, ALSO LEAD TO VARIOUS CARCINOGENESIS PROCESSES BY SUPPRESSING CANCER REPRESSOR GENE TRANSCRIPTION. USING EPIGENETIC RESEARCH TOOLS, INCLUDING NEXT-GENERATION SEQUENCING TECHNOLOGIES, MANY DIETARY PHYTOCHEMICALS ARE SHOWN TO MODIFY AND REVERSE ABERRANT EPIGENETIC/EPIGENOME CHANGES, POTENTIALLY LEADING TO CANCER PREVENTION/TREATMENT. THUS, THE BENEFICIAL EFFECTS OF DIETARY PHYTOCHEMICALS ON CANCER DEVELOPMENT WARRANT FURTHER INVESTIGATION TO PROVIDE ADDITIONAL IMPETUS FOR CLINICAL TRANSLATIONAL STUDIES. 2016 8 6290 34 THE POTENTIAL ROLE OF NUTRITIONAL GENOMICS TOOLS IN VALIDATING HIGH HEALTH FOODS FOR CANCER CONTROL: BROCCOLI AS EXAMPLE. NUTRITIONAL GENOMICS REFLECTS GENE/NUTRIENT INTERACTIONS, UTILISING HIGH-THROUGHPUT GENOMIC TOOLS IN NUTRITION RESEARCH. THE FIELD ALSO CONSIDERS THE CONTRIBUTION OF INDIVIDUAL GENOTYPES TO WELLNESS AND THE RISK OF CHRONIC DISEASE (NUTRIGENETICS), AND HOW SUCH GENETIC PREDISPOSITION MAY BE MODIFIED BY APPROPRIATE DIETS. FOR EXAMPLE, HIGH CONSUMPTION OF BRASSICACEOUS VEGETABLES, INCLUDING BROCCOLI, HAS REGULARLY ASSOCIATED WITH LOW CANCER RISK. BIOACTIVE CHEMICALS IN BROCCOLI INCLUDE GLUCOSINOLATES, PLANT PIGMENTS INCLUDING KAEMPFEROL, QUERCETIN, LUTEIN AND CAROTENOIDS, VARIOUS VITAMINS, MINERALS AND AMINO ACIDS. CANCER PREVENTION IS HYPOTHESISED TO ACT THROUGH VARIOUS MECHANISMS INCLUDING MODULATION OF XENOBIOTIC METABOLISING ENZYMES, NF-E2 P45-RELATED FACTOR-2 (NRF2)-MEDIATED STRESS-RESPONSE MECHANISMS, AND PROTECTION AGAINST GENOMIC INSTABILITY. BROCCOLI AND BROCCOLI EXTRACTS ALSO REGULATE THE PROGRESSION OF CANCER THROUGH ANTI-INFLAMMATORY EFFECTS, EFFECTS ON SIGNAL TRANSDUCTION, EPIGENETIC EFFECTS AND MODULATION OF THE COLONIC MICROFLORA. HUMAN INTERVENTION STUDIES WITH BROCCOLI AND RELATED FOODS, USING STANDARD BIOMARKER METHODOLOGIES, REVEAL PART OF A COMPLEX PICTURE. NUTRIGENOMIC APPROACHES, ESPECIALLY TRANSCRIPTOMICS, ENABLE SIMULTANEOUS STUDY OF VARIOUS SIGNALLING PATHWAYS AND NETWORKS. PHENOTYPIC, GENETIC AND/OR METABOLIC STRATIFICATION MAY IDENTIFY INDIVIDUALS MOST LIKELY TO RESPOND POSITIVELY TO FOODS OR DIETS. JOINTLY, THESE TECHNOLOGIES CAN PROVIDE PROOF OF HUMAN EFFICACY, AND MAY BE ESSENTIAL TO ENSURE EFFECTIVE MARKET TRANSFER AND UPTAKE OF BROCCOLI AND RELATED FOODS. 2012 9 4652 32 NEUROPROTECTION WITH NATURAL ANTIOXIDANTS AND NUTRACEUTICALS IN THE CONTEXT OF BRAIN CELL DEGENERATION: THE EPIGENETIC CONNECTION. BIOACTIVE ANTIOXIDANT AGENTS PRESENT IN SELECTED PLANTS ARE KNOWN TO PROVIDE THE FIRST LINE OF BIOLOGICAL DEFENSE AGAINST OXIDATIVE STRESS. IN PARTICULAR, SOLUBLE VITAMIN C, E, CAROTENOIDS AND PHENOLIC COMPOUNDS HAVE DEMONSTRATED CRUCIAL BIOLOGICAL EFFECTS IN CELLS AGAINST OXIDATIVE DAMAGE, PREVENTING PREVALENT CHRONIC DISEASES, SUCH AS DIABETES, CANCER AND CARDIOVASCULAR DISEASE. THE REPORTED WIDE RANGE OF EFFECTS THAT INCLUDED ANTI-AGING, ANTI-ATHEROSCLEROSIS, ANTI-INFLAMMATORY AND ANTICANCER ACTIVITY WERE STUDIED AGAINST DEGENERATIVE PATHOLOGIES OF THE BRAIN. VITAMINS AND DIFFERENT PHYTOCHEMICALS ARE IMPORTANT EPIGENETIC MODIFIERS THAT PREVENT NEURODEGENERATION. IN ORDER TO EXPLORE THE POTENTIAL ANTIOXIDANT SOURCES IN FUNCTIONAL FOODS AND NUTRACEUTICALS AGAINST NEURODEGENERATION, THE PRESENT PAPER AIMS TO SHOW A COMPREHENSIVE ASSESSMENT OF ANTIOXIDANT ACTIVITY AT CHEMICAL AND CELLULAR LEVELS. THE EFFECTS OF THE DIFFERENT BIOACTIVE COMPOUNDS AVAILABLE AND THEIR ANTIOXIDANT ACTIVITY THROUGH AN EPIGENETIC POINT OF VIEW ARE ALSO DISCUSSED. 2019 10 440 32 ANTIOXIDATIVE EFFECTS OF RHODIOLA GENUS: PHYTOCHEMISTRY AND PHARMACOLOGICAL MECHANISMS AGAINST THE DISEASES. RHODIOLA AS ONE OF TRADITIONAL MEDICINES HAS BEEN USED FOR CLINICAL TREATMENTS DUE TO ITS STRONG ANTIOXIDANT PROPERTIES. PHYTOCHEMICAL ANALYSIS REVEALED THE PRESENCE OF FLAVONOIDS, PHENYLPROPANOIDS, PHENYLETHANOL/BENZYL ALCOHOL DERIVATIVES, CYANOGENIC GLYCOSIDES AND TERPENOIDS. THE BIOACTIVE COMPOUNDS HAD BEEN DEMONSTRATED TO BE EFFECTIVE AT SCAVENGING REACTIVE OXYGEN SPECIES (ROS). THE STRUCTURES CONTAIN PHENOLIC HYDROXYL GROUPS AND UNSATURATED BONDS. THIS ARTICLE REVIEWS ANTIOXIDANT CAPACITIES OF THE EXTRACTS AND BIOACTIVE COMPONENTS DERIVED FROM RHODIOLA PLANTS. AS THE MAJOR PHARMACOLOGICAL INGREDIENT, SALIDROSIDE IS RIGOROUSLY INVESTIGATED AND USED IN SCIENTIFIC RESEARCHES AND CLINICAL PRACTICES. ACCUMULATED EVIDENCES INDICATED THAT EXTRACTS OF RHODIOLA PLANTS OR SALIDROSIDE COULD BE ABLE TO REVERSE DNA DAMAGE AND ALTER EXPRESSION OF CYTOKINES AND ANTIOXIDATIVE ENZYMES INDUCED BY ROS. THE UNDERLYING MECHANISMS FOR THE ANTIOXIDATIVE EFFECTS OF THE HERB HAVE BEEN INVESTIGATED IN THE LAST TWO DECADES. WE SUMMARIZE THE POSSIBLE EFFECTS AND ACTING PATHWAYS FOR THE HERB INVOLVED IN SEVERAL CHRONIC DISEASES IN CARDIOVASCULAR, RESPIRATORY, AND NERVOUS SYSTEMS, AS WELL AS POTENTIAL EPIGENETIC INFLUENCES. THE INFORMATION GENERATED FROM EXPERIMENTAL AND CLINICAL STUDIES OFFERED VALUABLE INSIGHTS FOR FURTHER INVESTIGATIONS OF MEDICAL POTENTIALS OF RHODIOLA PLANTS. 2017 11 4147 48 MECHANISMS UNDERLYING BIOLOGICAL EFFECTS OF CRUCIFEROUS GLUCOSINOLATE-DERIVED ISOTHIOCYANATES/INDOLES: A FOCUS ON METABOLIC SYNDROME. AN INVERSE CORRELATION BETWEEN VEGETABLE CONSUMPTION AND THE INCIDENCE OF CANCER HAS LONG BEEN DESCRIBED. THIS PROTECTIVE EFFECT IS STRONGER WHEN CRUCIFEROUS VEGETABLES ARE SPECIFICALLY CONSUMED. THE BENEFICIAL PROPERTIES OF VEGETABLES ARE ATTRIBUTED TO THEIR BIOACTIVE COMPONENTS LIKE FIBER, ANTIOXIDANTS VITAMINS, ANTIOXIDANTS, MINERALS, AND PHENOLIC COMPOUNDS. CRUCIFEROUS VEGETABLES CONTAIN ALL THESE MOLECULES; HOWEVER, WHAT MAKES THEM DIFFERENT ARE THEIR SULFUROUS COMPONENTS, CALLED GLUCOSINOLATES, RESPONSIBLE FOR THEIR SPECIAL SMELL AND TASTE. GLUCOSINOLATES ARE INACTIVE BIOLOGICALLY IN THE ORGANISM BUT ARE HYDROLYZED BY THE ENZYME MYROSINASE RELEASED AS A RESULT OF CHEWING, LEADING TO THE FORMATION OF ACTIVE DERIVATIVES SUCH AS ISOTHIOCYANATES AND INDOLES. A CONSIDERABLE NUMBER OF IN VITRO AND IN VIVO STUDIES HAVE REPORTED THAT ISOTHIOCYANATES AND INDOLES ELICIT CHEMOPREVENTIVE POTENCY THROUGH MULTIPLE MECHANISMS THAT INCLUDE MODULATION OF PHASES I AND II DETOXIFICATION PATHWAY ENZYMES, REGULATION OF CELL CYCLE ARREST, AND CONTROL OF CELL GROWTH, INDUCTION OF APOPTOSIS, ANTIOXIDANT ACTIVITY, ANTI-ANGIOGENIC EFFECTS, AND EPIGENETIC REGULATION. NUCLEAR ERYTHROID 2-RELATED FACTOR 2 (NRF2) AND NUCLEAR FACTOR-KAPPAB (NF-KAPPAB) ARE KEY AND CENTRAL REGULATORS IN ALL THESE PROCESSES WITH A MAIN ROLE IN OXIDATIVE STRESS AND INFLAMMATION CONTROL. IT HAS BEEN DESCRIBED THAT ISOTHIOCYANATES AND INDOLES REGULATE THEIR ACTIVITY DIRECTLY AND INDIRECTLY. TODAY, THE METABOLIC SYNDROME (CENTRAL OBESITY, INSULIN RESISTANCE, HYPERLIPIDEMIA, AND HYPERTENSION) IS RESPONSIBLE FOR A MAJORITY OF DEATHS WORLDWIDE. ALL COMPONENTS OF METABOLIC SYNDROME ARE CHARACTERIZED BY CHRONIC INFLAMMATION WITH DEREGULATION OF THE PI3K/AKT/MTOR, MAPK/EKR/JNK, NRF2, AND NF-KAPPAB SIGNALING PATHWAYS. THE EFFECTS OF GLSS DERIVATIVES CONTROLLING THESE PATHWAYS HAVE BEEN WIDELY DESCRIBED IN RELATION TO CANCER. CHANGES IN FOOD CONSUMPTION PATTERNS OBSERVED IN THE LAST DECADES TO HIGHER CONSUMPTION OF ULTRA-PROCESSED FOODS, WITH ELEVATION IN SIMPLE SUGAR AND SATURATED FAT CONTENTS AND LOWER CONSUMPTION OF VEGETABLES AND FRUITS HAVE BEEN DIRECTLY CORRELATED WITH METABOLIC SYNDROME PREVALENCE. IN THIS REVIEW, IT IS SUMMARIZED THE KNOWLEDGE REGARDING THE MECHANISMS BY WHICH CRUCIFEROUS GLUCOSINOLATE DERIVATIVES (ISOTHIOCYANATES AND INDOLES) DIRECTLY AND INDIRECTLY REGULATE THESE PATHWAYS. HOWEVER, THE REVIEW PLACES A SPECIAL FOCUS ON THE KNOWLEDGE OF THE EFFECTS OF GLUCOSINOLATES DERIVATIVES IN METABOLIC SYNDROME, SINCE THIS HAS NOT BEEN REVIEWED BEFORE. 2020 12 4396 33 MODULATION OF CHRONIC INFLAMMATION BY QUERCETIN: THE BENEFICIAL EFFECTS ON OBESITY. OBESITY HAS BECOME A MAJOR RISK FACTOR FOR THE DEVELOPMENT OF CHRONIC DISEASES SUCH AS INSULIN RESISTANCE, TYPE 2 DIABETES MELLITUS, AND CARDIOVASCULAR DISEASE. MOREOVER, OBESITY INDUCES CHRONIC INFLAMMATION IN ADIPOSE TISSUE, LIVER, SKELETAL MUSCLE, AND THE VASCULAR SYSTEM. QUERCETIN IS THE MAJOR REPRESENTATIVE OF THE FLAVONOID SUBCLASS OF FLAVONOLS, WHICH IS UBIQUITOUSLY CONTAINED WITHIN NATURAL PLANTS SUCH AS GREEN TEA, AND VEGETABLES, INCLUDING ONIONS AND APPLES. RESEARCHERS HAVE FOCUSED GREATER ATTENTION TO THE BENEFICIAL PHYSIOLOGICAL ROLES OF QUERCETIN, WHICH HAS ANTI-OXIDATIVE, ANTI-INFLAMMATORY, AND ANTI-FIBROTIC EFFECTS ON INSULIN RESISTANCE AND ATHEROSCLEROSIS IN OBESITY-RELATED DISEASES. ALSO, THE ANTI-INFLAMMATORY EFFECTS OF QUERCETIN ON INTESTINAL MICROBIOTA HAVE BEEN DEMONSTRATED IN OBESITY. IN ADDITION, THERE IS INCREASING EVIDENCE THAT QUERCETIN IS ASSOCIATED WITH EPIGENETIC ACTIVITIES IN CANCER, AND IN MATERNAL UNDERNUTRITION DURING GESTATION AND LACTATION. IN THIS REVIEW, WE FOCUS ON THE CHEMICAL PROPERTIES OF QUERCETIN, ITS DIETARY SOURCES IN OBESITY, AND ITS ANTI-INFLAMMATORY EFFECTS ON INSULIN RESISTANCE, ATHEROSCLEROSIS, INTESTINAL MICROBIOTA, AND MATERNAL UNDER-NUTRITION WITH EPIGENETIC ACTIVITY. 2020 13 6436 38 THERAPEUTIC ACTIONS OF TEA PHENOLIC COMPOUNDS AGAINST OXIDATIVE STRESS AND INFLAMMATION AS CENTRAL MEDIATORS IN THE DEVELOPMENT AND PROGRESSION OF HEALTH PROBLEMS: A REVIEW FOCUSING ON MICRORNA REGULATION. MANY HEALTH PROBLEMS INCLUDING CHRONIC DISEASES ARE CLOSELY ASSOCIATED WITH OXIDATIVE STRESS AND INFLAMMATION. TEA HAS ABUNDANT PHENOLIC COMPOUNDS WITH VARIOUS HEALTH BENEFITS INCLUDING ANTIOXIDANT AND ANTI-INFLAMMATORY PROPERTIES. THIS REVIEW FOCUSES ON THE PRESENT UNDERSTANDING OF THE IMPACT OF TEA PHENOLIC COMPOUNDS ON THE EXPRESSION OF MIRNAS, AND ELUCIDATES THE BIOCHEMICAL AND MOLECULAR MECHANISMS UNDERLYING THE TRANSCRIPTIONAL AND POST-TRANSCRIPTIONAL PROTECTIVE ACTIONS OF TEA PHENOLIC COMPOUNDS AGAINST OXIDATIVE STRESS- AND/OR INFLAMMATION-MEDIATED DISEASES. CLINICAL STUDIES SHOWED THAT DRINKING TEA OR TAKING CATECHIN SUPPLEMENT ON A DAILY BASIS PROMOTED THE ENDOGENOUS ANTIOXIDANT DEFENSE SYSTEM OF THE BODY WHILE INHIBITING INFLAMMATORY FACTORS. THE REGULATION OF CHRONIC DISEASES BASED ON EPIGENETIC MECHANISMS, AND THE EPIGENETIC-BASED THERAPIES INVOLVING DIFFERENT TEA PHENOLIC COMPOUNDS, HAVE BEEN INSUFFICIENTLY STUDIED. THE MOLECULAR MECHANISMS AND APPLICATION STRATEGIES OF MIR-27 AND MIR-34 INVOLVED IN OXIDATIVE STRESS RESPONSE AND MIR-126 AND MIR-146 INVOLVED IN INFLAMMATION PROCESS WERE PRELIMINARILY INVESTIGATED. SOME EMERGING EVIDENCE SUGGESTS THAT TEA PHENOLIC COMPOUNDS MAY PROMOTE EPIGENETIC CHANGES, INVOLVING NON-CODING RNA REGULATION, DNA METHYLATION, HISTONE MODIFICATION, UBIQUITIN AND SUMO MODIFICATIONS. HOWEVER, EPIGENETIC MECHANISMS AND EPIGENETIC-BASED DISEASE THERAPIES INVOLVING PHENOLIC COMPOUNDS FROM DIFFERENT TEAS, AND THE POTENTIAL CROSS-TALKS AMONG THE EPIGENETIC EVENTS, REMAIN UNDERSTUDIED. 2023 14 1397 31 DIET PHYTOCHEMICALS AND CUTANEOUS CARCINOMA CHEMOPREVENTION: A REVIEW. CUTANEOUS CARCINOMA, WHICH HAS OCCUPIED A PECULIAR PLACE AMONG WORLDWIDE POPULATIONS, IS COMMONLY RESPONSIBLE FOR THE CONSIDERABLY INCREASING MORBIDITY AND MORTALITY RATES. CURRENTLY AVAILABLE MEDICAL PROCEDURES FAIL TO COMPLETELY AVOID CUTANEOUS CARCINOMA DEVELOPMENT OR TO PREVENT MORTALITY. CANCER CHEMOPREVENTION, AS AN ALTERNATIVE STRATEGY, IS BEING CONSIDERED TO REDUCE THE INCIDENCE AND BURDEN OF CANCERS THROUGH CHEMICAL AGENTS. DERIVED FROM DIETARY FOODS, PHYTOCHEMICALS HAVE BECOME SAFE AND RELIABLE COMPOUNDS FOR THE CHEMOPREVENTION OF CUTANEOUS CARCINOMA BY RELIEVING MULTIPLE PATHOLOGICAL PROCESSES, INCLUDING OXIDATIVE DAMAGE, EPIGENETIC ALTERATION, CHRONIC INFLAMMATION, ANGIOGENESIS, ETC. IN THIS REVIEW, WE PRESENTED COMPREHENSIVE KNOWLEDGES, MAIN MOLECULAR MECHANISMS FOR THE INITIATION AND DEVELOPMENT OF CUTANEOUS CARCINOMA AS WELL AS EFFECTS OF VARIOUS DIET PHYTOCHEMICALS ON CHEMOPREVENTION. 2017 15 6362 32 THE ROLE OF ISOTHIOCYANATES AS CANCER CHEMO-PREVENTIVE, CHEMO-THERAPEUTIC AND ANTI-MELANOMA AGENTS. MANY STUDIES HAVE SHOWN EVIDENCE IN SUPPORT OF THE BENEFICIAL EFFECTS OF PHYTOCHEMICALS IN PREVENTING CHRONIC DISEASES, INCLUDING CANCER. AMONG SUCH PHYTOCHEMICALS, SULPHUR-CONTAINING COMPOUNDS (E.G., ISOTHIOCYANATES (ITCS)) HAVE RAISED SCIENTIFIC INTEREST BY EXERTING UNIQUE CHEMO-PREVENTIVE PROPERTIES AGAINST CANCER PATHOGENESIS. ITCS ARE THE MAJOR BIOLOGICALLY ACTIVE COMPOUNDS CAPABLE OF MEDIATING THE ANTICANCER EFFECT OF CRUCIFEROUS VEGETABLES. RECENTLY, MANY STUDIES HAVE SHOWN THAT A HIGHER INTAKE OF CRUCIFEROUS VEGETABLES IS ASSOCIATED WITH REDUCED RISK OF DEVELOPING VARIOUS FORMS OF CANCERS PRIMARILY DUE TO A PLURALITY OF EFFECTS, INCLUDING (I) METABOLIC ACTIVATION AND DETOXIFICATION, (II) INFLAMMATION, (III) ANGIOGENESIS, (IV) METASTASIS AND (V) REGULATION OF THE EPIGENETIC MACHINERY. IN THE CONTEXT OF HUMAN MALIGNANT MELANOMA, A NUMBER OF STUDIES SUGGEST THAT ITCS CAN CAUSE CELL CYCLE GROWTH ARREST AND ALSO INDUCE APOPTOSIS IN HUMAN MALIGNANT MELANOMA CELLS. ON SUCH BASIS, ITCS COULD SERVE AS PROMISING CHEMO-THERAPEUTIC AGENTS THAT COULD BE USED IN THE CLINICAL SETTING TO POTENTIATE THE EFFICACY OF EXISTING THERAPIES. 2019 16 2352 43 EPIGENETIC REGULATION OF NRF2/KEAP1 BY PHYTOCHEMICALS. EPIGENETICS HAS PROVIDED A NEW DIMENSION TO OUR UNDERSTANDING OF NUCLEAR FACTOR ERYTHROID 2-RELATED FACTOR 2/KELCH-LIKE ECH-ASSOCIATED PROTEIN 1 (HUMAN NRF2/KEAP1 AND MURINE NRF2/KEAP1) SIGNALING. UNLIKE THE GENETIC CHANGES AFFECTING DNA SEQUENCE, THE REVERSIBLE NATURE OF EPIGENETIC ALTERATIONS PROVIDES AN ATTRACTIVE AVENUE FOR CANCER INTERCEPTION. THUS, TARGETING EPIGENETIC MECHANISMS IN THE CORRESPONDING SIGNALING NETWORKS REPRESENTS AN ENTICING STRATEGY FOR THERAPEUTIC INTERVENTION WITH DIETARY PHYTOCHEMICALS ACTING AT TRANSCRIPTIONAL, POST-TRANSCRIPTIONAL, AND POST-TRANSLATIONAL LEVELS. THIS REGULATION INVOLVES THE INTERPLAY OF HISTONE MODIFICATIONS AND DNA METHYLATION STATES IN THE HUMAN NFE2L2/KEAP1 AND MURINE NFE2L2/KEAP1 GENES, ACETYLATION OF LYSINE RESIDUES IN NRF2 AND NRF2, INTERACTION WITH BROMODOMAIN AND EXTRATERMINAL DOMAIN (BET) ACETYL "READER" PROTEINS, AND NON-CODING RNAS SUCH AS MICRORNA (MIRNA) AND LONG NON-CODING RNA (LNCRNA). PHYTOCHEMICALS DOCUMENTED TO MODULATE NRF2 SIGNALING ACT BY REVERSING HYPERMETHYLATED STATES IN THE CPG ISLANDS OF NFE2L2 OR NFE2L2, VIA THE INHIBITION OF DNA METHYLTRANSFERASES (DNMTS) AND HISTONE DEACETYLASES (HDACS), THROUGH THE INDUCTION OF TEN-ELEVEN TRANSLOCATION (TET) ENZYMES, OR BY INDUCING MIRNA TO TARGET THE 3'-UTR OF THE CORRESPONDING MRNA TRANSCRIPTS. TO DATE, FEWER THAN TWENTY PHYTOCHEMICALS HAVE BEEN REPORTED AS NRF2 EPIGENETIC MODIFIERS, INCLUDING CURCUMIN, SULFORAPHANE, RESVERATROL, RESERPINE, AND URSOLIC ACID. THIS OPENS AVENUES FOR EXPLORING ADDITIONAL DIETARY PHYTOCHEMICALS THAT REGULATE THE HUMAN EPIGENOME, AND THE POTENTIAL FOR NOVEL STRATEGIES TO TARGET NRF2 SIGNALING WITH A VIEW TO BENEFICIAL INTERCEPTION OF CANCER AND OTHER CHRONIC DISEASES. 2020 17 617 36 BIOACTIVE FOOD COMPOUNDS, EPIGENETICS AND CHRONIC DISEASE PREVENTION: FOCUS ON EARLY-LIFE INTERVENTIONS WITH POLYPHENOLS. CONSUMPTION OF BIOACTIVE COMPOUNDS SUCH AS POLYPHENOLS, ISOTHIOCYANATES, SULFUR-CONTAINING COMPOUNDS AND TERPENOIDS, FOUND IN FRUITS AND VEGETABLES, IS ASSOCIATED WITH PREVENTION OF CHRONIC DISEASE. THESE BIOACTIVE FOOD COMPOUNDS ELICIT THEIR PROTECTIVE EFFECTS THROUGH COMPLEX MECHANISMS AT THE CELLULAR AND MOLECULAR, INCLUDING EPIGENETIC LEVELS. ACCORDING TO THE DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE (DOHAD) PARADIGM, IN UTERO EXPOSURE TO STRESSORS SUCH AS MALNUTRITION THROUGH MATERNAL DIET WOULD IMPAIR FETAL DEVELOPMENT AND EPIGENETICALLY PROGRAM INCREASED RISK OF METABOLIC DISEASES AND SOME CANCERS IN ADULT LIFE. IN ADDITION, A ROLE FOR FATHERS DIET DURING PRECONCEPTION ON THEIR OFFSPRING HEALTH AND CHRONIC DISEASE SUSCEPTIBILITY HAS ALSO EMERGED. THIS HIGHLIGHTS EARLY LIFE AS A PROMISING WINDOW OF OPPORTUNITY FOR STARTING DIETARY INTERVENTIONS FOCUSING ON PREVENTING CHRONIC DISEASES. HOWEVER, KNOWLEDGE ON THE POTENTIAL BENEFICIAL IMPACT OF EARLY LIFE EXPOSURE TO BIOACTIVE FOOD COMPOUNDS IS LIMITED. AMONG THE STUDIES THAT HAVE INVESTIGATED BIOACTIVE FOOD COMPOUNDS IN THE CONTEXT OF DOHAD, MOST HAVE FOCUSED ON THE IMPACT OF DIETARY POLYPHENOLS. THUS, IN THIS REVIEW WE DISCUSS EXPERIMENTAL EVIDENCE SUPPORTING A ROLE FOR THE DIETARY POLYPHENOLS RESVERATROL, GENISTEIN, EPIGALLOCATECHIN-3-GALLATE AND ANTHOCYANINS IN CHRONIC DISEASE PREVENTION CONSIDERING A PERSPECTIVE FROM EARLY-LIFE INTERVENTIONS THROUGH MATERNAL AND PATERNAL DIETS AND FOCUSING ON EPIGENETICS AS A POTENTIAL UNDERLYING MECHANISM. 2019 18 1414 34 DIETARY PHYTOCHEMICALS IN NEUROIMMUNOAGING: A NEW THERAPEUTIC POSSIBILITY FOR HUMANS? ALTHOUGH SEVERAL EFFORTS HAVE BEEN MADE IN THE SEARCH FOR GENETIC AND EPIGENETIC PATTERNS LINKED TO DISEASES, A COMPREHENSIVE EXPLANATION OF THE MECHANISMS UNDERLYING PATHOLOGICAL PHENOTYPIC PLASTICITY IS STILL FAR FROM BEING CLARIFIED. OXIDATIVE STRESS AND INFLAMMATION ARE TWO OF THE MAJOR TRIGGERS OF THE EPIGENETIC ALTERATIONS OCCURRING IN CHRONIC PATHOLOGIES, SUCH AS NEURODEGENERATIVE DISEASES. IN FACT, OVER THE LAST DECADE, REMARKABLE PROGRESS HAS BEEN MADE TO REALIZE THAT CHRONIC, LOW-GRADE INFLAMMATION IS ONE OF THE MAJOR RISK FACTOR UNDERLYING BRAIN AGING. ACCUMULATED DATA STRONGLY SUGGEST THAT PHYTOCHEMICALS FROM FRUITS, VEGETABLES, HERBS, AND SPICES MAY EXERT RELEVANT IMMUNOMODULATORY AND/OR ANTI-INFLAMMATORY ACTIVITIES IN THE CONTEXT OF BRAIN AGING. STARTING BY THE EVIDENCE THAT A COMMON DENOMINATOR OF AGING AND CHRONIC DEGENERATIVE DISEASES IS REPRESENTED BY INFLAMMATION, AND THAT SEVERAL DIETARY PHYTOCHEMICALS ARE ABLE TO POTENTIALLY INTERFERE WITH AND REGULATE THE NORMAL FUNCTION OF CELLS, IN PARTICULAR NEURONAL COMPONENTS, AIM OF THIS REVIEW IS TO SUMMARIZE RECENT STUDIES ON NEUROINFLAMMAGING PROCESSES AND PROOFS INDICATING THAT SPECIFIC PHYTOCHEMICALS MAY ACT AS POSITIVE MODULATORS OF NEUROINFLAMMATORY EVENTS. IN ADDITION, CRITICAL PATHWAYS INVOLVED IN MEDIATING PHYTOCHEMICALS EFFECTS ON NEUROINFLAMMAGING WERE DISCUSSED, EXPLORING THE REAL IMPACT OF THESE COMPOUNDS IN PRESERVING BRAIN HEALTH BEFORE THE ONSET OF SYMPTOMS LEADING TO INFLAMMATORY NEURODEGENERATION AND COGNITIVE DECLINE. 2016 19 3689 33 INFLAMMATORY AUTO-IMMUNE DISEASES OF THE INTESTINE AND THEIR MANAGEMENT BY NATURAL BIOACTIVE COMPOUNDS. AUTOIMMUNE DISEASES ARE CAUSED BY THE OVERACTIVITY OF THE IMMUNE SYSTEM TOWARDS SELF-CONSTITUENTS. RISK FACTORS OF AUTOIMMUNE DISEASES ARE MULTIPLE AND INCLUDE GENETIC, EPIGENETIC, ENVIRONMENTAL, AND PSYCHOLOGICAL. AUTOIMMUNE CHRONIC INFLAMMATORY BOWEL DISEASES, INCLUDING CELIAC AND INFLAMMATORY DISEASES (CROHN'S DISEASE AND ULCERATIVE COLITIS), CONSTITUTE A SIGNIFICANT HEALTH PROBLEM WORLDWIDE. BESIDES THE COMPLEXITY OF THE SYMPTOMS OF THESE DISEASES, THEIR TREATMENTS HAVE ONLY BEEN PALLIATIVE. NUMEROUS INVESTIGATIONS SHOWED THAT NATURAL PHYTOCHEMICALS COULD BE PROMISING STRATEGIES TO FIGHT AGAINST THESE AUTOIMMUNE DISEASES. IN THIS RESPECT, PLANT-DERIVED NATURAL COMPOUNDS SUCH AS FLAVONOIDS, PHENOLIC ACIDS, AND TERPENOIDS EXHIBITED SIGNIFICANT EFFECTS AGAINST THREE AUTOIMMUNE DISEASES AFFECTING THE INTESTINE, PARTICULARLY BOWEL DISEASES. THIS REVIEW FOCUSES ON THE ROLE OF NATURAL COMPOUNDS OBTAINED FROM MEDICINAL PLANTS IN MODULATING INFLAMMATORY AUTO-IMMUNE DISEASES OF THE INTESTINE. IT COVERS THE MOST RECENT LITERATURE RELATED TO THE EFFECT OF THESE NATURAL COMPOUNDS IN THE TREATMENT AND PREVENTION OF AUTO-IMMUNE DISEASES OF THE INTESTINE. 2022 20 2100 33 EPIGENETIC EFFECTS OF NATURAL POLYPHENOLS: A FOCUS ON SIRT1-MEDIATED MECHANISMS. POLYPHENOLS ARE A CLASS OF NATURAL COMPOUNDS WIDELY DISTRIBUTED IN FRUITS, VEGETABLES, AND PLANTS. THEY HAVE BEEN REPORTED TO POSSESS A WIDE RANGE OF ACTIVITIES IN PREVENTION AND ALLEVIATION OF VARIOUS DISEASES LIKE CANCER, NEUROINFLAMMATION, DIABETES, AND AGING. POLYPHENOLS ARE EFFECTIVE AGAINST CHRONIC DISEASES AND RECENT REPORTS INDICATED STRONG EPIGENETIC EFFECTS OF POLYPHENOLS. MOST OF THE STUDIES INVESTIGATING EPIGENETIC EFFECTS OF NATURAL POLYPHENOLS HAVE FOCUSED ON THEIR BENEFICIAL EFFECTS IN CANCER TREATMENT. HOWEVER, EPIGENETIC DEFECTS HAVE BEEN DEMONSTRATED IN MANY OTHER DISEASES AS WELL, AND APPLICATION OF POLYPHENOLS TO MODULATE THE EPIGENOME IS BECOMING AN INTERESTING FIELD OF RESEARCH. THIS REVIEW SUMMARIZES THE EFFECTS OF NATURAL POLYPHENOLS IN MODULATING EPIGENETIC-RELATED ENZYMES AS WELL AS THEIR EFFECT IN PREVENTION AND TREATMENT OF CHRONIC DISEASES WITH A FOCUS ON SIRT1 MODULATION. WE HAVE ALSO DISCUSSED THE RELATION BETWEEN THE STRUCTURE AND FUNCTION OF EPIGENETIC-MODIFYING POLYPHENOLS. 2014