1 5145 145 POTENTIAL ROLE OF NUTRACEUTICALS VIA TARGETING A WNT/BETA-CATENIN AND NF-KAPPAB PATHWAY IN TREATMENT OF OSTEOARTHRITIS. OSTEOARTHRITIS (OA) IS A DISEASE DUE TO THE AGING OF THE ARTICULAR CARTILAGE, A POST-MITOTIC TISSUE THAT STAYS FUNCTIONING UNTIL PRIMARY HOMEOSTATIC PROCESSES FAIL. BECAUSE OF PAIN AND DISABILITY, OA SIGNIFICANTLY INFLUENCES NATIONAL HEALTHCARE EXPENSES AND PATIENT QUALITY OF LIFE. IT IS A WHOLE-JOINT ILLNESS CHARACTERIZED BY INFLAMMATORY AND OXIDATIVE SIGNALING PATHWAYS AND SIGNIFICANT EPIGENETIC ALTERATIONS THAT CAUSE CARTILAGE EXTRACELLULAR MATRIX DEGRADATION. THE CANONICAL WNT PATHWAY (WNT/BETA-CATENIN PATHWAY) AND NUCLEAR FACTOR KAPPA B (NF-KAPPAB) SIGNALING PATHWAYS MAY FUNCTION IN JOINT TISSUES BY MODULATING THE ACTIVITY OF SYNOVIAL CELLS, OSTEOBLASTS, AND CHONDROCYTES. HOWEVER, FINDING INNOVATIVE WAYS TO TREAT OSTEOARTHRITIS AND GET THE JOINT BACK TO AVERAGE BALANCE IS STILL A STRUGGLE. NUTRACEUTICALS ARE DIETARY SUPPLEMENTS THAT PROMOTE JOINT HEALTH BY BALANCING ANABOLIC AND CATABOLIC SIGNALS. NEW THERAPEUTIC METHODS FOR OA TREATMENT HAVE BEEN DEVELOPED BASED ON MANY RESEARCH FINDINGS THAT SHOW NUTRACEUTICALS HAVE STRONG ANTI-INFLAMMATION, ANTIOXIDANT, ANTI-BONE RESORPTION, AND ANABOLIC PROPERTIES. FOR THE TREATMENT OF OSTEOARTHRITIS, WE EXPLORE THE POSSIBLE INVOLVEMENT OF NUTRACEUTICALS THAT TARGET THE WNT/BETA-CATENIN AND NF-KAPPAB PATHWAYS. PRACTICAL APPLICATIONS: IN KEEPING WITH THE AGING POPULATION, OSTEOARTHRITIS IS BECOMING MORE WIDESPREAD. IN THIS EXTENSIVE RESEARCH, WE STUDIED THE ROLE OF THE WNT/BETA-CATENIN AND NF-KAPPAB PATHWAY IN OA FORMATION AND PROGRESSION. NUTRACEUTICALS THAT TARGET THESE OA-RELATED SIGNALING PATHWAYS ARE A VIABLE THERAPY OPTION. WNT/BETA-CATENIN AND NF-KAPPAB SIGNALING PATHWAY ARE INHIBITED BY POLYPHENOLS, FLAVONOIDS, ALKALOIDS, AND VITAMINS FROM THE NUTRACEUTICAL CATEGORY, MAKING THEM POSSIBLE THERAPEUTIC DRUGS FOR OA THERAPY. 2022 2 4652 24 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 3 4777 28 NUTRACEUTICALS AND NETWORK PHARMACOLOGY APPROACH FOR ACUTE KIDNEY INJURY: A REVIEW FROM THE DRUG DISCOVERY ASPECT. ACUTE KIDNEY INJURY (AKI) HAS BECOME A GLOBAL HEALTH ISSUE, WITH APPROXIMATELY 12 MILLION REPORTS YEARLY, RESULTING IN A PERSISTENT INCREASE IN MORBIDITY AND MORTALITY RATES. AKI PATHOPHYSIOLOGY IS MULTIFACTORIAL INVOLVING OXIDATIVE STRESS, MITOCHONDRIAL DYSFUNCTION, EPIGENETIC MODIFICATIONS, INFLAMMATION, AND EVENTUALLY, CELL DEATH. HENCE, THERAPIES ABLE TO TARGET MULTIPLE PATHOMECHANISMS CAN AID IN AKI MANAGEMENT. TO CHANGE THE DRUG DISCOVERY FRAMEWORK FROM "ONE DRUG, ONE TARGET" TO "MULTICOMPONENT, MULTITARGET," NETWORK PHARMACOLOGY IS EVOLVING AS A NEXT-GENERATION RESEARCH APPROACH. RESEARCHERS HAVE USED THE NETWORK PHARMACOLOGY APPROACH TO PREDICT THE ROLE OF NUTRACEUTICALS AGAINST DIFFERENT AILMENTS INCLUDING AKI. NUTRACEUTICALS (HERBAL PRODUCTS, ISOLATED NUTRIENTS, AND DIETARY SUPPLEMENTS) BELONG TO THE PIONEERING CATEGORY OF NATURAL PRODUCTS AND HAVE SHOWN PROTECTIVE ACTION AGAINST AKI. NUTRACEUTICALS HAVE RECENTLY DRAWN ATTENTION BECAUSE OF THEIR ABILITY TO PROVIDE PHYSIOLOGICAL BENEFITS WITH LESS TOXIC EFFECTS. THIS REVIEW EMPHASIZES THE NUTRACEUTICALS THAT EXHIBITED RENOPROTECTION AGAINST AKI AND CAN BE USED EITHER AS MONOTHERAPY OR ADJUVANT WITH CONVENTIONAL THERAPIES TO BOOST THEIR EFFECTIVENESS AND LESSEN THE ADVERSE EFFECTS. ADDITIONALLY, THE STUDY SHEDS LIGHT ON THE APPLICATION OF NETWORK PHARMACOLOGY AS A COST-EFFECTIVE AND TIME-SAVING APPROACH FOR THE THERAPEUTIC TARGET PREDICTION OF NUTRACEUTICALS AGAINST AKI. 2023 4 6872 32 [POLYPHENOLS AS PROMISING BIOACTIVE COMPOUNDS]. POLYPHENOLS ARE DIVERSE AND WIDESPREAD BIOACTIVE PLANT-BASED COMPOUNDS. THESE COMPOUNDS ARE FOUND IN VARIOUS FOODS SUCH AS BERRIES, FRUITS, VEGETABLES, CEREALS, NUTS, COFFEE, CACAO, SPICES, SEEDS. THEY ARE DIVIDED INTO PHENOLIC ACIDS, STILBENES, FLAVONOIDS, LIGNANS DEPENDING ON THEIR MOLECULAR STRUCTURE. THEY ATTRACT THE ATTENTION OF RESEARCHERS DUE TO WIDE RANGE OF BIOLOGICAL EFFECTS ON HUMAN BODY. THE PURPOSE OF THIS WORK WAS TO ANALYZE MODERN SCIENTIFIC PUBLICATIONS ON THE BIOLOGICAL EFFECTS OF POLYPHENOLS. MATERIAL AND METHODS. THE REVIEW IS BASED ON PUBLICATIONS PRESENTED IN THE PUBMED, GOOGLE SCHOLAR, RESEARCHGATE, ELSEVIER, ELIBRARY, CYBERLENINKA DATABASES USING "POLYPHENOLS", "FLAVONOIDS", "RESVERATROL", "QUERCETIN", "CATECHINS" AS KEY WORDS. PREFERENCE WAS GIVEN TO ORIGINAL RESEARCHES OVER THE PAST 10 YEARS PUBLISHED IN REFEREED JOURNALS. RESULTS. OXIDATIVE STRESS, CHRONIC INFLAMMATION, MICROBIOME DISORDERS, INSULIN RESISTANCE, EXCESSIVE PROTEIN GLYCATION, AND GENOTOXIC EFFECTS ARE AT THE HEART OF THE PATHOGENESIS OF MANY DISEASES, INCLUDING THOSE ASSOCIATED WITH AGE. A LARGE AMOUNT OF MATERIAL HAS BEEN ACCUMULATED ON THE ANTIOXIDANT, ANTICARCINOGENIC, EPIGENETIC, METABOLIC, GEROPROTECTIVE, ANTI-INFLAMMATORY AND ANTIVIRAL EFFECTS OF POLYPHENOLS. THIS GIVES REASONS TO CONSIDER POLYPHENOLS AS VERY PROMISING MICRONUTRIENTS, WHICH INCLUSION IN THE DIET CAN REDUCE THE RISK OF DEVELOPING CARDIOVASCULAR, ONCOLOGICAL, NEURODEGENERATIVE DISEASES, DIABETES MELLITUS, OBESITY, METABOLIC SYNDROME, PREMATURE AGING, THAT IS, THE MAIN CAUSES OF DEATH, A DECREASE IN THE DURATION AND QUALITY OF LIFE OF A MODERN PERSON. CONCLUSION. EXPANDING THE RANGE OF PRODUCTS ENRICHED WITH POLYPHENOLS WITH THEIR HIGH BIOAVAILABILITY IS A PROMISING AREA OF SCIENTIFIC RESEARCH AND DEVELOPMENT OF PRODUCTION IN ORDER TO PREVENT SOCIALLY SIGNIFICANT AGE-ASSOCIATED DISEASES. 2023 5 4776 52 NUTRACEUTICAL ACTIVITY IN OSTEOARTHRITIS BIOLOGY: A FOCUS ON THE NUTRIGENOMIC ROLE. OSTEOARTHRITIS (OA) IS A DISEASE ASSOCIATED TO AGE OR CONDITIONS THAT PRECIPITATE AGING OF ARTICULAR CARTILAGE, A POST-MITOTIC TISSUE THAT REMAINS FUNCTIONAL UNTIL THE FAILURE OF MAJOR HOMEOSTATIC MECHANISMS. OA SEVERELY IMPACTS THE NATIONAL HEALTH SYSTEM COSTS AND PATIENTS' QUALITY OF LIFE BECAUSE OF PAIN AND DISABILITY. IT IS A WHOLE-JOINT DISEASE SUSTAINED BY INFLAMMATORY AND OXIDATIVE SIGNALING PATHWAYS AND MARKED EPIGENETIC CHANGES RESPONSIBLE FOR CATABOLISM OF THE CARTILAGE EXTRACELLULAR MATRIX. OA USUALLY PROGRESSES UNTIL ITS SEVERITY REQUIRES JOINT ARTHROPLASTY. TO DELAY THIS PROGRESSION AND TO IMPROVE SYMPTOMS, A WIDE RANGE OF NATURALLY DERIVED COMPOUNDS HAVE BEEN PROPOSED AND ARE SUMMARIZED IN THIS REVIEW. PRECLINICAL IN VITRO AND IN VIVO STUDIES HAVE PROVIDED PROOF OF PRINCIPLE THAT MANY OF THESE NUTRACEUTICALS ARE ABLE TO EXERT PLEIOTROPIC AND SYNERGISTIC EFFECTS AND EFFECTIVELY COUNTERACT OA PATHOGENESIS BY EXERTING BOTH ANTI-INFLAMMATORY AND ANTIOXIDANT ACTIVITIES AND BY TUNING MAJOR OA-RELATED SIGNALING PATHWAYS. THE LATTER ARE THE BASIS FOR THE NUTRIGENOMIC ROLE PLAYED BY SOME OF THESE COMPOUNDS, GIVEN THE MARKED CHANGES IN THE TRANSCRIPTOME, MIRNOME, AND METHYLOME. ONGOING AND FUTURE CLINICAL TRIALS WILL HOPEFULLY CONFIRM THE DISEASE-MODIFYING ABILITY OF THESE BIOACTIVE MOLECULES IN OA PATIENTS. 2020 6 5541 29 ROLE OF DIETARY PHENOLS IN MITIGATING MICROGLIA-MEDIATED NEUROINFLAMMATION. CHRONIC NEUROINFLAMMATION IS A PATHOLOGICAL FEATURE OF A NUMBER OF CENTRAL NERVOUS SYSTEM (CNS) DISEASES AND IS MEDIATED BY SUSTAINED ACTIVATION OF MICROGLIAL CELLS, THE INNATE IMMUNE CELLS OF THE CNS. STUDIES HAVE MAINLY FOCUSED ON IDENTIFYING THE MOLECULAR AND EPIGENETIC MECHANISMS OF MICROGLIAL ACTIVATION. THIS IS CRUCIAL IN DESIGNING THERAPEUTIC STRATEGIES FOR NEUROPATHOLOGIES IN WHICH PROLONGED MICROGLIAL ACTIVATION IS KNOWN TO EXACERBATE DISEASE CONDITION. IN RECENT YEARS, INCREASING EVIDENCE SHOW THAT NATURALLY OCCURRING COMPOUNDS PRESENT IN REGULAR DIET COULD FUNCTION AS "NUTRACEUTICALS," ARRESTING MICROGLIAL ACTIVATION, AND THUS CONFERRING NEUROPROTECTION. THIS REVIEW SUMMARIZES OUR UNDERSTANDING OF THE ROLE OF DIETARY PHENOLIC NUTRACEUTICALS IN MITIGATING MICROGLIA-MEDIATED NEUROINFLAMMATION. STUDIES SHOW THAT THESE NATURAL PHENOLS INHIBIT KEY SIGNALING PATHWAYS IN ACTIVATED MICROGLIA SUCH AS THE NFKAPPAB, MAPK AND JAK-STAT THAT TRIGGER MICROGLIA-MEDIATED INFLAMMATION IN VARIOUS NEUROPATHOLOGICAL CONDITIONS SUCH AS INJURY, INFECTION, STROKE, AUTISM AND NEURODEGENERATIVE DISEASES, I.E., ALZHEIMER'S DISEASE AND PARKINSON'S DISEASE. THE ANTI-INFLAMMATORY AND ANTIOXIDANT EFFECT EXERTED BY THESE NATURAL PHENOLS HAVE SHOWN CONSIDERABLE SUCCESS IN IMPROVING DISEASE CONDITION IN ANIMAL MODELS OF NEUROPATHOLOGIES, AND THUS SEEM TO BE SUITABLE CANDIDATES FOR DEVELOPING THERAPEUTIC STRATEGIES. 2016 7 1402 27 DIETARY ANTIOXIDANTS REMODEL DNA METHYLATION PATTERNS IN CHRONIC DISEASE. CHRONIC DISEASES ACCOUNT FOR OVER 60% OF ALL DEATHS WORLDWIDE ACCORDING TO THE WORLD HEALTH ORGANIZATION REPORTS. MAJORITY OF CASES ARE TRIGGERED BY ENVIRONMENTAL EXPOSURES THAT LEAD TO ABERRANT CHANGES IN THE EPIGENOME, SPECIFICALLY, THE DNA METHYLATION PATTERNS. THESE CHANGES RESULT IN ALTERED EXPRESSION OF GENE NETWORKS AND ACTIVITY OF SIGNALLING PATHWAYS. DIETARY ANTIOXIDANTS, INCLUDING CATECHINS, FLAVONOIDS, ANTHOCYANINS, STILBENES AND CAROTENOIDS, DEMONSTRATE BENEFITS IN THE PREVENTION AND/OR SUPPORT OF THERAPY IN CHRONIC DISEASES. THIS REVIEW PROVIDES A COMPREHENSIVE DISCUSSION OF POTENTIAL EPIGENETIC MECHANISMS OF ANTIOXIDANT COMPOUNDS IN REVERSING ALTERED PATTERNS OF DNA METHYLATION IN CHRONIC DISEASE. ANTIOXIDANTS REMODEL THE DNA METHYLATION PATTERNS THROUGH MULTIPLE MECHANISMS, INCLUDING REGULATION OF EPIGENETIC ENZYMES AND CHROMATIN REMODELLING COMPLEXES. THESE EFFECTS CAN FURTHER CONTRIBUTE TO ANTIOXIDANT PROPERTIES OF THE COMPOUNDS. ON THE OTHER HAND, DECREASE IN OXIDATIVE STRESS ITSELF CAN IMPACT DNA METHYLATION DELIVERING ADDITIONAL LINK BETWEEN ANTIOXIDANT MECHANISMS AND EPIGENETIC EFFECTS OF THE COMPOUNDS. LINKED ARTICLES: THIS ARTICLE IS PART OF A THEMED SECTION ON THE PHARMACOLOGY OF NUTRACEUTICALS. TO VIEW THE OTHER ARTICLES IN THIS SECTION VISIT HTTP://ONLINELIBRARY.WILEY.COM/DOI/10.1111/BPH.V177.6/ISSUETOC. 2020 8 1836 23 EFFECTS OF NUTRIENT AND BIOACTIVE FOOD COMPONENTS ON ALZHEIMER'S DISEASE AND EPIGENETIC. ALZHEIMER'S DISEASE (AD) IS THE MOST COMMON FORM OF DEMENTIA IN THE ELDERLY AND IS A CHRONIC NEURODEGENERATIVE DISEASE THAT IS BECOMING WIDESPREAD. FOR THIS REASON, IN RECENT YEARS FACTORS AFFECTING THE DEVELOPMENT, PROGRESSION AND COGNITIVE FUNCTION OF THE AD HAVE BEEN EMPHASIZED. NUTRIENTS AND OTHER BIOACTIVE NUTRIENTS ARE AMONG THE FACTORS THAT ARE EFFECTIVE IN AD. IN PARTICULAR, VITAMINS A, C AND E, VITAMINS B(1), B(6) AND B(12), FOLATE, MAGNESIUM, CHOLINE, INOSITOL, ANTHOCYANINS, ISOFLAVONES ETC. NUTRIENTS AND BIOACTIVE NUTRIENTS ARE KNOWN TO BE EFFECTIVE IN THE DEVELOPMENT OF AD. NUTRIENTS AND NUTRIENT COMPONENTS MAY ALSO HAVE AN EPIGENETIC EFFECT ON AD. AT THE SAME TIME, NUTRIENTS AND BIOACTIVE FOOD COMPONENTS SLOW DOWN THE PROGRESSION OF THE DISEASE. FOR THIS REASON, THE EFFECT OF NUTRIENTS AND FOOD COMPONENTS ON AD WAS EXAMINED IN THIS REVIEW. 2019 9 6436 35 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 10 4786 32 NUTRITION AND HEALTH DURING MID-LIFE: SEARCHING FOR SOLUTIONS AND MEETING CHALLENGES FOR THE AGING POPULATION. INTERACTIONS BETWEEN GENETIC (GENOME) AND ENVIRONMENTAL FACTORS (EPIGENOME) OPERATE DURING A PERSON'S ENTIRE LIFESPAN. THE AGING PROCESS IS ASSOCIATED WITH SEVERAL CELLULAR AND ORGANIC FUNCTIONAL ALTERATIONS THAT, AT THE END, CAUSE MULTI-ORGANIC CELL FAILURE. EPIGENETIC MECHANISMS OF AGING ARE MODIFIABLE BY APPROPRIATE PREVENTIVE ACTIONS MEDIATED BY SIRTUINS, CALORIC INPUT, DIET COMPONENTS, ADIPOSE TISSUE-RELATED INFLAMMATORY REACTIONS, AND PHYSICAL ACTIVITY. THE MEDITERRANEAN LIFESTYLE HAS BEEN FOR MANY MILLENNIA A DAILY HABIT FOR PEOPLE IN WESTERN CIVILIZATIONS LIVING AROUND THE MEDITERRANEAN SEA WHO WORKED INTENSIVELY AND SURVIVED WITH VERY FEW SEASONAL FOODS. A HIGH ADHERENCE TO THE TRADITIONAL MEDITERRANEAN DIET IS ASSOCIATED WITH LOW MORTALITY (HIGHER LONGEVITY) AND REDUCED RISK OF DEVELOPING CHRONIC DISEASES, INCLUDING CANCER, THE METABOLIC SYNDROME, DEPRESSION AND CARDIOVASCULAR AND NEURODEGENERATIVE DISEASES. REPORTS INDICATE THAT SOME DIETARY COMPONENTS, SUCH AS OLIVE OIL, ANTIOXIDANTS, OMEGA-3 AND -6 POLYUNSATURATED ACIDS, POLYPHENOLS AND FLAVONOIDS, MEDIATE BENEFICIAL ANTI-AGING EFFECTS (ANTI-CHRONIC DISEASES AND INCREASED LONGEVITY). EQUALLY, PHYSICAL ACTIVITY DISPLAYS A POSITIVE EFFECT, PRODUCING CALORIC CONSUMPTION AND REGULATION OF ADIPOSE AND PANCREATIC FUNCTION. THE PREDICTIVE STRENGTH OF SOME FOOD PATTERNS MAY BE A WAY OF DEVELOPING RECOMMENDATIONS FOR FOOD AND HEALTH POLICIES. THIS PAPER WILL DISCUSS SEVERAL WAYS OF IMPROVING HEALTH DURING MID-LIFE, FOCUSING ON CERTAIN GROUPS OF FUNCTIONAL FOODS AND HEALTHY HABITS WHICH MAY REDUCE OR PREVENT AGE-RELATED CHRONIC DISEASES. 2013 11 4778 33 NUTRACEUTICALS AND THE NETWORK OF OBESITY MODULATORS. OBESITY IS CONSIDERED AN INCREASINGLY WIDESPREAD DISEASE IN THE WORLD POPULATION, REGARDLESS OF AGE AND GENDER. GENETIC BUT ALSO LIFESTYLE-DEPENDENT CAUSES HAVE BEEN IDENTIFIED. NUTRITION AND PHYSICAL EXERCISE PLAY AN IMPORTANT ROLE, ESPECIALLY IN NON-GENETIC OBESITY. IN A THREE-COMPARTMENT MODEL, THE BODY IS DIVIDED INTO FAT MASS, FAT-FREE MASS AND WATER, AND OBESITY CAN BE CONSIDERED A CONDITION IN WHICH THE PERCENTAGE OF TOTAL FAT MASS IS IN EXCESS. PEOPLE WITH A HIGH BMI INDEX OR OVERWEIGHT USE SELF-MEDICATIONS, SUCH AS FOOD SUPPLEMENTS OR TEAS, WITH THE AIM TO PREVENT OR TREAT THEIR PROBLEM. UNFORTUNATELY, THERE ARE SEVERAL OBESITY MODULATORS THAT ACT BOTH ON THE PATHWAYS THAT PROMOTE ADIPOGENESIS AND THOSE THAT INHIBIT LIPOLYSIS. MOREOVER, THESE PATHWAYS INVOLVE DIFFERENT TISSUES AND ORGANS, SO IT IS VERY DIFFICULT TO IDENTIFY ANTI-OBESITY SUBSTANCES. A NETWORK OF FACTORS AND CELLS CONTRIBUTES TO THE ACCUMULATION OF FAT IN COMPLETELY DIFFERENT BODY DISTRICTS. THE IDENTIFICATION OF NATURAL ANTI-OBESITY AGENTS SHOULD CONSIDER THIS NETWORK, WHICH WE WOULD LIKE TO CALL "OBESOSOME". THE NUTRIGENOMIC, NUTRIGENETIC AND EPIGENETIC CONTRIBUTE TO MAKING THE IDENTIFICATION OF ACTIVE COMPOUNDS VERY DIFFICULT. THIS NARRATIVE REVIEW AIMS TO HIGHLIGHT NUTRACEUTICALS THAT, IN VITRO OR IN VIVO, SHOWED AN ANTI-OBESITY ACTIVITY OR WERE FOUND TO BE USEFUL IN THE CONTROL OF DYSFUNCTIONS WHICH ARE SECONDARY TO OBESITY. THE RESULTS SUGGEST THAT IT IS NOT POSSIBLE TO USE A SINGLE COMPOUND TO TREAT OBESITY, BUT THAT THE STUDIES HAVE TO BE ADDRESSED TOWARDS THE IDENTIFICATION OF MIXTURES OF NUTRACEUTICALS. 2022 12 4783 28 NUTRIGENOMICS IN PARKINSON'S DISEASE: DIVERSITY OF MODULATORY ACTIONS OF POLYPHENOLS ON EPIGENETIC EFFECTS INDUCED BY TOXINS. ALTHOUGH THE PATHOGENESIS OF PARKINSON'S DISEASE (PD) IS NOT COMPLETELY UNDERSTOOD, THERE IS A CONSENSUS THAT IT CAN BE CAUSED BY MULTIFACTORIAL MECHANISMS INVOLVING GENETIC SUSCEPTIBILITY, EPIGENETIC MODIFICATIONS INDUCED BY TOXINS AND MITOCHONDRIAL DYSFUNCTION. IN THE PAST 20 YEARS, GREAT EFFORTS HAVE BEEN MADE IN ORDER TO CLARIFY MOLECULAR MECHANISMS THAT ARE RISK FACTORS FOR THIS DISEASE, AS WELL AS TO IDENTIFY BIOACTIVE AGENTS FOR PREVENTION AND SLOWING DOWN OF ITS PROGRESSION. NUTRACEUTICAL PRODUCTS HAVE RECEIVED SUBSTANTIAL INTEREST DUE TO THEIR NUTRITIONAL, SAFE AND THERAPEUTIC EFFECTS ON SEVERAL CHRONIC DISEASES. THE AIM OF THIS REVIEW WAS TO GATHER THE MAIN EVIDENCE OF THE EPIGENETIC MECHANISMS INVOLVED IN THE NEUROPROTECTIVE EFFECTS OF PHENOLIC COMPOUNDS CURRENTLY UNDER INVESTIGATION FOR THE TREATMENT OF TOXIN-INDUCED PD. THESE STUDIES CONFIRM THAT THE NEUROPROTECTIVE ACTIONS OF POLYPHENOLS INVOLVE COMPLEX EPIGENETIC MODULATIONS, DEMONSTRATING THAT THE INTAKE OF THESE NATURAL COMPOUNDS CAN BE A PROMISING, LOW-COST, PHARMACOGENOMIC STRATEGY AGAINST THE DEVELOPMENT OF PD. 2023 13 3689 25 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 14 4044 26 MACROPHAGES IN OXIDATIVE STRESS AND MODELS TO EVALUATE THE ANTIOXIDANT FUNCTION OF DIETARY NATURAL COMPOUNDS. ANTIOXIDANT TESTING OF NATURAL PRODUCTS HAS ATTRACTED INCREASING INTEREST IN RECENT YEARS, MAINLY DUE TO THE FACT THAT AN ANTIOXIDANT-RICH DIET MIGHT PROVIDE HEALTH BENEFITS. ACTIVATED MACROPHAGES ARE A MAJOR SOURCE OF REACTIVE OXYGEN SPECIES, REACTIVE NITROGEN SPECIES, AND PEROXYNITRITE GENERATED THROUGH THE SO-CALLED RESPIRATORY BURST. CONSTITUTIVELY RELEASED PROINFLAMMATORY CYTOKINE, ESPECIALLY TUMOR NECROSIS FACTOR-ALPHA, TRIGGERS NUCLEAR FACTOR-KAPPAB, AND ACTIVATOR PROTEIN-1 TRANSLOCATION LEADING TO THE OVER PRODUCTION OF REACTIVE OXYGEN SPECIES AND REACTIVE NITROGEN SPECIES IN MACROPHAGES. ACTIVATION OF TRANSCRIPTION FACTORS IN THE LONG-LIVED TISSUE-RESIDENT MACROPHAGES AND/OR MONOCYTE-DERIVED MACROPHAGES, TRIGGER EPIGENETIC MODIFICATIONS LEADING TO THE PATHOGENESIS OF CHRONIC DISEASES. NUTRACEUTICALS INCLUDING LIPID RAFT STRUCTURE DISRUPTION AGENT, CHOLESTEROL DEPLETION AGENT, FARNESYLTRANSFERASE INHIBITOR, NUCLEAR FACTOR-KAPPAB BLOCKER (ALPHA,BETA-UNSATURATED CARBONYL COMPOUNDS), GLUCOCORTICOID RECEPTOR AGONIST, AND PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR-GAMMA AGONIST HAVE LONG BEEN USED TO INACTIVE MACROPHAGE. THE INHIBITION EFFECTS ON THE FORMATION OF NITRIC OXIDE, SUPEROXIDE, AND NITRITE PEROXIDE MAY BE RESPONSIBLE FOR THE ANTI-INFLAMMATORY FUNCTIONALITIES. ACTIVATED MACROPHAGE MODELS COULD BE USED TO IDENTIFY THE ACTIVE COMPONENTS FOR FUNCTIONAL DIETS DEVELOPMENT THROUGH A MULTIPLE TARGETS STRATEGY. 2017 15 617 26 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 16 2100 27 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 17 4396 28 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 18 1398 36 DIET, GUT MICROBIOME AND EPIGENETICS: EMERGING LINKS WITH INFLAMMATORY BOWEL DISEASES AND PROSPECTS FOR MANAGEMENT AND PREVENTION. INFLAMMATORY BOWEL DISEASES (IBD) REPRESENT A GROWING PUBLIC HEALTH CONCERN DUE TO INCREASING INCIDENCE WORLDWIDE. THE CURRENT NOTION ON THE PATHOGENESIS OF IBD IS THAT GENETICALLY SUSCEPTIBLE INDIVIDUALS DEVELOP INTOLERANCE TO DYSREGULATED GUT MICROFLORA (DYSBIOSIS) AND CHRONIC INFLAMMATION DEVELOPS AS A RESULT OF ENVIRONMENTAL TRIGGERS. AMONG THE ENVIRONMENTAL FACTORS ASSOCIATED WITH IBD, DIET PLAYS AN IMPORTANT ROLE IN MODULATING THE GUT MICROBIOME, INFLUENCING EPIGENETIC CHANGES, AND, THEREFORE, COULD BE APPLIED AS A THERAPEUTIC TOOL TO IMPROVE THE DISEASE COURSE. NEVERTHELESS, THE CURRENT DIETARY RECOMMENDATIONS FOR DISEASE PREVENTION AND MANAGEMENT ARE SCARCE AND HAVE WEAK EVIDENCE. THIS REVIEW SUMMARISES THE CURRENT KNOWLEDGE ON THE COMPLEX INTERACTIONS BETWEEN DIET, MICROBIOME AND EPIGENETICS IN IBD. WHEREAS AN OVERABUNDANCE OF CALORIES AND SOME MACRONUTRIENTS INCREASE GUT INFLAMMATION, SEVERAL MICRONUTRIENTS HAVE THE POTENTIAL TO MODULATE IT. IMMUNONUTRITION HAS EMERGED AS A NEW CONCEPT PUTTING FORWARD THE IMPORTANCE OF VITAMINS SUCH AS VITAMINS A, C, E, AND D, FOLIC ACID, BETA CAROTENE AND TRACE ELEMENTS SUCH AS ZINC, SELENIUM, MANGANESE AND IRON. HOWEVER, WHEN ASSESSED IN CLINICAL TRIALS, SPECIFIC MICRONUTRIENTS EXERTED A LIMITED BENEFIT. BEYOND NUTRIENTS, AN ANTI-INFLAMMATORY DIETARY PATTERN AS A COMPLEX INTERVENTION APPROACH HAS BECOME POPULAR IN RECENT YEARS. HENCE, EXCLUSIVE ENTERAL NUTRITION IN PAEDIATRIC CROHN'S DISEASE IS THE ONLY NUTRITIONAL INTERVENTION CURRENTLY RECOMMENDED AS A FIRST-LINE THERAPY. OTHER NUTRITIONAL INTERVENTIONS OR SPECIFIC DIETS INCLUDING THE SPECIFIC CARBOHYDRATE DIET (SCD), THE LOW FERMENTABLE OLIGOSACCHARIDES, DISACCHARIDES, MONOSACCHARIDES, AND POLYOL (FODMAP) DIET AND, MOST RECENTLY, THE MEDITERRANEAN DIET HAVE SHOWN STRONG ANTI-INFLAMMATORY PROPERTIES AND SHOW PROMISE FOR IMPROVING DISEASE SYMPTOMS. MORE WORK IS REQUIRED TO EVALUATE THE ROLE OF INDIVIDUAL FOOD COMPOUNDS AND COMPLEX NUTRITIONAL INTERVENTIONS WITH THE POTENTIAL TO DECREASE INFLAMMATION AS A MEANS OF PREVENTION AND MANAGEMENT OF IBD. 2017 19 4205 29 METABOLO-EPIGENETIC INTERPLAY PROVIDES TARGETED NUTRITIONAL INTERVENTIONS IN CHRONIC DISEASES AND AGEING. EPIGENETIC MODIFICATIONS ARE CHEMICAL MODIFICATIONS THAT AFFECT GENE EXPRESSION WITHOUT ALTERING DNA SEQUENCES. IN PARTICULAR, EPIGENETIC CHEMICAL MODIFICATIONS CAN OCCUR ON HISTONE PROTEINS -MAINLY ACETYLATION, METHYLATION-, AND ON DNA AND RNA MOLECULES -MAINLY METHYLATION-. ADDITIONAL MECHANISMS, SUCH AS RNA-MEDIATED REGULATION OF GENE EXPRESSION AND DETERMINANTS OF THE GENOMIC ARCHITECTURE CAN ALSO AFFECT GENE EXPRESSION. IMPORTANTLY, DEPENDING ON THE CELLULAR CONTEXT AND ENVIRONMENT, EPIGENETIC PROCESSES CAN DRIVE DEVELOPMENTAL PROGRAMS AS WELL AS FUNCTIONAL PLASTICITY. HOWEVER, MISBALANCED EPIGENETIC REGULATION CAN RESULT IN DISEASE, PARTICULARLY IN THE CONTEXT OF METABOLIC DISEASES, CANCER, AND AGEING. NON-COMMUNICABLE CHRONIC DISEASES (NCCD) AND AGEING SHARE COMMON FEATURES INCLUDING ALTERED METABOLISM, SYSTEMIC META-INFLAMMATION, DYSFUNCTIONAL IMMUNE SYSTEM RESPONSES, AND OXIDATIVE STRESS, AMONG OTHERS. IN THIS SCENARIO, UNBALANCED DIETS, SUCH AS HIGH SUGAR AND HIGH SATURATED FATTY ACIDS CONSUMPTION, TOGETHER WITH SEDENTARY HABITS, ARE RISK FACTORS IMPLICATED IN THE DEVELOPMENT OF NCCD AND PREMATURE AGEING. THE NUTRITIONAL AND METABOLIC STATUS OF INDIVIDUALS INTERACT WITH EPIGENETICS AT DIFFERENT LEVELS. THUS, IT IS CRUCIAL TO UNDERSTAND HOW WE CAN MODULATE EPIGENETIC MARKS THROUGH BOTH LIFESTYLE HABITS AND TARGETED CLINICAL INTERVENTIONS -INCLUDING FASTING MIMICKING DIETS, NUTRACEUTICALS, AND BIOACTIVE COMPOUNDS- WHICH WILL CONTRIBUTE TO RESTORE THE METABOLIC HOMEOSTASIS IN NCCD. HERE, WE FIRST DESCRIBE KEY METABOLITES FROM CELLULAR METABOLIC PATHWAYS USED AS SUBSTRATES TO "WRITE" THE EPIGENETIC MARKS; AND COFACTORS THAT MODULATE THE ACTIVITY OF THE EPIGENETIC ENZYMES; THEN, WE BRIEFLY SHOW HOW METABOLIC AND EPIGENETIC IMBALANCES MAY RESULT IN DISEASE; AND, FINALLY, WE SHOW SEVERAL EXAMPLES OF NUTRITIONAL INTERVENTIONS - DIET BASED INTERVENTIONS, BIOACTIVE COMPOUNDS, AND NUTRACEUTICALS- AND EXERCISE TO COUNTERACT EPIGENETIC ALTERATIONS. 2023 20 5052 38 PHARMACOLOGICAL TARGETING OF HEME OXYGENASE-1 IN OSTEOARTHRITIS. OSTEOARTHRITIS (OA) IS A COMMON AGING-ASSOCIATED DISEASE THAT CLINICALLY MANIFESTS AS JOINT PAIN, MOBILITY LIMITATIONS, AND COMPROMISED QUALITY OF LIFE. TODAY, OA TREATMENT IS LIMITED TO PAIN MANAGEMENT AND JOINT ARTHROPLASTY AT THE LATER STAGES OF DISEASE PROGRESSION. OA PATHOGENESIS IS PREDOMINANTLY MEDIATED BY OXIDATIVE DAMAGE TO JOINT CARTILAGE EXTRACELLULAR MATRIX AND LOCAL CELLS SUCH AS CHONDROCYTES, OSTEOCLASTS, OSTEOBLASTS, AND SYNOVIAL FIBROBLASTS. UNDER NORMAL CONDITIONS, CELLS PREVENT THE ACCUMULATION OF REACTIVE OXYGEN SPECIES (ROS) UNDER OXIDATIVELY STRESSFUL CONDITIONS THROUGH THEIR ADAPTIVE CYTOPROTECTIVE MECHANISMS. HEME OXYGENASE-1 (HO-1) IS AN IRON-DEPENDENT CYTOPROTECTIVE ENZYME THAT FUNCTIONS AS THE INDUCIBLE FORM OF HO. HO-1 AND ITS METABOLITES CARBON MONOXIDE AND BILIVERDIN CONTRIBUTE TOWARDS THE MAINTENANCE OF REDOX HOMEOSTASIS. HO-1 EXPRESSION IS PRIMARILY REGULATED AT THE TRANSCRIPTIONAL LEVEL THROUGH TRANSCRIPTIONAL FACTOR NUCLEAR FACTOR ERYTHROID 2 (NF-E2)-RELATED FACTOR 2 (NRF2), SPECIFICITY PROTEIN 1 (SP1), TRANSCRIPTIONAL REPRESSOR BTB-AND-CNC HOMOLOGY 1 (BACH1), AND EPIGENETIC REGULATION. SEVERAL STUDIES REPORT THAT HO-1 EXPRESSION CAN BE REGULATED USING VARIOUS ANTIOXIDATIVE FACTORS AND CHEMICAL COMPOUNDS, SUGGESTING THERAPEUTIC IMPLICATIONS IN OA PATHOGENESIS AS WELL AS IN THE WIDER CONTEXT OF JOINT DISEASE. HERE, WE REVIEW THE PROTECTIVE ROLE OF HO-1 IN OA WITH A FOCUS ON THE REGULATORY MECHANISMS THAT MEDIATE HO-1 ACTIVITY. 2021